Non-small Cell Lung Cancer
Conditions
Brief summary
This randomized active-controlled multicenter Phase III open-label study will evaluate and compare between treatment groups the efficacy of alectinib versus chemotherapy in participants with ALK-positive advanced NSCLC who were previously treated with chemotherapy and crizotinib, as measured by investigator-assessed progression-free survival (PFS) and to evaluate and compare between treatment groups the central nervous system (CNS) objective response rate (C-ORR) in participants with measurable CNS metastases at baseline, as assessed by an Independent Review Committee (IRC).
Interventions
DRUGAlectinib
Participants will receive oral alectinib at a dose of 600 mg twice daily, taken with food until disease progression, unacceptable toxicity, withdrawal of consent or death.
DRUGDocetaxel
Participants will receive docetaxel at a dose of 75 mg/m\^2 of body surface area intravenously every 3 weeks, until disease progression, unacceptable toxicity, withdrawal of consent or death.
DRUGPemetrexed
Participants will receive pemetrexed at a dose of 500 mg/m\^2 of body surface area intravenously every 3 weeks, until disease progression, unacceptable toxicity, withdrawal of consent or death.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC that is ALK-positive. ALK positivity must have been determined by a validated fluorescence in situ hybridization (FISH) test (recommended probe, Vysis ALK Break-Apart Probe) or a validated immunohistochemistry (IHC) test (recommended antibody, clone D5F3) * Participant had received two prior systemic lines of therapy, which must have included one line of platinum-based chemotherapy and one line of crizotinib * Prior CNS or leptomeningeal metastases allowed if asymptomatic * Participants with symptomatic CNS metastases for whom radiotherapy is not an option will be allowed to participate in this study * Measurable disease by RECIST Version 1.1 prior to the administration of study treatment * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 * For all females of childbearing potential, a negative pregnancy test must be obtained within 3 days before starting study treatment
Exclusion criteria
* Participants with a previous malignancy within the past 3 years are excluded (other than curatively treated basal cell carcinoma of the skin, early gastrointestinal \[GI\] cancer by endoscopic resection or in situ carcinoma of the cervix) * Participants who have received any previous ALK inhibitor other than crizotinib * Any GI disorder that may affect absorption of oral medications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator | Randomization to first documented disease progression, death from any cause, or study end (up to 33 months) | PFS was defined as the time from randomization to the first documented disease progression, as determined using RECIST v1.1, or death from any cause, whichever occurred first. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 millimeter (mm) and the appearance of new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS Using RECIST Version 1.1 as Assessed by IRC | Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD) | PFS was defined as the time from randomization to the first documented disease progression, as determined using RECIST v1.1, or death from any cause, whichever occurred first. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm and the appearance of new lesions. This outcome measure was assessed as part of the primary analysis and was not repeated during final analysis. |
| Percentage of Participants With Objective Response of CR or PR Using RECIST Version 1.1 as Assessed by Investigator and IRC | Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD) | ORR was defined as the percentage of participants who attained CR or PR. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. The IRC assessment was part of the primary analysis and was not repeated during final analysis. |
| Percentage of Participants With Disease Control Using RECIST Version 1.1 as Assessed by Investigator and IRC | Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD) | Disease control rate (DCR) was defined as the percentage of participants who attained CR, PR, or stable disease (SD) of at least 5 weeks. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters, SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters since the treatment started. The IRC assessment was part of the primary analysis and was not repeated during final analysis. |
| Duration of Response (DOR) Using RECIST Version 1.1 as Assessed by Investigator and IRC | From the first documented CR or PR to the first documented disease progression, death, or study end (up to 33 months) | DOR was defined as the time from when response (CR or PR) was first documented to first documented disease progression or death, whichever occurred first. DOR was evaluated for participants who had a best overall response (BOR) of CR or PR. The IRC assessment was part of the primary analysis and was not repeated during final analysis. |
| PFS in C-ITT Population Using RECIST Version 1.1 as Assessed by Investigator and IRC | Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD) | PFS was defined as the time from randomization to the first documented disease progression, as determined using RECIST v1.1, or death from any cause, whichever occurred first. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm and the appearance of new lesions. This outcome measure assessment was part of the primary analysis and was not repeated during final analysis. |
| Time to CNS Progression in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC | Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD) | Time to CNS progression was defined as the time from randomization until radiographic evidence of CNS progression. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm and the appearance of new lesions. This outcome measure assessment was part of the primary analysis and was not repeated during final analysis. |
| Percentage of Participants With Disease Control in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC | From first documented CR, PR, or SD lasting at least 5 weeks through study end (up to 33 months) | Disease Control Rate (DCR) was defined as the percentage of participants who attained CR, PR, or stable disease (SD) of at least 5 weeks. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters, SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters since the treatment started. |
| Percentage of Participants With ORR in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC | Baseline through study end (up to 33 months) | ORR was defined as the percentage of participants who attained CR or PR. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. |
| Duration of Response for Lesions in the CNS (C-DOR) Using RECIST Version 1.1 as Assessed by IRC | From the first documented CR or PR to the first documented disease progression, death, or study end (up to 33 months) | DOR was defined as the time from when response (CR or PR) was first documented to first documented disease progression or death, whichever occurred first. C-DOR was defined in a similar way for lesions in the CNS, taking into account all lesions in the body. DOR was evaluated for participants who had a BOR of CR or PR. |
| Overall Survival (OS) | Randomization to death from any cause, through study end (up to 33 months) | Overall survival (OS) was defined as the time from randomization to death from any cause. OS was confounded by cross-over of participants to the alectinib arm. |
| Plasma Concentration of Alectinib | Predose (2 hours) at Baseline, Week 3 and Week 6 | — |
| Percentage of Participants With CNS Objective Response Rate (ORR) With Measurable CNS Metastases at Baseline Using RECIST Version 1.1 as Assessed By IRC | Baseline through study end (up to 33 months) | Overall response rate in subjects with confirmed CNS response (C-ORR) was defined as the percentage of subjects who attained Complete Response (CR) or Partial Response (PR) for lesions in the CNS. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. |
| Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Baseline through Week 138 | Percentage of participants who filled out an EORTC QLQ-C30 questionnaire at a visit. The EORTC QLQ-C30 questionnaire consisted of 30 questions generating five functional scores (physical, role, cognitive, emotional, and social); a global health status/global quality of life scale score; three symptom scale scores (fatigue, pain, and nausea and vomiting); and six stand alone one-item scores that capture additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and perceived financial burden. |
| Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Baseline through Week 138 | Percentage of participants who filled out an EORTC QLQ-LC13 questionnaire at a visit. The EORTC QLQ-LC13 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. |
| Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time | Baseline through Week 60 | Percentage of participants who filled out an ED-5D-5L questionnaire at a visit. EQ-5D-5L: A generic preference-based health utility measure that provides a single index value for health status. The instrument consists of two parts. The first part, health-state classification, contains five dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. |
| Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for ITT Population | Baseline through study end (up to 33 months) | TTD in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea \[single item and multi-item scales\] chest pain \[single item\], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-LC13. |
| Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for C-ITT Population | Baseline through study end (up to 33 months) | TTD in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea \[single item and multi-item scales\] chest pain \[single item\], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-LC13. |
| Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for ITT Population | Baseline through study end (up to 33 months) | TTD in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea \[single item and multi-item scales\] chest pain \[single item\], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-C30. |
| Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for C-ITT Population | Baseline through study end (up to 33 months) | TTD in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea \[single item and multi-item scales\] chest pain \[single item\], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-C30. |
| TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for C-ITT Population | Baseline through study end (up to 33 months) | TTD for a composite of three symptoms (cough, dyspnea, chest pain) in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for any component of the composite of the three following symptoms \[cough, dyspnea \[multi-item subscales QLQ-LC13\] and chest pain\]) as measured by the EORTC QLQ-LC13. |
| TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for ITT Population | Baseline through study end (up to 33 months) | TTD for a composite of three symptoms (cough, dyspnea, chest pain) in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for any component of the composite of the three following symptoms \[cough, dyspnea \[multi-item subscales QLQ-LC13\] and chest pain\]) as measured by the EORTC QLQ-LC13. |
| Percentage of Participants With Adverse Events (AEs) | Baseline through study end (up to 33 months) | An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. |
| Plasma Concentration of Alectinib Metabolite | Predose (2 hours) at Baseline, Week 3 and Week 6 | — |
Countries
Belgium, Bulgaria, France, Germany, Hong Kong, Hungary, Italy, Norway, Poland, Portugal, Russia, Slovakia, South Korea, Spain, Turkey (Türkiye)
Participant flow
Recruitment details
The study recruited participants with Anaplastic Lymphoma Kinase (ALK)-positive advanced Non-Small Cell Lung Cancer (NSCLC) in 13 countries from November 2015 to March 2017.
Pre-assignment details
A total of 119 participants were enrolled and randomized into the study: 79 participants in the alectinib arm, and 40 participants in the chemotherapy arm.
Participants by arm
| Arm | Count |
|---|---|
| Experimental: Alectinib Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death. | 79 |
| Active Comparator: Premetrexed/Docetaxel Participants received chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously. | 40 |
| Total | 119 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 32 | 16 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Progression of disease | 1 | 0 |
| Overall Study | Study Termination by Sponsor | 1 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 6 |
Baseline characteristics
| Characteristic | Active Comparator: Premetrexed/Docetaxel | Total | Experimental: Alectinib |
|---|---|---|---|
| Age, Continuous | 58.8 years STANDARD_DEVIATION 10.5 | 56.0 years STANDARD_DEVIATION 12.4 | 54.6 years STANDARD_DEVIATION 13 |
| Race/Ethnicity, Customized Asian | 8 Participants | 14 Participants | 6 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 4 Participants | 9 Participants | 5 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 34 Participants | 102 Participants | 68 Participants |
| Race/Ethnicity, Customized Not reported | 1 Participants | 5 Participants | 4 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 5 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 32 Participants | 99 Participants | 67 Participants |
| Sex: Female, Male Female | 20 Participants | 53 Participants | 33 Participants |
| Sex: Female, Male Male | 20 Participants | 66 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 26 / 77 | 4 / 37 |
| other Total, other adverse events | 57 / 77 | 31 / 37 |
| serious Total, serious adverse events | 20 / 77 | 7 / 37 |
Outcome results
Primary
Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator
PFS was defined as the time from randomization to the first documented disease progression, as determined using RECIST v1.1, or death from any cause, whichever occurred first. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 millimeter (mm) and the appearance of new lesions.
Time frame: Randomization to first documented disease progression, death from any cause, or study end (up to 33 months)
Population: ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental: Alectinib | Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator | 10.9 months |
| Active Comparator: Premetrexed/Docetaxel | Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator | 1.4 months |
p-value: <0.00195% CI: [0.12, 0.33]Stratified log-rank test
Secondary
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time
Percentage of participants who filled out an EORTC QLQ-C30 questionnaire at a visit. The EORTC QLQ-C30 questionnaire consisted of 30 questions generating five functional scores (physical, role, cognitive, emotional, and social); a global health status/global quality of life scale score; three symptom scale scores (fatigue, pain, and nausea and vomiting); and six stand alone one-item scores that capture additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and perceived financial burden.
Time frame: Baseline through Week 138
Population: ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Baseline | 92.4 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 60 | 100 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 66 | 89.7 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 72 | 88.9 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 78 | 84.6 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 84 | 78.3 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 90 | 88.9 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 96 | 93.8 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 102 | 84.6 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 108 | 100 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 114 | 83.3 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 120 | 100 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 126 | 100 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 132 | 100 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 138 | 100 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 3 | 96.1 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 6 | 97.2 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 12 | 95.5 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 18 | 88.5 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 24 | 91.1 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 30 | 96.2 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 36 | 89.8 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 42 | 95.3 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 48 | 100 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 54 | 97.1 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Baseline | 85.0 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 36 | 66.7 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 3 | 83.3 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 66 | 100 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 6 | 60.0 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 42 | 66.7 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 12 | 80.0 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 60 | 100 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 18 | 50.0 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 48 | 100 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 24 | 100 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 72 | 100 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 30 | 66.7 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time | Treatment - Week 54 | 100 percentage of participants |
Secondary
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time
Percentage of participants who filled out an EORTC QLQ-LC13 questionnaire at a visit. The EORTC QLQ-LC13 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis.
Time frame: Baseline through Week 138
Population: ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Baseline | 92.4 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 60 | 100 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 66 | 89.7 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 72 | 88.9 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 78 | 84.6 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 84 | 78.3 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 90 | 88.9 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 96 | 100 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 102 | 84.6 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 108 | 100 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 114 | 83.3 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 120 | 80.0 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 126 | 100 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 132 | 100 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 138 | 100 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 3 | 96.1 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 6 | 97.2 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 12 | 95.5 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 18 | 88.5 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 24 | 91.1 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 30 | 96.2 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 36 | 87.8 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 42 | 95.3 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 48 | 100 percentage of participants |
| Experimental: Alectinib | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 54 | 97.1 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Baseline | 82.5 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 36 | 66.7 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 3 | 83.3 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 66 | 100 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 6 | 63.3 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 42 | 66.7 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 12 | 80.0 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 60 | 100 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 18 | 50.0 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 48 | 100 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 24 | 100 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 72 | 100 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 30 | 66.7 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time | Treatment - Week 54 | 100 percentage of participants |
Secondary
Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time
Percentage of participants who filled out an ED-5D-5L questionnaire at a visit. EQ-5D-5L: A generic preference-based health utility measure that provides a single index value for health status. The instrument consists of two parts. The first part, health-state classification, contains five dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
Time frame: Baseline through Week 60
Population: ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Experimental: Alectinib | Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time | Treatment - Week 6 | 91.9 percentage of participants |
| Experimental: Alectinib | Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time | Treatment - Week 12 | 86.8 percentage of participants |
| Experimental: Alectinib | Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time | Treatment - Week 18 | 72.1 percentage of participants |
| Experimental: Alectinib | Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time | Treatment - Week 24 | 82.4 percentage of participants |
| Experimental: Alectinib | Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time | Treatment - Week 30 | 80 percentage of participants |
| Experimental: Alectinib | Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time | Treatment - Week 36 | 80 percentage of participants |
| Experimental: Alectinib | Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time | Treatment - Week 42 | 91.7 percentage of participants |
| Experimental: Alectinib | Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time | Treatment - Week 48 | 62.5 percentage of participants |
| Experimental: Alectinib | Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time | Treatment - Week 54 | 100 percentage of participants |
| Experimental: Alectinib | Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time | Treatment - Week 60 | 50 percentage of participants |
| Experimental: Alectinib | Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time | Treatment - Week 0 | 88.9 percentage of participants |
| Experimental: Alectinib | Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time | Treatment - Week 3 | 86.6 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time | Treatment - Week 12 | 80 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time | Treatment - Week 42 | 50 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time | Treatment - Week 18 | 66.7 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time | Treatment - Week 3 | 78.8 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time | Treatment - Week 24 | 100 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time | Treatment - Week 48 | 0 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time | Treatment - Week 30 | 66.7 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time | Treatment - Week 0 | 82.9 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time | Treatment - Week 36 | 50 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time | Treatment - Week 6 | 58.6 percentage of participants |
Secondary
Duration of Response (DOR) Using RECIST Version 1.1 as Assessed by Investigator and IRC
DOR was defined as the time from when response (CR or PR) was first documented to first documented disease progression or death, whichever occurred first. DOR was evaluated for participants who had a best overall response (BOR) of CR or PR. The IRC assessment was part of the primary analysis and was not repeated during final analysis.
Time frame: From the first documented CR or PR to the first documented disease progression, death, or study end (up to 33 months)
Population: ITT population included all participants randomized in the study, irrespective of whether or not they received study drug. Number analyzed indicates number of participants with a BOR of CR or PR.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Experimental: Alectinib | Duration of Response (DOR) Using RECIST Version 1.1 as Assessed by Investigator and IRC | Assessed by Investigator | 12.0 months |
| Experimental: Alectinib | Duration of Response (DOR) Using RECIST Version 1.1 as Assessed by Investigator and IRC | Assessed by IRC | 9.7 months |
| Active Comparator: Premetrexed/Docetaxel | Duration of Response (DOR) Using RECIST Version 1.1 as Assessed by Investigator and IRC | Assessed by Investigator | 2.7 months |
| Active Comparator: Premetrexed/Docetaxel | Duration of Response (DOR) Using RECIST Version 1.1 as Assessed by Investigator and IRC | Assessed by IRC | NA months |
Secondary
Duration of Response for Lesions in the CNS (C-DOR) Using RECIST Version 1.1 as Assessed by IRC
DOR was defined as the time from when response (CR or PR) was first documented to first documented disease progression or death, whichever occurred first. C-DOR was defined in a similar way for lesions in the CNS, taking into account all lesions in the body. DOR was evaluated for participants who had a BOR of CR or PR.
Time frame: From the first documented CR or PR to the first documented disease progression, death, or study end (up to 33 months)
Population: C-ITT included participants in ITT population with CNS metastasis at baseline (as per IRC assessment). Number analyzed indicates number of participants with a BOR of CR or PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental: Alectinib | Duration of Response for Lesions in the CNS (C-DOR) Using RECIST Version 1.1 as Assessed by IRC | 13.9 months |
| Active Comparator: Premetrexed/Docetaxel | Duration of Response for Lesions in the CNS (C-DOR) Using RECIST Version 1.1 as Assessed by IRC | NA months |
Secondary
Overall Survival (OS)
Overall survival (OS) was defined as the time from randomization to death from any cause. OS was confounded by cross-over of participants to the alectinib arm.
Time frame: Randomization to death from any cause, through study end (up to 33 months)
Population: ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental: Alectinib | Overall Survival (OS) | 27.8 months |
| Active Comparator: Premetrexed/Docetaxel | Overall Survival (OS) | NA months |
Secondary
Percentage of Participants With Adverse Events (AEs)
An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time frame: Baseline through study end (up to 33 months)
Population: Safety (SAF) population included all participants who received at least one dose of any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental: Alectinib | Percentage of Participants With Adverse Events (AEs) | 89.6 Percentage of Participants |
| Active Comparator: Premetrexed/Docetaxel | Percentage of Participants With Adverse Events (AEs) | 89.2 Percentage of Participants |
Secondary
Percentage of Participants With CNS Objective Response Rate (ORR) With Measurable CNS Metastases at Baseline Using RECIST Version 1.1 as Assessed By IRC
Overall response rate in subjects with confirmed CNS response (C-ORR) was defined as the percentage of subjects who attained Complete Response (CR) or Partial Response (PR) for lesions in the CNS. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.
Time frame: Baseline through study end (up to 33 months)
Population: ITT population with measurable CNS metastasis (mc-ITT) included all participants in ITT population with measurable CNS metastasis at baseline (as per IRC).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental: Alectinib | Percentage of Participants With CNS Objective Response Rate (ORR) With Measurable CNS Metastases at Baseline Using RECIST Version 1.1 as Assessed By IRC | 66.7 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Percentage of Participants With CNS Objective Response Rate (ORR) With Measurable CNS Metastases at Baseline Using RECIST Version 1.1 as Assessed By IRC | 0.0 percentage of participants |
Comparison: 95% confidence interval of the difference (alectinib - chemotherapy) computed using Hauck-Anderson approach.p-value: <0.00195% CI: [0.39, 0.86]Chi-squared
Secondary
Percentage of Participants With Disease Control in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC
Disease Control Rate (DCR) was defined as the percentage of participants who attained CR, PR, or stable disease (SD) of at least 5 weeks. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters, SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters since the treatment started.
Time frame: From first documented CR, PR, or SD lasting at least 5 weeks through study end (up to 33 months)
Population: C-ITT included participants in ITT population with CNS metastasis at baseline (as per IRC assessment).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental: Alectinib | Percentage of Participants With Disease Control in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC | 82.7 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Percentage of Participants With Disease Control in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC | 25.0 percentage of participants |
Secondary
Percentage of Participants With Disease Control Using RECIST Version 1.1 as Assessed by Investigator and IRC
Disease control rate (DCR) was defined as the percentage of participants who attained CR, PR, or stable disease (SD) of at least 5 weeks. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters, SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters since the treatment started. The IRC assessment was part of the primary analysis and was not repeated during final analysis.
Time frame: Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
Population: ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Experimental: Alectinib | Percentage of Participants With Disease Control Using RECIST Version 1.1 as Assessed by Investigator and IRC | Assessed by Investigator | 86.1 percentage of participants |
| Experimental: Alectinib | Percentage of Participants With Disease Control Using RECIST Version 1.1 as Assessed by Investigator and IRC | Assessed by IRC | 76.4 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Percentage of Participants With Disease Control Using RECIST Version 1.1 as Assessed by Investigator and IRC | Assessed by Investigator | 25.0 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Percentage of Participants With Disease Control Using RECIST Version 1.1 as Assessed by Investigator and IRC | Assessed by IRC | 48.6 percentage of participants |
Secondary
Percentage of Participants With Objective Response of CR or PR Using RECIST Version 1.1 as Assessed by Investigator and IRC
ORR was defined as the percentage of participants who attained CR or PR. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. The IRC assessment was part of the primary analysis and was not repeated during final analysis.
Time frame: Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
Population: ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Experimental: Alectinib | Percentage of Participants With Objective Response of CR or PR Using RECIST Version 1.1 as Assessed by Investigator and IRC | Assessed by Investigator | 50.6 percentage of participants |
| Experimental: Alectinib | Percentage of Participants With Objective Response of CR or PR Using RECIST Version 1.1 as Assessed by Investigator and IRC | Assessed by IRC | 36.1 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Percentage of Participants With Objective Response of CR or PR Using RECIST Version 1.1 as Assessed by Investigator and IRC | Assessed by Investigator | 2.5 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Percentage of Participants With Objective Response of CR or PR Using RECIST Version 1.1 as Assessed by Investigator and IRC | Assessed by IRC | 11.4 percentage of participants |
Secondary
Percentage of Participants With ORR in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC
ORR was defined as the percentage of participants who attained CR or PR. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.
Time frame: Baseline through study end (up to 33 months)
Population: C-ITT included participants in ITT population with CNS metastasis at baseline (as per IRC assessment).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Experimental: Alectinib | Percentage of Participants With ORR in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC | 48.1 percentage of participants |
| Active Comparator: Premetrexed/Docetaxel | Percentage of Participants With ORR in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC | 0.0 percentage of participants |
Secondary
PFS in C-ITT Population Using RECIST Version 1.1 as Assessed by Investigator and IRC
PFS was defined as the time from randomization to the first documented disease progression, as determined using RECIST v1.1, or death from any cause, whichever occurred first. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm and the appearance of new lesions. This outcome measure assessment was part of the primary analysis and was not repeated during final analysis.
Time frame: Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
Population: Intent-to-treat population with CNS metastasis (C-ITT) included participants in ITT population with CNS metastasis at baseline (as per IRC assessment).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Experimental: Alectinib | PFS in C-ITT Population Using RECIST Version 1.1 as Assessed by Investigator and IRC | Assessed by Investigator | 9.7 months |
| Experimental: Alectinib | PFS in C-ITT Population Using RECIST Version 1.1 as Assessed by Investigator and IRC | Assessed by IRC | 8.1 months |
| Active Comparator: Premetrexed/Docetaxel | PFS in C-ITT Population Using RECIST Version 1.1 as Assessed by Investigator and IRC | Assessed by Investigator | 1.4 months |
| Active Comparator: Premetrexed/Docetaxel | PFS in C-ITT Population Using RECIST Version 1.1 as Assessed by Investigator and IRC | Assessed by IRC | 1.5 months |
Secondary
PFS Using RECIST Version 1.1 as Assessed by IRC
PFS was defined as the time from randomization to the first documented disease progression, as determined using RECIST v1.1, or death from any cause, whichever occurred first. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm and the appearance of new lesions. This outcome measure was assessed as part of the primary analysis and was not repeated during final analysis.
Time frame: Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
Population: ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental: Alectinib | PFS Using RECIST Version 1.1 as Assessed by IRC | 7.1 months |
| Active Comparator: Premetrexed/Docetaxel | PFS Using RECIST Version 1.1 as Assessed by IRC | 1.6 months |
Secondary
Plasma Concentration of Alectinib
Time frame: Predose (2 hours) at Baseline, Week 3 and Week 6
Population: The Pharmacokinetic (PK) Evaluable Population included all participants who received any dose of alectinib and who had at least one post-baseline PK sample available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Experimental: Alectinib | Plasma Concentration of Alectinib | 559 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 48 |
Secondary
Plasma Concentration of Alectinib Metabolite
Time frame: Predose (2 hours) at Baseline, Week 3 and Week 6
Population: The PK Evaluable Population included all participants who received any dose of alectinib and who had at least one post-baseline PK sample available.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Experimental: Alectinib | Plasma Concentration of Alectinib Metabolite | 240 ng/mL | Geometric Coefficient of Variation 44.8 |
Secondary
Time to CNS Progression in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC
Time to CNS progression was defined as the time from randomization until radiographic evidence of CNS progression. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm and the appearance of new lesions. This outcome measure assessment was part of the primary analysis and was not repeated during final analysis.
Time frame: Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
Population: C-ITT included participants in ITT population with CNS metastasis at baseline (as per IRC assessment).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental: Alectinib | Time to CNS Progression in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC | NA months |
| Active Comparator: Premetrexed/Docetaxel | Time to CNS Progression in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC | 1.6 months |
Secondary
Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for C-ITT Population
TTD in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea \[single item and multi-item scales\] chest pain \[single item\], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-LC13.
Time frame: Baseline through study end (up to 33 months)
Population: C-ITT included participants in ITT population with CNS metastasis at baseline (as per IRC assessment). Number analyzed indicates number of participants evaluated for specified categories.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Experimental: Alectinib | Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for C-ITT Population | Coughing score | NA months |
| Experimental: Alectinib | Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for C-ITT Population | Dyspnoea score | 9.7 months |
| Experimental: Alectinib | Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for C-ITT Population | Pain in chest score | NA months |
| Experimental: Alectinib | Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for C-ITT Population | Pain in arm or shoulder score | 11.1 months |
| Active Comparator: Premetrexed/Docetaxel | Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for C-ITT Population | Pain in arm or shoulder score | 1.7 months |
| Active Comparator: Premetrexed/Docetaxel | Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for C-ITT Population | Coughing score | 16.6 months |
| Active Comparator: Premetrexed/Docetaxel | Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for C-ITT Population | Pain in chest score | NA months |
| Active Comparator: Premetrexed/Docetaxel | Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for C-ITT Population | Dyspnoea score | 1.4 months |
Secondary
Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for ITT Population
TTD in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea \[single item and multi-item scales\] chest pain \[single item\], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-LC13.
Time frame: Baseline through study end (up to 33 months)
Population: ITT population included all participants randomized in the study, irrespective of whether or not they received study drug. Number analyzed indicates number of participants evaluated for specified categories.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Experimental: Alectinib | Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for ITT Population | Coughing score | 18.1 months |
| Experimental: Alectinib | Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for ITT Population | Dyspnoea score | 4.1 months |
| Experimental: Alectinib | Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for ITT Population | Pain in chest score | NA months |
| Experimental: Alectinib | Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for ITT Population | Pain in arm or shoulder score | 12.5 months |
| Active Comparator: Premetrexed/Docetaxel | Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for ITT Population | Pain in arm or shoulder score | 1.9 months |
| Active Comparator: Premetrexed/Docetaxel | Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for ITT Population | Coughing score | 16.6 months |
| Active Comparator: Premetrexed/Docetaxel | Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for ITT Population | Pain in chest score | NA months |
| Active Comparator: Premetrexed/Docetaxel | Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for ITT Population | Dyspnoea score | 3.3 months |
Secondary
Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for C-ITT Population
TTD in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea \[single item and multi-item scales\] chest pain \[single item\], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-C30.
Time frame: Baseline through study end (up to 33 months)
Population: C-ITT included participants in ITT population with CNS metastasis at baseline (as per IRC assessment).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Experimental: Alectinib | Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for C-ITT Population | Dyspnoea score | 16.6 months |
| Experimental: Alectinib | Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for C-ITT Population | Fatigue score | 14.4 months |
| Active Comparator: Premetrexed/Docetaxel | Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for C-ITT Population | Dyspnoea score | 8.3 months |
| Active Comparator: Premetrexed/Docetaxel | Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for C-ITT Population | Fatigue score | 1.0 months |
Secondary
Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for ITT Population
TTD in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea \[single item and multi-item scales\] chest pain \[single item\], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-C30.
Time frame: Baseline through study end (up to 33 months)
Population: ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Experimental: Alectinib | Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for ITT Population | Dyspnoea score | 13.3 months |
| Experimental: Alectinib | Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for ITT Population | Fatigue score | 5.6 months |
| Active Comparator: Premetrexed/Docetaxel | Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for ITT Population | Dyspnoea score | 8.3 months |
| Active Comparator: Premetrexed/Docetaxel | Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for ITT Population | Fatigue score | 1.2 months |
Secondary
TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for C-ITT Population
TTD for a composite of three symptoms (cough, dyspnea, chest pain) in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for any component of the composite of the three following symptoms \[cough, dyspnea \[multi-item subscales QLQ-LC13\] and chest pain\]) as measured by the EORTC QLQ-LC13.
Time frame: Baseline through study end (up to 33 months)
Population: C-ITT included participants in ITT population with CNS metastasis at baseline (as per IRC assessment).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental: Alectinib | TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for C-ITT Population | 2.8 months |
| Active Comparator: Premetrexed/Docetaxel | TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for C-ITT Population | 1.4 months |
Secondary
TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for ITT Population
TTD for a composite of three symptoms (cough, dyspnea, chest pain) in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for any component of the composite of the three following symptoms \[cough, dyspnea \[multi-item subscales QLQ-LC13\] and chest pain\]) as measured by the EORTC QLQ-LC13.
Time frame: Baseline through study end (up to 33 months)
Population: ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental: Alectinib | TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for ITT Population | 1.4 months |
| Active Comparator: Premetrexed/Docetaxel | TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for ITT Population | 1.4 months |