Locally Advanced or Metastatic EGFR Sensitising Mutation Positive Non Small Cell Lung Cancer
Conditions
Keywords
Advanced Non-Small Cell Lung Cancer; EGFRm+; AZD9291; TKI; Phase III
Brief summary
To assess the efficacy and safety of AZD9291 versus a standard of care epidermal growth factor receptor tyrosine kinase inhibitor in patients with locally advanced or Metastatic Non Small Cell Lung Cancer
Detailed description
This is a Phase III, double-blind, randomised study assessing the efficacy and safety of AZD9291 (80 mg orally, once daily) versus a standard of care (SoC) Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) (either gefitinib \[250 mg orally, once daily\] or erlotinib \[150 mg orally, once daily\]) in patients with locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC) that is known to be EGFR sensitising mutation (EGFRm) positive, treatment-naïve and eligible for first-line treatment with an EGFR-TKI.
Interventions
DRUGAZD9291 80 mg/40 mg + placebo
The initial dose of AZD9291 80 mg once daily can be reduced to 40 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
DRUGPlacebo Erlotinib 150/100mg
The initial dose of Placebo Erlotinib 150 mg once daily can be reduced to Placebo 100 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
The initial dose of Placebo Gefitinib 250 mg once daily cannot be reduced. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
DRUGErlotinib 150/100 mg
The initial dose of Erlotinib 150mg once daily can be reduced to 10 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria. Following objective disease progression according to RECIST 1.1, as per investigator assessment, patients who were randomized to Standard of Care arm may have the option to receive open-label AZD9291 (crossover to active AZD9291).
DRUGGefitinib 250 mg
The initial dose of Gefitinib 250mg once daily cannot be reduced. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria. Following objective disease progression according to RECIST 1.1, as per investigator assessment, patients who were randomized to Standard of Care arm may have the option to receive open-label AZD9291 (crossover to active AZD9291).
DRUGPlacebo AZD9291 80 mg/ 40 mg
The initial dose of Placebo AZD9291 80 mg once daily can be reduced to Placebo AZD9291 40 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
Sponsors
AstraZeneca
Parexel
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female, aged at least 18 years. 2. Pathologically confirmed adenocarcinoma of the lung. 3. Locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy. 4. The tumour harbours one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R). 5. Mandatory provision of an unstained, archived tumour tissue sample in a quantity sufficient to allow for central analysis of EGFR mutation status. 6. Patients must be treatment-naïve for locally advanced or metastatic NSCLC and eligible to receive first-line treatment with gefitinib or erlotinib as selected by the participating centre. Prior adjuvant and neo-adjuvant therapy is permitted(chemotherapy, radiotherapy, investigational agents). 7. Provision of informed consent prior to any study specific procedures, sampling, and analysis. 8. World Health Organization Performance Status of 0 to 1 with no clinically significant deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks
Exclusion criteria
1. Treatment with any of the following: * Prior treatment with any systemic anti-cancer therapy for locally advanced/metastatic NSCLC. * Prior treatment with an EGFR-TKI. * Major surgery within 4 weeks of the first dose of study drug. * Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug. * Patients currently receiving medications or herbal supplements known to be potent inducers of cytochrome P450 (CYP) 3A4. * Alternative anti-cancer treatment * Treatment with an investigational drug within five half-lives of the compound or any of its related material. 2. Any concurrent and/or other active malignancy that has required treatment within 2 years of first dose of study drug. 3. Spinal cord compression, symptomatic and unstable brain metastases, except for those patients who have completed definitive therapy, are not on steroids, have a stable neurologic status for at least 2 weeks after completion of the definitive therapy and steroids. 4. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses; or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). 5. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of AZD9291. 6. Any of the following cardiac criteria: * Mean resting corrected QT interval (QTc) \>470 msec, obtained from 3 ECGs, using the screening clinic ECG machine-derived QTcF value. * Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG. * Any patient with any factors that increase the risk of QTc prolongation or risk of arrhythmic events or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval. 7. Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD. 8. Involvement in the planning and/or conduct of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Progression Free Survival (PFS) (Months) | At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomisation until progression | Progression-free survival was defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anti-cancer therapy prior to progression and was used to assess the efficacy of single agent osimertinib compared with SoC EGFR-TKI therapy as measured by PFS. The primary endpoint of PFS was based on Investigator assessment. |
| Percentage of Participants in Progression Free Survival at 6, 12, and 18 Months | At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomisation until progression | Progression-free survival was defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anti-cancer therapy prior to progression and was used to assess the efficacy of single agent osimertinib compared with SoC EGFR-TKI therapy as measured by PFS. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomisation until progression | ORR was defined as the number (%) of participants with measurable disease with at least 1 visit response of Complete response (CR) or Partial response (PR) and it was used to further assess the efficacy of osimertinib compared with SoC EGFR-TKI therapy. ORR was based on Investigator assessment. |
| Duration of Response (DoR) | At baseline and every 6 weeks for the first 18 months and then every 12 weeks until objective disease progression | Duration of response was defined as the time from the date of first documented response until the date of documented progression or death in the absence of disease progression and was used to further assess the efficacy of osimertinib compared with SoC EGFR-TKI therapy. |
| Disease Control Rate (DCR) | At baseline and every 6 weeks for the first 18 months and then every 12 weeks until objective disease progression | The DCR was defined as the percentage of participants who had a best overall response (BOR) of Complete response (CR), Partial response (PR) or Stable disease (SD) ≥6 weeks prior to any Progressive disease (PD) event and was used to further assess the efficacy of osimertinib compared with SoC EGFR-TKI therapy. |
| Depth of Response | At baseline and every 6 weeks for the first 18 months and then every 12 weeks until objective disease progression | The Depth of response was defined as the relative change in the sum of the longest diameters of Response Evaluation Criteria in Solid Tumors (RECIST) Target lesions (TLs) at the nadir, in the absence of new lesions (NLs) or progression of Non-target lesions (NTLs), compared to baseline and was used to further assess the efficacy of osimertinib compared with SoC EGFR-TKI therapy |
| Overall Survival (OS)- Number of Participants With an Event | From first dose to end of study or date of death from any cause, whichever comes first, assessed every 6 weeks (approximately 29 months) | Overall survival was defined as the time from the date of randomisation until death from any cause and was used to further assess the efficacy of osimertinib compared with SoC EGFR-TKI therapy |
| Plasma Concentrations of AZD9291 | Blood samples collected from each participant at pre-dose, 0.5 to 2 hours, and 3 to 5 hours post-dose on Day 1 Cycle 1, and every other cycle thereafter up to and including Cycle 13 (approximately 9 months) | To characterise the pharmacokinetics (PK) of osimertinib |
| Plasma Concentrations of Metabolites AZ5104 | Blood samples collected from each participant at pre-dose, 0.5 to 2 hours, and 3 to 5 hours post-dose on Day 1 Cycle 1, and every other cycle thereafter up to and including Cycle 13 (approximately 9 months) | To characterise the pharmacokinetics (PK) of osimertinib metabolite AZ5104. |
| Plasma Concentrations of Metabolite AZ7550 | Blood samples collected from each participant at pre-dose, 0.5 to 2 hours, and 3 to 5 hours post-dose on Day 1 Cycle 1, and every other cycle thereafter up to and including Cycle 13 (approximately 9 months) | To characterise the pharmacokinetics (PK) of osimertinib metabolite AZ7550. |
| Participants Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 Items (CTSQ-16 Questionnaire) | Questionnaire completed in cycle 2 and 3, prior to Week 6 scan (approximately 2 months) | The CTSQ-16 was a 16-item questionnaire measuring 3 domains related to participant's satisfaction with cancer therapy: Expectations of therapy, Feelings about side effects, and Satisfaction with therapy. Scores ranged from 0 to 100 for each domain, with a higher score associated with the best outcome on each domain. The three domains of interest were separately analysed using an ANCOVA stratified by race (Asian versus Non-Asian) and mutation type (Ex19del versus L858R). The results of the analyses were presented in terms of mean together with standard deviation. |
| Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Questionnaires completed at baseline, first 9 months, and at week 1, 2, 3, 4, 5, 6, 12, 18, 24, 30 and 36 | The EORTC QLQ-LC13 was a lung-cancer-specific module comprising 13 questions to assess lung cancer symptoms (cough, haemoptysis, dyspnoea, and site-specific pain); treatment related side-effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia); and pain medication. An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items. Higher scores on the global health status/QoL and functioning scales indicated better health status/QoL and function. Higher scores on the symptoms scales indicated greater symptom burden. The analysis was performed using a Mixed-effects model for repeated measures analysis on the change from baseline in PRO symptom score at each visit up to 9 months (281 days), including participants, treatment, visit and treatment by visit interaction as explanatory variables, the baseline PRO score as a covariate along with the baseline PRO score by visit interaction, using an unstructured covariance structure. |
| Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Questionnaires completed at baseline, first 9 months, and at week 6, 12, 18, 24, 30, and 36. | The EORTC QLQ-C30 cancer-specific questionnaire consisted of 30 questions, combined to produce 5 functional scales, 3 symptom scales, 6 individual items, and a global measure of health status/QoL. An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items, the functional scales, and the global health status/QoL scale in the EORTC QLQ-C30. Higher scores on the global health status and functioning scales indicated better health status/function. Higher scores on the symptoms scales indicated greater symptom burden. The analysis was performed using a Mixed-effects model for repeated measures analysis on the change from baseline in PRO symptom score at each visit up to 9 months (281 days), including participants, treatment, visit and treatment by visit interaction as explanatory variables, the baseline PRO score as a covariate along with the baseline PRO score by visit interaction, using an unstructured covariance structure. |
Countries
Australia, Belgium, Brazil, Bulgaria, Canada, China, Czechia, France, Germany, Hungary, Israel, Italy, Japan, Malaysia, Philippines, Poland, Portugal, Romania, Russia, South Korea, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United Kingdom, United States, Vietnam
Participant flow
Recruitment details
A total of 556 participants in Global cohort (out of 673 participants in Global and China cohorts) were randomized to treatment at 132 study centres in 29 countries. An additional 117 participants in 19 centres were enrolled into the China extension cohort only.
Pre-assignment details
During the 28 day screening period, participants were enrolled based on the presence in their tumour of at least 1 of the 2 most frequent Epidermal growth factor receptor (EGFR) mutations. At the time of enrolment, all participants were required to provide biopsy tissue for central testing of the Exon 19 deletion (Ex19del) and L858R mutations
Participants by arm
| Arm | Count |
|---|---|
| Global + China Extension Osimertinib Arm All participants who were enrolled in Osimertinib Arm for either the global or China Extension study. | 338 |
| Global + China Extension SoC EGFR-TKI Arm All participants who were enrolled in SoC EGFR-TKI Arm for either the Global or China Extension study | 335 |
| Total | 673 |
Baseline characteristics
| Characteristic | Global + China Extension Osimertinib Arm | Total | Global + China Extension SoC EGFR-TKI Arm |
|---|---|---|---|
| Age, Continuous China Cohort | 59.1 Years STANDARD_DEVIATION 9.66 | 59.0 Years STANDARD_DEVIATION 10.26 | 59.0 Years STANDARD_DEVIATION 10.94 |
| Age, Continuous Global cohort | 62.7 Years STANDARD_DEVIATION 10.7 | 63.0 Years STANDARD_DEVIATION 10.79 | 63.3 Years STANDARD_DEVIATION 10.9 |
| Race/Ethnicity, Customized Asian-Global Cohort | 77 Participants | 171 Participants | 94 Participants |
| Race/Ethnicity, Customized Chinese-China cohort | 71 Participants | 136 Participants | 65 Participants |
| Race/Ethnicity, Customized Chinese-Global Cohort | 32 Participants | 56 Participants | 24 Participants |
| Race/Ethnicity, Customized Hispanic or Latino-Global Cohort | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Japanese-Global Cohort | 65 Participants | 120 Participants | 55 Participants |
| Race/Ethnicity, Customized Missing-Global Cohort | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Other-Global Cohort | 103 Participants | 207 Participants | 104 Participants |
| Race (NIH/OMB) China Cohort American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) China Cohort Asian | 71 Participants | 136 Participants | 65 Participants |
| Race (NIH/OMB) China Cohort Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) China Cohort More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) China Cohort Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) China Cohort Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) China Cohort White | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Global Cohort American Indian or Alaska Native | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Global Cohort Asian | 174 Participants | 347 Participants | 173 Participants |
| Race (NIH/OMB) Global Cohort Black or African American | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Global Cohort More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Global Cohort Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Global Cohort Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Global Cohort White | 101 Participants | 201 Participants | 100 Participants |
| Sex: Female, Male China Cohort Female | 43 Participants | 89 Participants | 46 Participants |
| Sex: Female, Male China Cohort Male | 28 Participants | 47 Participants | 19 Participants |
| Sex: Female, Male Global cohort Female | 178 Participants | 350 Participants | 172 Participants |
| Sex: Female, Male Global cohort Male | 101 Participants | 206 Participants | 105 Participants |
| Smoking status Current smokers-China Cohort | 3 Participants | 7 Participants | 4 Participants |
| Smoking status Current smokers-Global Cohort | 8 Participants | 17 Participants | 9 Participants |
| Smoking status Former smokers-China Cohort | 15 Participants | 26 Participants | 11 Participants |
| Smoking status Former smokers-Global Cohort | 89 Participants | 182 Participants | 93 Participants |
| Smoking status Never smoked-China Cohort | 53 Participants | 103 Participants | 50 Participants |
| Smoking status Never smoked-Global Cohort | 182 Participants | 357 Participants | 175 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 155 / 279 | 166 / 277 | 45 / 71 | 44 / 65 |
| other Total, other adverse events | 273 / 279 | 271 / 277 | 70 / 71 | 64 / 65 |
| serious Total, serious adverse events | 74 / 279 | 76 / 277 | 25 / 71 | 12 / 65 |
Outcome results
Primary
Median Progression Free Survival (PFS) (Months)
Progression-free survival was defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anti-cancer therapy prior to progression and was used to assess the efficacy of single agent osimertinib compared with SoC EGFR-TKI therapy as measured by PFS. The primary endpoint of PFS was based on Investigator assessment.
Time frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomisation until progression
Population: The full analysis set (FAS) and China-only FAS. FAS included all randomized participants prior to the end of global recruitment. The China-only FAS included all China participants randomized in mainland-China as part of the global study and all additional China participants recruited in mainland China after global recruitment was completed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Osimertinib 80 mg (Global Cohort) | Median Progression Free Survival (PFS) (Months) | 18.9 Months |
| SoC EGFR-TKI (Global Cohort) | Median Progression Free Survival (PFS) (Months) | 10.2 Months |
| Osimertinib 80 mg (China Cohort) | Median Progression Free Survival (PFS) (Months) | 17.8 Months |
| SoC EGFR-TKI (China Cohort) | Median Progression Free Survival (PFS) (Months) | 9.8 Months |
p-value: <0.000195% CI: [0.37, 0.57]Log Rank
p-value: 0.006595% CI: [0.37, 0.85]Log Rank
Primary
Percentage of Participants in Progression Free Survival at 6, 12, and 18 Months
Progression-free survival was defined as the time from randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anti-cancer therapy prior to progression and was used to assess the efficacy of single agent osimertinib compared with SoC EGFR-TKI therapy as measured by PFS.
Time frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomisation until progression
Population: The full analysis set (FAS) and China-only FAS. FAS included all randomized participants prior to the end of global recruitment. The China-only FAS included all China participants randomized in mainland-China as part of the global study and all additional China participants recruited in mainland China after global recruitment was completed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Osimertinib 80 mg (Global Cohort) | Percentage of Participants in Progression Free Survival at 6, 12, and 18 Months | Progression free at 6 months (%) | 88.4 Percentage of Participants |
| Osimertinib 80 mg (Global Cohort) | Percentage of Participants in Progression Free Survival at 6, 12, and 18 Months | Progression free at 18 months (%) | 50.9 Percentage of Participants |
| Osimertinib 80 mg (Global Cohort) | Percentage of Participants in Progression Free Survival at 6, 12, and 18 Months | Progression free at 12 months (%) | 68.2 Percentage of Participants |
| SoC EGFR-TKI (Global Cohort) | Percentage of Participants in Progression Free Survival at 6, 12, and 18 Months | Progression free at 6 months (%) | 75.2 Percentage of Participants |
| SoC EGFR-TKI (Global Cohort) | Percentage of Participants in Progression Free Survival at 6, 12, and 18 Months | Progression free at 18 months (%) | 24.4 Percentage of Participants |
| SoC EGFR-TKI (Global Cohort) | Percentage of Participants in Progression Free Survival at 6, 12, and 18 Months | Progression free at 12 months (%) | 42.3 Percentage of Participants |
| Osimertinib 80 mg (China Cohort) | Percentage of Participants in Progression Free Survival at 6, 12, and 18 Months | Progression free at 12 months (%) | 67.3 Percentage of Participants |
| Osimertinib 80 mg (China Cohort) | Percentage of Participants in Progression Free Survival at 6, 12, and 18 Months | Progression free at 6 months (%) | 78.8 Percentage of Participants |
| Osimertinib 80 mg (China Cohort) | Percentage of Participants in Progression Free Survival at 6, 12, and 18 Months | Progression free at 18 months (%) | 46.9 Percentage of Participants |
| SoC EGFR-TKI (China Cohort) | Percentage of Participants in Progression Free Survival at 6, 12, and 18 Months | Progression free at 6 months (%) | 72.3 Percentage of Participants |
| SoC EGFR-TKI (China Cohort) | Percentage of Participants in Progression Free Survival at 6, 12, and 18 Months | Progression free at 18 months (%) | 25.8 Percentage of Participants |
| SoC EGFR-TKI (China Cohort) | Percentage of Participants in Progression Free Survival at 6, 12, and 18 Months | Progression free at 12 months (%) | 44.6 Percentage of Participants |
Secondary
Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13)
The EORTC QLQ-LC13 was a lung-cancer-specific module comprising 13 questions to assess lung cancer symptoms (cough, haemoptysis, dyspnoea, and site-specific pain); treatment related side-effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia); and pain medication. An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items. Higher scores on the global health status/QoL and functioning scales indicated better health status/QoL and function. Higher scores on the symptoms scales indicated greater symptom burden. The analysis was performed using a Mixed-effects model for repeated measures analysis on the change from baseline in PRO symptom score at each visit up to 9 months (281 days), including participants, treatment, visit and treatment by visit interaction as explanatory variables, the baseline PRO score as a covariate along with the baseline PRO score by visit interaction, using an unstructured covariance structure.
Time frame: Questionnaires completed at baseline, first 9 months, and at week 1, 2, 3, 4, 5, 6, 12, 18, 24, 30 and 36
Population: The full analysis set (FAS) and China-only FAS. FAS included all randomized participants prior to the end of global recruitment. The China-only FAS included all China participants randomized in mainland-China as part of the global study and all additional China participants recruited in mainland China after global recruitment was completed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 4 | -4.81 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 30 | -3.89 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 30 | -8.33 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 3 | -9.78 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 24 | -4.65 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, First 9 months | -6.62 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 36 | -11.49 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 5 | -12.98 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 6 | -11.88 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 12 | -13.36 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 18 | -12.31 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 18 | -6.79 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 24 | -11.34 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 30 | -10.34 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 36 | -2.88 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 36 | -7.94 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 12 | -7.28 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 6 | -4.99 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 1 | -1.93 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, First 9 months | -10.97 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, First 9 months | -4.04 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 24 | -7.72 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 1 | -3.46 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 1 | -6.90 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 5 | -7.33 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 2 | -3.94 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 3 | -3.99 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 2 | -5.94 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 4 | -7.45 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 5 | -3.51 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 2 | -9.04 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 6 | -4.51 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 3 | -7.17 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 12 | -3.83 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 18 | -4.97 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 4 | -11.25 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 6 | -4.45 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 36 | -5.58 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 30 | -3.68 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 4 | -13.36 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 1 | -4.26 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 36 | -2.04 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, First 9 months | -11.65 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, First 9 months | -6.41 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 2 | -9.52 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 3 | -10.24 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, First 9 months | -4.14 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 12 | -5.75 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 5 | -6.98 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 5 | -5.19 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 5 | -13.55 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 1 | -3.60 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 30 | -12.43 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 18 | -7.90 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 12 | -13.57 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 3 | -5.36 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 2 | -6.32 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 2 | -3.64 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 24 | -13.16 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 6 | -11.92 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 1 | -4.83 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 4 | -6.40 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 18 | -5.21 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 12 | -6.70 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 18 | -11.00 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 3 | -3.27 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 6 | -7.08 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 24 | -4.56 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 36 | -14.62 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 4 | -4.11 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 24 | -7.34 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 30 | -6.60 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 30 | -4.25 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 36 | -4.21 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 1 | -4.60 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 2 | -12.26 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 4 | -12.78 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 5 | -17.74 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 6 | -16.92 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 12 | -15.51 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 1 | -1.79 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 3 | -3.09 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 36 | -3.56 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, First 9 months | -4.87 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 1 | -1.61 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 2 | -2.27 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 4 | -5.35 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 5 | -5.72 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 6 | -4.83 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 12 | -5.38 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 18 | -7.67 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 24 | -7.59 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 30 | -5.81 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, First 9 months | -13.75 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 3 | -11.95 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 18 | -11.79 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 24 | -17.61 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 30 | -15.45 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 36 | -14.62 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, First 9 months | -2.79 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 2 | -4.76 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 3 | -0.76 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 4 | -2.13 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 5 | -0.62 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 6 | 0.94 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 12 | -3.71 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 18 | -4.40 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 24 | -5.66 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 24 | -5.67 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 12 | -6.67 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, First 9 months | -8.49 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 2 | -3.00 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 6 | -6.37 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 5 | -5.76 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 36 | -2.18 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 3 | -4.77 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 4 | -5.55 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 2 | -5.03 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 36 | -3.40 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 4 | -4.22 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 1 | 0.68 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, First 9 months | -4.82 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 24 | -3.15 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 30 | -9.35 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 5 | -6.82 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 24 | -14.92 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 18 | -7.48 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 6 | -6.26 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 18 | -9.44 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 12 | -8.04 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 30 | -4.02 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 12 | -5.13 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 5 | -9.20 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 6 | -10.58 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 2 | -3.73 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 4 | -10.32 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 3 | -5.55 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 36 | -8.55 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 3 | -5.56 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Cough, week 1 | -3.69 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 18 | -7.24 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, First 9 months | -4.74 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Dyspnoea, week 30 | -3.46 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ) Questionnaires Lung Cancer 13 (QLQ-LC13) | Pain in Chest, week 1 | -4.16 Unit on scale |
Secondary
Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30)
The EORTC QLQ-C30 cancer-specific questionnaire consisted of 30 questions, combined to produce 5 functional scales, 3 symptom scales, 6 individual items, and a global measure of health status/QoL. An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items, the functional scales, and the global health status/QoL scale in the EORTC QLQ-C30. Higher scores on the global health status and functioning scales indicated better health status/function. Higher scores on the symptoms scales indicated greater symptom burden. The analysis was performed using a Mixed-effects model for repeated measures analysis on the change from baseline in PRO symptom score at each visit up to 9 months (281 days), including participants, treatment, visit and treatment by visit interaction as explanatory variables, the baseline PRO score as a covariate along with the baseline PRO score by visit interaction, using an unstructured covariance structure.
Time frame: Questionnaires completed at baseline, first 9 months, and at week 6, 12, 18, 24, 30, and 36.
Population: The full analysis set (FAS) and China-only FAS. FAS included all randomized participants prior to the end of global recruitment. The China-only FAS included all China participants randomized in mainland-China as part of the global study and all additional China participants recruited in mainland China after global recruitment was completed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Appetite Loss, week 36 | -6.90 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Appetite Loss, First 9 months | -6.15 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Fatigue, week 36 | -5.47 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Fatigue, week 18 | -6.83 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Appetite Loss, week 24 | -7.14 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Fatigue, week 30 | -5.19 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Fatigue, week 24 | -6.18 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Fatigue, First 9 months | -5.48 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Appetite Loss, week 18 | -7.27 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Fatigue, week 6 | -4.13 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Appetite Loss, week 30 | -4.50 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Appetite Loss, week 12 | -6.52 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Appetite Loss, week 6 | -4.54 Unit on scale |
| Osimertinib 80 mg (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Fatigue, week 12 | -5.11 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Fatigue, week 12 | -6.52 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Fatigue, week 30 | -3.26 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Appetite Loss, week 18 | -6.84 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Appetite Loss, week 24 | -5.08 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Fatigue, week 6 | -5.78 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Fatigue, First 9 months | -4.72 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Fatigue, week 18 | -5.77 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Fatigue, week 24 | -4.96 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Fatigue, week 36 | -2.00 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Appetite Loss, First 9 months | -5.64 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Appetite Loss, week 6 | -5.67 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Appetite Loss, week 12 | -6.95 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Appetite Loss, week 30 | -4.17 Unit on scale |
| SoC EGFR-TKI (Global Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Appetite Loss, week 36 | -5.15 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Appetite Loss, week 12 | 1.58 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Appetite Loss, First 9 months | 1.18 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Fatigue, week 36 | -6.78 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Appetite Loss, week 36 | 0.98 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Fatigue, week 12 | -5.40 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Appetite Loss, week 24 | -2.26 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Appetite Loss, week 6 | 3.20 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Appetite Loss, week 30 | 2.19 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Appetite Loss, week 18 | 1.42 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Fatigue, week 24 | -8.92 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Fatigue, week 6 | -1.73 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Fatigue, week 18 | -6.64 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Fatigue, week 30 | -4.43 Unit on scale |
| Osimertinib 80 mg (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Fatigue, First 9 months | -5.65 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Fatigue, week 30 | -6.31 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Fatigue, week 36 | -3.46 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Appetite Loss, First 9 months | -1.73 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Fatigue, week 6 | -6.81 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Appetite Loss, week 30 | -1.83 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Appetite Loss, week 6 | -6.27 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Appetite Loss, week 12 | -1.44 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Fatigue, First 9 months | -5.79 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Appetite Loss, week 18 | -4.43 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Appetite Loss, week 36 | 3.36 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Appetite Loss, week 24 | 0.24 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Fatigue, week 18 | -7.90 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Fatigue, week 24 | -3.87 Unit on scale |
| SoC EGFR-TKI (China Cohort) | Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 Items (EORTC QLQ-C30) | Fatigue, week 12 | -6.36 Unit on scale |
Secondary
Depth of Response
The Depth of response was defined as the relative change in the sum of the longest diameters of Response Evaluation Criteria in Solid Tumors (RECIST) Target lesions (TLs) at the nadir, in the absence of new lesions (NLs) or progression of Non-target lesions (NTLs), compared to baseline and was used to further assess the efficacy of osimertinib compared with SoC EGFR-TKI therapy
Time frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks until objective disease progression
Population: The full analysis set (FAS) and China-only FAS. FAS included all randomized participants prior to the end of global recruitment. The China-only FAS included all China participants randomized in mainland-China as part of the global study and all additional China participants recruited in mainland China after global recruitment was completed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Osimertinib 80 mg (Global Cohort) | Depth of Response | -52.36 percentage of change | Standard Deviation 25.065 |
| SoC EGFR-TKI (Global Cohort) | Depth of Response | -45.66 percentage of change | Standard Deviation 28.27 |
| Osimertinib 80 mg (China Cohort) | Depth of Response | -49.17 percentage of change | Standard Deviation 24.303 |
| SoC EGFR-TKI (China Cohort) | Depth of Response | -42.92 percentage of change | Standard Deviation 26.814 |
p-value: 0.002595% CI: [-11.205, -2.403]Regression, Linear
p-value: 0.134895% CI: [-15.246, 2.072]Regression, Linear
Secondary
Disease Control Rate (DCR)
The DCR was defined as the percentage of participants who had a best overall response (BOR) of Complete response (CR), Partial response (PR) or Stable disease (SD) ≥6 weeks prior to any Progressive disease (PD) event and was used to further assess the efficacy of osimertinib compared with SoC EGFR-TKI therapy.
Time frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks until objective disease progression
Population: The full analysis set (FAS) and China-only FAS. FAS included all randomized participants prior to the end of global recruitment. The China-only FAS included all China participants randomized in mainland-China as part of the global study and all additional China participants recruited in mainland China after global recruitment was completed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Osimertinib 80 mg (Global Cohort) | Disease Control Rate (DCR) | 97.1 Percentage of participants |
| SoC EGFR-TKI (Global Cohort) | Disease Control Rate (DCR) | 92.4 Percentage of participants |
| Osimertinib 80 mg (China Cohort) | Disease Control Rate (DCR) | 97.2 Percentage of participants |
| SoC EGFR-TKI (China Cohort) | Disease Control Rate (DCR) | 95.4 Percentage of participants |
p-value: 0.01195% CI: [1.25, 6.78]Regression, Logistic
p-value: 0.577295% CI: [0.27, 12.98]Regression, Logistic
Secondary
Duration of Response (DoR)
Duration of response was defined as the time from the date of first documented response until the date of documented progression or death in the absence of disease progression and was used to further assess the efficacy of osimertinib compared with SoC EGFR-TKI therapy.
Time frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks until objective disease progression
Population: The full analysis set (FAS) and China-only FAS. FAS included all randomized participants prior to the end of global recruitment. The China-only FAS included all China participants randomized in mainland-China as part of the global study and all additional China participants recruited in mainland China after global recruitment was completed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Osimertinib 80 mg (Global Cohort) | Duration of Response (DoR) | 17.2 Months |
| SoC EGFR-TKI (Global Cohort) | Duration of Response (DoR) | 8.5 Months |
| Osimertinib 80 mg (China Cohort) | Duration of Response (DoR) | 16.4 Months |
| SoC EGFR-TKI (China Cohort) | Duration of Response (DoR) | 10.9 Months |
p-value: 0.013395% CI: [1.21, 5.09]Regression, Linear
p-value: <0.000195% CI: [1.68, 3.08]Regression, Linear
Secondary
Objective Response Rate (ORR)
ORR was defined as the number (%) of participants with measurable disease with at least 1 visit response of Complete response (CR) or Partial response (PR) and it was used to further assess the efficacy of osimertinib compared with SoC EGFR-TKI therapy. ORR was based on Investigator assessment.
Time frame: At baseline and every 6 weeks for the first 18 months and then every 12 weeks relative to randomisation until progression
Population: The full analysis set (FAS) and China-only FAS. FAS included all randomized participants prior to the end of global recruitment. The China-only FAS included all China participants randomized in mainland-China as part of the global study and all additional China participants recruited in mainland China after global recruitment was completed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Osimertinib 80 mg (Global Cohort) | Objective Response Rate (ORR) | 76.7 Percentage of participants |
| SoC EGFR-TKI (Global Cohort) | Objective Response Rate (ORR) | 69.0 Percentage of participants |
| Osimertinib 80 mg (China Cohort) | Objective Response Rate (ORR) | 76.1 Percentage of participants |
| SoC EGFR-TKI (China Cohort) | Objective Response Rate (ORR) | 70.8 Percentage of participants |
p-value: 0.48595% CI: [0.61, 2.84]Regression, Logistic
p-value: 0.03695% CI: [1.03, 2.22]Regression, Logistic
Secondary
Overall Survival (OS)- Number of Participants With an Event
Overall survival was defined as the time from the date of randomisation until death from any cause and was used to further assess the efficacy of osimertinib compared with SoC EGFR-TKI therapy
Time frame: From first dose to end of study or date of death from any cause, whichever comes first, assessed every 6 weeks (approximately 29 months)
Population: The full analysis set (FAS) and China-only FAS. FAS included all randomized participants prior to the end of global recruitment. The China-only FAS included all China participants randomized in mainland-China as part of the global study and all additional China participants recruited in mainland China after global recruitment was completed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Osimertinib 80 mg (Global Cohort) | Overall Survival (OS)- Number of Participants With an Event | Death | 155 Participants |
| Osimertinib 80 mg (Global Cohort) | Overall Survival (OS)- Number of Participants With an Event | Terminated prior to death | 20 Participants |
| Osimertinib 80 mg (Global Cohort) | Overall Survival (OS)- Number of Participants With an Event | Still in survival follow-up | 104 Participants |
| SoC EGFR-TKI (Global Cohort) | Overall Survival (OS)- Number of Participants With an Event | Death | 166 Participants |
| SoC EGFR-TKI (Global Cohort) | Overall Survival (OS)- Number of Participants With an Event | Terminated prior to death | 25 Participants |
| SoC EGFR-TKI (Global Cohort) | Overall Survival (OS)- Number of Participants With an Event | Still in survival follow-up | 86 Participants |
| Osimertinib 80 mg (China Cohort) | Overall Survival (OS)- Number of Participants With an Event | Still in survival follow-up | 25 Participants |
| Osimertinib 80 mg (China Cohort) | Overall Survival (OS)- Number of Participants With an Event | Death | 45 Participants |
| Osimertinib 80 mg (China Cohort) | Overall Survival (OS)- Number of Participants With an Event | Terminated prior to death | 1 Participants |
| SoC EGFR-TKI (China Cohort) | Overall Survival (OS)- Number of Participants With an Event | Death | 44 Participants |
| SoC EGFR-TKI (China Cohort) | Overall Survival (OS)- Number of Participants With an Event | Terminated prior to death | 4 Participants |
| SoC EGFR-TKI (China Cohort) | Overall Survival (OS)- Number of Participants With an Event | Still in survival follow-up | 17 Participants |
p-value: 0.046295% CI: [0.6409, 0.9963]Log Rank
p-value: 0.441695% CI: [0.5568, 1.291]Log Rank
Secondary
Participants Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 Items (CTSQ-16 Questionnaire)
The CTSQ-16 was a 16-item questionnaire measuring 3 domains related to participant's satisfaction with cancer therapy: Expectations of therapy, Feelings about side effects, and Satisfaction with therapy. Scores ranged from 0 to 100 for each domain, with a higher score associated with the best outcome on each domain. The three domains of interest were separately analysed using an ANCOVA stratified by race (Asian versus Non-Asian) and mutation type (Ex19del versus L858R). The results of the analyses were presented in terms of mean together with standard deviation.
Time frame: Questionnaire completed in cycle 2 and 3, prior to Week 6 scan (approximately 2 months)
Population: The full analysis set (FAS) and China-only FAS. FAS included all randomized participants prior to the end of global recruitment. The China-only FAS included all China participants randomized in mainland-China as part of the global study and all additional China participants recruited in mainland China after global recruitment was completed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Osimertinib 80 mg (Global Cohort) | Participants Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 Items (CTSQ-16 Questionnaire) | Expectations with Therapy, Week 6 | 76.3 Unit on scale | Standard Deviation 20.58 |
| Osimertinib 80 mg (Global Cohort) | Participants Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 Items (CTSQ-16 Questionnaire) | Expectations with Therapy, Week 3 | 74.1 Unit on scale | Standard Deviation 22.42 |
| Osimertinib 80 mg (Global Cohort) | Participants Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 Items (CTSQ-16 Questionnaire) | Feelings about Side-Effects, Week 3 | 74.5 Unit on scale | Standard Deviation 17.22 |
| Osimertinib 80 mg (Global Cohort) | Participants Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 Items (CTSQ-16 Questionnaire) | Feelings about Side-Effects, Week 6 | 74.6 Unit on scale | Standard Deviation 19.83 |
| Osimertinib 80 mg (Global Cohort) | Participants Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 Items (CTSQ-16 Questionnaire) | Satisfaction with Therapy, Week 3 | 84.4 Unit on scale | Standard Deviation 12.88 |
| Osimertinib 80 mg (Global Cohort) | Participants Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 Items (CTSQ-16 Questionnaire) | Satisfaction with Therapy, Week 6 | 84.2 Unit on scale | Standard Deviation 13.94 |
| SoC EGFR-TKI (Global Cohort) | Participants Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 Items (CTSQ-16 Questionnaire) | Satisfaction with Therapy, Week 6 | 84.6 Unit on scale | Standard Deviation 12.38 |
| SoC EGFR-TKI (Global Cohort) | Participants Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 Items (CTSQ-16 Questionnaire) | Feelings about Side-Effects, Week 6 | 69.9 Unit on scale | Standard Deviation 20.73 |
| SoC EGFR-TKI (Global Cohort) | Participants Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 Items (CTSQ-16 Questionnaire) | Expectations with Therapy, Week 3 | 70.3 Unit on scale | Standard Deviation 21.85 |
| SoC EGFR-TKI (Global Cohort) | Participants Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 Items (CTSQ-16 Questionnaire) | Feelings about Side-Effects, Week 3 | 69.1 Unit on scale | Standard Deviation 20.96 |
| SoC EGFR-TKI (Global Cohort) | Participants Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 Items (CTSQ-16 Questionnaire) | Expectations with Therapy, Week 6 | 74.0 Unit on scale | Standard Deviation 19.46 |
| SoC EGFR-TKI (Global Cohort) | Participants Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 Items (CTSQ-16 Questionnaire) | Satisfaction with Therapy, Week 3 | 82.6 Unit on scale | Standard Deviation 13.6 |
| Osimertinib 80 mg (China Cohort) | Participants Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 Items (CTSQ-16 Questionnaire) | Expectations with Therapy, Week 6 | 82.2 Unit on scale | Standard Deviation 17.88 |
| Osimertinib 80 mg (China Cohort) | Participants Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 Items (CTSQ-16 Questionnaire) | Feelings about Side-Effects, Week 3 | 73.3 Unit on scale | Standard Deviation 19.89 |
| Osimertinib 80 mg (China Cohort) | Participants Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 Items (CTSQ-16 Questionnaire) | Feelings about Side-Effects, Week 6 | 69.0 Unit on scale | Standard Deviation 24.46 |
| Osimertinib 80 mg (China Cohort) | Participants Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 Items (CTSQ-16 Questionnaire) | Satisfaction with Therapy, Week 6 | 87.4 Unit on scale | Standard Deviation 13.29 |
| Osimertinib 80 mg (China Cohort) | Participants Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 Items (CTSQ-16 Questionnaire) | Satisfaction with Therapy, Week 3 | 87.2 Unit on scale | Standard Deviation 12.14 |
| Osimertinib 80 mg (China Cohort) | Participants Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 Items (CTSQ-16 Questionnaire) | Expectations with Therapy, Week 3 | 77.1 Unit on scale | Standard Deviation 20.6 |
| SoC EGFR-TKI (China Cohort) | Participants Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 Items (CTSQ-16 Questionnaire) | Expectations with Therapy, Week 3 | 79.2 Unit on scale | Standard Deviation 18.58 |
| SoC EGFR-TKI (China Cohort) | Participants Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 Items (CTSQ-16 Questionnaire) | Satisfaction with Therapy, Week 3 | 86.6 Unit on scale | Standard Deviation 11.07 |
| SoC EGFR-TKI (China Cohort) | Participants Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 Items (CTSQ-16 Questionnaire) | Satisfaction with Therapy, Week 6 | 87.2 Unit on scale | Standard Deviation 12.06 |
| SoC EGFR-TKI (China Cohort) | Participants Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 Items (CTSQ-16 Questionnaire) | Feelings about Side-Effects, Week 6 | 69.7 Unit on scale | Standard Deviation 20.99 |
| SoC EGFR-TKI (China Cohort) | Participants Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 Items (CTSQ-16 Questionnaire) | Expectations with Therapy, Week 6 | 82.6 Unit on scale | Standard Deviation 17.95 |
| SoC EGFR-TKI (China Cohort) | Participants Reported Outcome by Cancer Therapy Satisfaction Questionnaire 16 Items (CTSQ-16 Questionnaire) | Feelings about Side-Effects, Week 3 | 72.5 Unit on scale | Standard Deviation 17.46 |
Secondary
Plasma Concentrations of AZD9291
To characterise the pharmacokinetics (PK) of osimertinib
Time frame: Blood samples collected from each participant at pre-dose, 0.5 to 2 hours, and 3 to 5 hours post-dose on Day 1 Cycle 1, and every other cycle thereafter up to and including Cycle 13 (approximately 9 months)
Population: The pharmacokinetic analysis set (osimertinib arm only) was defined as participants in the FAS who had at least 1 evaluable PK concentration and who had no detectable pre-dose osimertinib concentrations above the lower limit of quantitation (LLQ) on Cycle 1 Day 1.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 1 Day 1-0.5 - 2 hours | 4.9487 Nano moles | Geometric Coefficient of Variation 1173.3679 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 7 Day 1-3-5 hours | 475.6587 Nano moles | Geometric Coefficient of Variation 41.5778 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 3 Day 1, 0.5 - 2 hours | 397.7406 Nano moles | Geometric Coefficient of Variation 45.8548 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 9 Day 1-Predose | 359.5284 Nano moles | Geometric Coefficient of Variation 47.0592 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 5 Day 1, 0.5 - 2 hours | 369.0696 Nano moles | Geometric Coefficient of Variation 51.3284 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 9 Day 1-0.5-2 hours | 363.0106 Nano moles | Geometric Coefficient of Variation 48.3837 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 3 Day 1, 3 - 5 hours | 512.4012 Nano moles | Geometric Coefficient of Variation 44.0653 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 9 Day 1-3-5 hours | 485.6006 Nano moles | Geometric Coefficient of Variation 46.6459 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 1 Day 1-Predose | NA Nano moles | — |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 11 Day 1-Predose | 354.5330 Nano moles | Geometric Coefficient of Variation 44.4308 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 1 Day 1-3 - 5 hours | 129.3340 Nano moles | Geometric Coefficient of Variation 171.2983 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 11 Day 1-0.5 -2 hours | 367.7450 Nano moles | Geometric Coefficient of Variation 45.2003 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 5 Day 1, 3-5 hours | 485.8142 Nano moles | Geometric Coefficient of Variation 47.2759 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 11 Day 1-3-5 hours | 476.4472 Nano moles | Geometric Coefficient of Variation 44.4457 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 5 Day 1, Predose | 358.5487 Nano moles | Geometric Coefficient of Variation 53.8212 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 13 Day 1-Predose | 369.9834 Nano moles | Geometric Coefficient of Variation 40.1071 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 7 Day 1-Predose | 347.6176 Nano moles | Geometric Coefficient of Variation 47.7442 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 13 Day 1-0.5 -2 hours | 371.4157 Nano moles | Geometric Coefficient of Variation 42.9794 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 3 Day 1- Predose | 394.3489 Nano moles | Geometric Coefficient of Variation 43.9296 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 13 Day 1-3-5 hours | 496.6866 Nano moles | Geometric Coefficient of Variation 40.8757 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 7 Day 1-0.5 - 2 hours | 357.8529 Nano moles | Geometric Coefficient of Variation 45.0713 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 13 Day 1-3-5 hours | 499.0220 Nano moles | Geometric Coefficient of Variation 62.5485 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 1 Day 1-Predose | NA Nano moles | — |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 5 Day 1, Predose | 419.5893 Nano moles | Geometric Coefficient of Variation 63.2507 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 1 Day 1-3 - 5 hours | 131.5669 Nano moles | Geometric Coefficient of Variation 120.5979 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 3 Day 1- Predose | 441.5606 Nano moles | Geometric Coefficient of Variation 55.0039 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 3 Day 1, 0.5 - 2 hours | 441.7343 Nano moles | Geometric Coefficient of Variation 60.0626 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 3 Day 1, 3 - 5 hours | 553.8090 Nano moles | Geometric Coefficient of Variation 60.9883 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 5 Day 1, 0.5 - 2 hours | 426.8197 Nano moles | Geometric Coefficient of Variation 60.3841 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 5 Day 1, 3-5 hours | 570.7729 Nano moles | Geometric Coefficient of Variation 61.4401 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 7 Day 1-Predose | 397.5857 Nano moles | Geometric Coefficient of Variation 54.9006 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 7 Day 1-0.5 - 2 hours | 411.6170 Nano moles | Geometric Coefficient of Variation 49.4107 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 7 Day 1-3-5 hours | 530.7212 Nano moles | Geometric Coefficient of Variation 56.5184 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 9 Day 1-Predose | 383.2238 Nano moles | Geometric Coefficient of Variation 67.7153 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 9 Day 1-0.5-2 hours | 395.2179 Nano moles | Geometric Coefficient of Variation 71.5532 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 9 Day 1-3-5 hours | 490.5964 Nano moles | Geometric Coefficient of Variation 70.3383 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 11 Day 1-Predose | 410.4023 Nano moles | Geometric Coefficient of Variation 66.2329 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 11 Day 1-0.5 -2 hours | 415.2427 Nano moles | Geometric Coefficient of Variation 64.6174 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 11 Day 1-3-5 hours | 528.8081 Nano moles | Geometric Coefficient of Variation 68.4645 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 13 Day 1-Predose | 404.2678 Nano moles | Geometric Coefficient of Variation 62.0291 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 13 Day 1-0.5 -2 hours | 393.1688 Nano moles | Geometric Coefficient of Variation 62.1053 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of AZD9291 | Cycle 1 Day 1-0.5 - 2 hours | 5.0249 Nano moles | Geometric Coefficient of Variation 816.7305 |
Secondary
Plasma Concentrations of Metabolite AZ7550
To characterise the pharmacokinetics (PK) of osimertinib metabolite AZ7550.
Time frame: Blood samples collected from each participant at pre-dose, 0.5 to 2 hours, and 3 to 5 hours post-dose on Day 1 Cycle 1, and every other cycle thereafter up to and including Cycle 13 (approximately 9 months)
Population: The pharmacokinetic analysis set (osimertinib arm only) was defined as participants in the FAS who had at least 1 evaluable PK concentration and who had no detectable pre-dose osimertinib concentrations above the lower limit of quantitation (LLQ) on Cycle 1 Day 1.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 3 Day 1, 0.5 - 2 hours | 46.0045 Nano moles | Geometric Coefficient of Variation 45.9584 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 7 Day 1, 0.5-2 hours | 46.3540 Nano moles | Geometric Coefficient of Variation 49.0845 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 1 Day 1, Predose | NA Nano moles | — |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 7 Day 1,3-5 hours | 52.3533 Nano moles | Geometric Coefficient of Variation 47.6489 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 3 Day 1, 3 - 5 hours | 51.7182 Nano moles | Geometric Coefficient of Variation 45.324 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 9 Day 1, Predose | 49.6058 Nano moles | Geometric Coefficient of Variation 45.505 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 1 Day 1, 3 - 5 hours | 1.8610 Nano moles | Geometric Coefficient of Variation 147.4624 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 9 Day 1, 0.5-2 hours | 49.9381 Nano moles | Geometric Coefficient of Variation 46.4568 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 5 Day 1, Predose | 44.4537 Nano moles | Geometric Coefficient of Variation 54.9882 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 9 Day 1, 3-5 hours | 56.5354 Nano moles | Geometric Coefficient of Variation 45.6736 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 13 Day 1, 3-5 hours | 61.6053 Nano moles | Geometric Coefficient of Variation 42.2947 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 11 Day 1, Predose | 50.9710 Nano moles | Geometric Coefficient of Variation 46.884 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 5 Day 1, 0.5 - 2 hours | 45.2186 Nano moles | Geometric Coefficient of Variation 51.6418 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 11 Day 1, 0.5- 2 hours | 51.9773 Nano moles | Geometric Coefficient of Variation 45.3186 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 3 Day 1, Predose | 46.1286 Nano moles | Geometric Coefficient of Variation 45.1082 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 11 Day 1, 3- 5 hours | 57.6986 Nano moles | Geometric Coefficient of Variation 48.2382 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 5 Day 1, 3-5 hours | 51.4018 Nano moles | Geometric Coefficient of Variation 51.3627 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 13 Day 1, Predose | 54.5238 Nano moles | Geometric Coefficient of Variation 43.8481 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 1 Day 1, 0.5 - 2 hours | 0.1437 Nano moles | Geometric Coefficient of Variation 168.2087 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 13 Day 1, 0.5-2 hours | 54.1224 Nano moles | Geometric Coefficient of Variation 43.7869 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 7 Day 1, Predose | 46.2912 Nano moles | Geometric Coefficient of Variation 49.8713 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 13 Day 1, 3-5 hours | 63.3365 Nano moles | Geometric Coefficient of Variation 46.3082 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 1 Day 1, Predose | NA Nano moles | — |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 1 Day 1, 0.5 - 2 hours | NA Nano moles | — |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 1 Day 1, 3 - 5 hours | 2.1876 Nano moles | Geometric Coefficient of Variation 123.6012 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 3 Day 1, Predose | 55.9958 Nano moles | Geometric Coefficient of Variation 50.5705 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 3 Day 1, 0.5 - 2 hours | 55.6754 Nano moles | Geometric Coefficient of Variation 53.0925 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 3 Day 1, 3 - 5 hours | 62.3493 Nano moles | Geometric Coefficient of Variation 53.5513 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 5 Day 1, Predose | 53.0434 Nano moles | Geometric Coefficient of Variation 52.2936 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 5 Day 1, 0.5 - 2 hours | 53.1901 Nano moles | Geometric Coefficient of Variation 51.5506 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 5 Day 1, 3-5 hours | 62.5218 Nano moles | Geometric Coefficient of Variation 51.0627 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 7 Day 1, Predose | 53.4167 Nano moles | Geometric Coefficient of Variation 50.8399 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 7 Day 1, 0.5-2 hours | 54.3942 Nano moles | Geometric Coefficient of Variation 46.1253 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 7 Day 1,3-5 hours | 61.9004 Nano moles | Geometric Coefficient of Variation 51.6117 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 9 Day 1, Predose | 54.8207 Nano moles | Geometric Coefficient of Variation 50.2534 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 9 Day 1, 0.5-2 hours | 55.2437 Nano moles | Geometric Coefficient of Variation 52.5736 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 9 Day 1, 3-5 hours | 60.8933 Nano moles | Geometric Coefficient of Variation 50.3474 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 11 Day 1, Predose | 56.4643 Nano moles | Geometric Coefficient of Variation 51.2351 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 11 Day 1, 0.5- 2 hours | 57.4778 Nano moles | Geometric Coefficient of Variation 47.3639 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 11 Day 1, 3- 5 hours | 65.3053 Nano moles | Geometric Coefficient of Variation 49.6916 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 13 Day 1, Predose | 56.0666 Nano moles | Geometric Coefficient of Variation 51.2464 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolite AZ7550 | Cycle 13 Day 1, 0.5-2 hours | 56.8750 Nano moles | Geometric Coefficient of Variation 47.4338 |
Secondary
Plasma Concentrations of Metabolites AZ5104
To characterise the pharmacokinetics (PK) of osimertinib metabolite AZ5104.
Time frame: Blood samples collected from each participant at pre-dose, 0.5 to 2 hours, and 3 to 5 hours post-dose on Day 1 Cycle 1, and every other cycle thereafter up to and including Cycle 13 (approximately 9 months)
Population: The pharmacokinetic analysis set (osimertinib arm only) was defined as participants in the FAS who had at least 1 evaluable PK concentration and who had no detectable pre-dose osimertinib concentrations above the lower limit of quantitation (LLQ) on Cycle 1 Day 1.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 7 Day 1- Predose | 38.3847 Nano moles | Geometric Coefficient of Variation 50.0861 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 3 Day 1, 0.5 - 2 hours | 42.7434 Nano moles | Geometric Coefficient of Variation 52.8557 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 7 Day 1, 0.5-2 hours | 38.5301 Nano moles | Geometric Coefficient of Variation 49.6296 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 1 Day 1 Predose | NA Nano moles | — |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 7 Day 1, 3-5 hours | 44.4670 Nano moles | Geometric Coefficient of Variation 48.473 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 3 Day 1, 3 - 5 hours | 48.3547 Nano moles | Geometric Coefficient of Variation 50.4286 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 9 Day 1, Predose | 40.1230 Nano moles | Geometric Coefficient of Variation 47.0682 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 1 Day 1-3 - 5 hours | 3.9399 Nano moles | Geometric Coefficient of Variation 153.7651 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 9 Day 1, 0.5-2 hours | 40.4987 Nano moles | Geometric Coefficient of Variation 47.6483 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 5 Day 1, Predose | 39.3718 Nano moles | Geometric Coefficient of Variation 56.6226 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 9 Day 1, 3-5 hours | 46.0310 Nano moles | Geometric Coefficient of Variation 44.6875 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 13 Day 1, Predose | 40.4356 Nano moles | Geometric Coefficient of Variation 47.2671 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 11 Day 1, Predose | 38.3859 Nano moles | Geometric Coefficient of Variation 48.5351 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 5 Day 1, 0.5 - 2 hours | 39.4145 Nano moles | Geometric Coefficient of Variation 55.3468 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 11 Day 1, 0.5-2 hours | 38.7620 Nano moles | Geometric Coefficient of Variation 48.1414 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 3 Day 1-Predose | 42.9123 Nano moles | Geometric Coefficient of Variation 50.241 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 11 Day 1, 3-5 hours | 43.9135 Nano moles | Geometric Coefficient of Variation 50.6779 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 13 Day 1, 0.5- 2 hours | 40.1116 Nano moles | Geometric Coefficient of Variation 46.3929 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 5 Day 1, 3-5 hours | 45.6842 Nano moles | Geometric Coefficient of Variation 54.3876 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 13 Day 1, 3-5 hours | 45.9083 Nano moles | Geometric Coefficient of Variation 44.8309 |
| Osimertinib 80 mg (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 1 Day 1-0.5 - 2 hours | 0.1542 Nano moles | Geometric Coefficient of Variation 230.5161 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 13 Day 1, 3-5 hours | 61.7426 Nano moles | Geometric Coefficient of Variation 51.2924 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 13 Day 1, Predose | 55.1162 Nano moles | Geometric Coefficient of Variation 54.3493 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 1 Day 1 Predose | NA Nano moles | — |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 1 Day 1-0.5 - 2 hours | NA Nano moles | — |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 1 Day 1-3 - 5 hours | 6.3053 Nano moles | Geometric Coefficient of Variation 123.9308 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 3 Day 1-Predose | 56.8319 Nano moles | Geometric Coefficient of Variation 51.0378 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 3 Day 1, 0.5 - 2 hours | 55.9947 Nano moles | Geometric Coefficient of Variation 59.1318 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 3 Day 1, 3 - 5 hours | 64.0621 Nano moles | Geometric Coefficient of Variation 54.2058 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 5 Day 1, Predose | 56.0330 Nano moles | Geometric Coefficient of Variation 57.5022 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 5 Day 1, 0.5 - 2 hours | 55.3767 Nano moles | Geometric Coefficient of Variation 55.9096 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 5 Day 1, 3-5 hours | 63.9216 Nano moles | Geometric Coefficient of Variation 56.4249 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 7 Day 1- Predose | 52.5786 Nano moles | Geometric Coefficient of Variation 51.0588 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 7 Day 1, 0.5-2 hours | 52.7638 Nano moles | Geometric Coefficient of Variation 47.4797 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 7 Day 1, 3-5 hours | 60.6201 Nano moles | Geometric Coefficient of Variation 50.6931 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 9 Day 1, Predose | 54.4349 Nano moles | Geometric Coefficient of Variation 51.3447 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 9 Day 1, 0.5-2 hours | 54.7158 Nano moles | Geometric Coefficient of Variation 54.6783 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 9 Day 1, 3-5 hours | 60.4649 Nano moles | Geometric Coefficient of Variation 52.6147 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 11 Day 1, Predose | 56.4782 Nano moles | Geometric Coefficient of Variation 59.1303 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 11 Day 1, 0.5-2 hours | 57.4095 Nano moles | Geometric Coefficient of Variation 57.0891 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 13 Day 1, 0.5- 2 hours | 54.3858 Nano moles | Geometric Coefficient of Variation 49.9148 |
| SoC EGFR-TKI (Global Cohort) | Plasma Concentrations of Metabolites AZ5104 | Cycle 11 Day 1, 3-5 hours | 65.1943 Nano moles | Geometric Coefficient of Variation 58.5043 |