Non-Small Cell Lung Cancer
Conditions
Brief summary
This randomized, active controlled, multicenter phase III open-label study is designed to evaluate the efficacy and safety of alectinib compared with crizotinib treatment in participants with treatment-naive anaplastic lymphoma kinase-positive (ALK-positive) advanced non-small cell lung cancer (NSCLC). Participants will be randomized in a 1:1 ratio to receive either alectinib, 600 milligrams (mg) orally twice daily (BID), or crizotinib, 250 mg orally BID. Participants will receive treatment until disease progression, unacceptable toxicity, withdrawal of consent, or death. The study is expected to last approximately 144 months.
Interventions
DRUGAlectinib
Participants will receive alectinib 600 mg orally (four 150 mg capsules) BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
DRUGCrizotinib
Participants will receive crizotinib 250 mg capsules orally BID from Visit 0 (baseline) 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 as assessed by the Ventana immunohistochemistry (IHC) test * Life expectancy of at least 12 weeks * Eastern cooperative oncology group performance status (ECOG PS) of 0-2 * Participants with no prior systemic treatment for advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC * Adequate renal, and hematologic function * Participants must have recovered from effects of any major surgery or significant traumatic injury at least 28 days before the first dose of study treatment * Measurable disease by response evaluation criteria in solid tumors (RECIST) version 1.1 (v1.1) prior to the administration of study treatment * Prior brain or leptomeningeal metastases allowed if asymptomatic (e.g., diagnosed incidentally at study baseline) * Negative pregnancy test for all females of child bearing potential * Use of highly effective contraception as defined by the study protocol
Exclusion criteria
* Participants with a previous malignancy within the past 3 years * Any gastrointestinal (GI) disorder or liver disease * National cancer institute common terminology criteria for adverse events (NCI CTCAE) (version 4.0) Grade 3 or higher toxicities due to any prior therapy (e.g., radiotherapy) (excluding alopecia) * History of organ transplant * Co-administration of anti-cancer therapies other than those administered in this study * Participants with baseline QTc greater than (\>) 470 milliseconds or symptomatic bradycardia * Recipient of strong/potent cytochrome P4503A inhibitors or inducers within 14 days prior to the first dose until the end of study treatment * Recipient of any drug with potential QT interval prolonging effects within 14 days prior to the first dose for all participants and while on treatment through the end of the study for crizotinib-treated participants only * History of hypersensitivity to any of the additives in the alectinib and crizotinib drug formulation * Pregnancy or lactation * Any clinically significant disease or condition (or history of) that could interfere with, or for which the treatment might interfere with, the conduct of the study or the absorption of oral medications or that would, in the opinion of the principal investigator, pose an unacceptable risk to the participant in this study * Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol requirements and/or follow-up procedures; those conditions should be discussed with the participant before trial entry
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) by Investigator Assessment | Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months) | PFS was assessed as time to disease progression or death whichever occurred first by investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) Criteria. 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. |
| Percentage of Participants With PFS Event by Investigator Assessment | Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months) | PFS was assessed percentage of participants with disease progression or death whichever occurred first by investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) Criteria. 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 Independent Review Committee (IRC)-Assessed | Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months) | PFS was assessed as time to disease progression or death whichever occurred first by IRC assessment using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) Criteria. 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. |
| Percentage of Participants With PFS Event by IRC | Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months) | PFS was assessed as percentage of participants with disease progression or death whichever occurred first by IRC assessment using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) Criteria. 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. |
| Percentage of Participants With Central Nervous System (CNS) Progression as Determined by IRC Using RECIST V1.1 Criteria | Randomization to CNS PD as first occurrence of disease progression (assessed every 8 weeks up to 33 months) | CNS progression was assessed as percentage of participants with an event defined as time from randomization until first radiographic evidence of CNS progression by IRC. The risk for a CNS progression without a prior non-CNS progression with alectinib compared with crizotinib. |
| Percentage of Participants With Central Nervous System (CNS) Progression as Determined by IRC Using Revised Assessment in Neuro Oncology (RANO) Criteria | Randomization to the first occurrence of disease progression in the CNS (assessed every 8 weeks up to 33 months) | CNS progression was assessed as percentage of participants with event defined as time from randomization until first radiographic evidence of CNS progression by IRC. The risk for a CNS progression without a prior non-CNS progression with alectinib compared with crizotinib. |
| Percentage of Participants With Objective Response Rate (ORR) of Complete Response (CR) or Partial Response (PR) as Determined by The Investigators According to RECIST V1.1 Criteria | Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks 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 (DOR) According to RECIST V1.1 Criteria as Assessed by the Investigators | First occurrence of objective response to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to approximately 10 years) | 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. |
| Overall Survival (OS) | From randomization until death (up to 10.5 years) | Overall survival (OS) was defined as the time from randomization to death from any cause. |
| Percentage of Participants With OS Event | From randomization until death (up to 10.5 years) | Overall survival (OS) was defined as the time from randomization to death from any cause. |
| Percentage of Participants With CNS ORR of CR or PR IRC-assessed According to RECIST v1.1 Criteria | Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months) | CNS ORR was defined as the percentage of participants who attained CR or PR and had measurable/non-measurable CNS lesions at baseline. 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. |
| CNS DOR IRC-assessed According to RECIST v1.1 Criteria | First occurrence of CNS objective response to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months) | CNS 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. |
| Percentage of Participants With Adverse Events | Baseline up to approximately 10 years | 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. |
| Area Under The Concentration-Time Curve (AUC) of Alectinib | Pre-dose (within 2 hours before alectinib) (baseline), 1, 2, 4, 6, and 8 hours post-dose at Visit 0 (first dosing day) and Week 4; Pre-dose (within 2 hours) at Week 8, then every 8 weeks until disease progression or death/withdrawal (up to 33 months) | — |
| Maximum Concentration (Cmax) of Alectinib | Pre-dose (within 2 hours before alectinib), 1, 2, 4, 6, and 8 hours post-dose at baseline and Week 4; Pre-dose (within 2 hours before alectinib) at Week 8, then every 8 weeks until disease progression or death/withdrawal from study (up to 33 months) | — |
| Time to Reach Cmax (Tmax) of Alectinib | Pre-dose (within 2 hours before alectinib), 1, 2, 4, 6, and 8 hours post-dose at baseline and Week 4; Pre-dose (within 2 hours before alectinib) at Week 8, then every 8 weeks until disease progression or death/withdrawal from study (up to 33 months) | — |
| AUC of Alectinib Metabolite | Pre-dose (within 2 hours before alectinib) (baseline), 1, 2, 4, 6, and 8 hours post-dose at Visit 0 (first dosing day) and Week 4; Pre-dose (within 2 hours) at Week 8, then every 8 weeks until disease progression or death/withdrawal (up to 33 months) | — |
| Cmax of Alectinib Metabolite | Pre-dose (within 2 hours before alectinib), 1, 2, 4, 6, and 8 hours post-dose at baseline and Week 4; Pre-dose (within 2 hours before alectinib) at Week 8, then every 8 weeks until disease progression or death/withdrawal from study (up to 33 months) | — |
| Tmax of Alectinib Metabolite | Pre-dose (within 2 hours before alectinib), 1, 2, 4, 6, and 8 hours post-dose at baseline and Week 4; Pre-dose (within 2 hours before alectinib) at Week 8, then every 8 weeks until disease progression or death/withdrawal from study (up to 33 months) | — |
| Time to Deterioration by European Organization for The Research And Treatment of Cancer (EORTC) Quality Of Life Questionnaire Core 30 (C30) | Baseline, every 4 weeks until disease progression (up to 33 months) | The EORTC QLQ-30 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. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning. Confirmed clinically meaningful deterioration in global health status or function is defined as a \>or=10-point decrease from baseline in a symptom score that must be held for at least two consecutive assessments or an initial \>or=10-point decrease from baseline followed by death within 5 weeks from the last assessment. |
| Percentage of Participants With Deterioration by EORTC Quality Of Life Questionnaire Core 30 (C30) | Baseline, every 4 weeks until disease progression (up to 33 months) | The EORTC QLQ-30 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. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning. Confirmed clinically meaningful deterioration in global health status or function is defined as a \>or=10-point decrease from baseline in a symptom score that must be held for at least two consecutive assessments or an initial \>or=10-point decrease from baseline followed by death within 5 weeks from the last assessment. |
| Time to Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13) | Baseline, every 4 weeks until disease progression (up to 33 months) | 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. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning. Confirmed clinically meaningful deterioration in lung cancer symptoms is defined as a \>or=10-point increase from baseline in a symptom score that must be held for at least two consecutive assessments or an initial \>or=10-point increase above baseline followed by death within 5 weeks from the last assessment. |
| Percentage of Participants With Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13) | Baseline, every 4 weeks until disease progression (up to 33 months) | 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. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning. Confirmed clinically meaningful deterioration in lung cancer symptoms is defined as a \>or=10-point increase from baseline in a symptom score that must be held for at least two consecutive assessments or an initial \>or=10-point increase above baseline followed by death within 5 weeks from the last assessment. |
| Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Baseline, every 4 weeks until disease progression (up to 33 months) | 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. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning. |
| HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Baseline, every 4 weeks until disease progression (up to 33 months) | 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. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning. |
| HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Baseline, every 4 weeks until disease progression (up to 33 months) | 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. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning. |
| HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Baseline, every 4 weeks until disease progression (up to 33 months) | 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. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning. |
| HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Baseline, every 4 weeks until disease progression (up to 33 months) | 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. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning. |
Countries
Australia, Bosnia and Herzegovina, Brazil, Canada, Chile, China, Costa Rica, Egypt, France, Guatemala, Hong Kong, Israel, Italy, Mexico, New Zealand, Poland, Portugal, Russia, Serbia, Singapore, South Korea, Spain, Switzerland, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Participant flow
Recruitment details
The study recruited treatment-naive participants with Anaplastic Lymphoma Kinase (ALK)-positive advanced Non-Small Cell Lung Cancer (NSCLC) in 29 countries from August 2014 to January 2016. The study achieved its protocol-defined definition of completion when the required number of death events was reached, at which point it could be terminated for all participants. The administrative study termination did not impact the overall study completion status.
Pre-assignment details
A total of 303 participants were randomized and included in the intent-to-treat (ITT) population; 152 participants in the alectinib arm and 151 participants in the crizotinib arm.
Participants by arm
| Arm | Count |
|---|---|
| Alectinib Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death. | 152 |
| Crizotinib Participants received crizotinib at 250 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death. | 151 |
| Total | 303 |
Baseline characteristics
| Characteristic | Crizotinib | Total | Alectinib |
|---|---|---|---|
| Age, Continuous | 53.8 years STANDARD_DEVIATION 13.5 | 55.1 years STANDARD_DEVIATION 12.8 | 56.3 years STANDARD_DEVIATION 12 |
| Race/Ethnicity, Customized Ethinicity - Not Hispanic or Latino | 136 Participants | 274 Participants | 138 Participants |
| Race/Ethnicity, Customized Ethnicity - Hispanic or Latino | 8 Participants | 16 Participants | 8 Participants |
| Race/Ethnicity, Customized Ethnicity - Not Stated | 7 Participants | 13 Participants | 6 Participants |
| Race/Ethnicity, Customized Race - American Indian or Alaska Native | 0 Participants | 4 Participants | 4 Participants |
| Race/Ethnicity, Customized Race - Asian | 69 Participants | 138 Participants | 69 Participants |
| Race/Ethnicity, Customized Race - Black or African American | 4 Participants | 4 Participants | 0 Participants |
| Race/Ethnicity, Customized Race - Native Hawaiian or other Pacific Islander | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Race - Unknown | 2 Participants | 4 Participants | 2 Participants |
| Race/Ethnicity, Customized Race - White | 75 Participants | 151 Participants | 76 Participants |
| Sex: Female, Male Female | 87 Participants | 171 Participants | 84 Participants |
| Sex: Female, Male Male | 64 Participants | 132 Participants | 68 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 76 / 152 | 73 / 151 |
| other Total, other adverse events | 138 / 152 | 143 / 151 |
| serious Total, serious adverse events | 70 / 152 | 48 / 151 |
Outcome results
Primary
Percentage of Participants With PFS Event by Investigator Assessment
PFS was assessed percentage of participants with disease progression or death whichever occurred first by investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) Criteria. 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 or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Population: ITT population included all randomized participants in the study. Number of participants analyzed is the total participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alectinib | Percentage of Participants With PFS Event by Investigator Assessment | 40.8 Percentage of Participants |
| Crizotinib | Percentage of Participants With PFS Event by Investigator Assessment | 67.5 Percentage of Participants |
Primary
Progression-Free Survival (PFS) by Investigator Assessment
PFS was assessed as time to disease progression or death whichever occurred first by investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) Criteria. 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 or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Population: ITT population included all randomized participants in the study. Number of participants analyzed is the total participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Alectinib | Progression-Free Survival (PFS) by Investigator Assessment | NA months |
| Crizotinib | Progression-Free Survival (PFS) by Investigator Assessment | 11.1 months |
Comparison: Stratified hazard ratio and p-value are stratified for covariates Race (Asian vs Non-Asian) and CNS metastases at baseline by IRC.p-value: <0.000195% CI: [0.34, 0.65]Log Rank
Secondary
Area Under The Concentration-Time Curve (AUC) of Alectinib
Time frame: Pre-dose (within 2 hours before alectinib) (baseline), 1, 2, 4, 6, and 8 hours post-dose at Visit 0 (first dosing day) and Week 4; Pre-dose (within 2 hours) at Week 8, then every 8 weeks until disease progression or death/withdrawal (up to 33 months)
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 | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Alectinib | Area Under The Concentration-Time Curve (AUC) of Alectinib | Treatment - week 4 | 5030 hr*ng/mL | Geometric Coefficient of Variation 47.2 |
| Alectinib | Area Under The Concentration-Time Curve (AUC) of Alectinib | Baseline | 713 hr*ng/mL | Geometric Coefficient of Variation 104.9 |
Secondary
AUC of Alectinib Metabolite
Time frame: Pre-dose (within 2 hours before alectinib) (baseline), 1, 2, 4, 6, and 8 hours post-dose at Visit 0 (first dosing day) and Week 4; Pre-dose (within 2 hours) at Week 8, then every 8 weeks until disease progression or death/withdrawal (up to 33 months)
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 | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Alectinib | AUC of Alectinib Metabolite | Baseline | 142 hr*ng/mL | Geometric Coefficient of Variation 191.7 |
| Alectinib | AUC of Alectinib Metabolite | Treatment - week 4 | 2230 hr*ng/mL | Geometric Coefficient of Variation 37 |
Secondary
Cmax of Alectinib Metabolite
Time frame: Pre-dose (within 2 hours before alectinib), 1, 2, 4, 6, and 8 hours post-dose at baseline and Week 4; Pre-dose (within 2 hours before alectinib) at Week 8, then every 8 weeks until disease progression or death/withdrawal from study (up to 33 months)
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 | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Alectinib | Cmax of Alectinib Metabolite | Baseline | 56.2 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 80.1 |
| Alectinib | Cmax of Alectinib Metabolite | Treatment - week 4 | 321 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 32 |
Secondary
CNS DOR IRC-assessed According to RECIST v1.1 Criteria
CNS 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.
Time frame: First occurrence of CNS objective response to first documented disease progression or death, whichever occurs first (assessed every 8 weeks 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 | Value (MEDIAN) |
|---|---|---|
| Alectinib | CNS DOR IRC-assessed According to RECIST v1.1 Criteria | 17.3 months |
| Crizotinib | CNS DOR IRC-assessed According to RECIST v1.1 Criteria | 5.5 months |
Secondary
Duration of Response (DOR) According to RECIST V1.1 Criteria as Assessed by the Investigators
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.
Time frame: First occurrence of objective response to first documented disease progression or death, whichever occurs first (assessed every 8 weeks 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 | Value (MEDIAN) |
|---|---|---|
| Alectinib | Duration of Response (DOR) According to RECIST V1.1 Criteria as Assessed by the Investigators | NA Months |
| Crizotinib | Duration of Response (DOR) According to RECIST V1.1 Criteria as Assessed by the Investigators | 11.1 Months |
Secondary
Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score
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. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning.
Time frame: Baseline, every 4 weeks until disease progression (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 time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Baseline | 66.67 Score on a scale |
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 4 | 66.67 Score on a scale |
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 8 | 75.0 Score on a scale |
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 12 | 75.0 Score on a scale |
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 16 | 75.0 Score on a scale |
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 20 | 75.0 Score on a scale |
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 24 | 75.0 Score on a scale |
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 28 | 75.0 Score on a scale |
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 32 | 75.0 Score on a scale |
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 36 | 79.17 Score on a scale |
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 40 | 75.0 Score on a scale |
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 44 | 83.33 Score on a scale |
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 48 | 66.67 Score on a scale |
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 52 | 83.33 Score on a scale |
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 56 | 75.0 Score on a scale |
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 60 | 75.0 Score on a scale |
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 64 | 75.0 Score on a scale |
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 68 | 75.0 Score on a scale |
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 72 | 75.0 Score on a scale |
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 76 | 75.0 Score on a scale |
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 80 | 75.0 Score on a scale |
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 84 | 83.33 Score on a scale |
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 88 | 75.0 Score on a scale |
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 92 | 70.83 Score on a scale |
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 96 | 66.67 Score on a scale |
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 100 | 66.67 Score on a scale |
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 104 | 66.67 Score on a scale |
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 108 | 66.67 Score on a scale |
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 112 | 75.0 Score on a scale |
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 116 | 70.83 Score on a scale |
| Alectinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 120 | 83.3 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 60 | 75.0 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Baseline | 66.67 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 92 | 75.0 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 4 | 66.67 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 64 | 83.33 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 8 | 75.0 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 108 | 75.0 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 12 | 75.0 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 68 | 79.17 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 16 | 83.33 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 96 | 66.67 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 20 | 75.0 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 72 | 75.00 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 24 | 83.33 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 116 | 91.67 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 28 | 75.0 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 76 | 75.0 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 32 | 66.67 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 100 | 75.0 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 36 | 66.67 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 80 | 75.0 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 40 | 83.33 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 112 | 75.0 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 44 | 83.33 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 84 | 66.67 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 48 | 83.33 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 104 | 66.67 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 52 | 75.00 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 88 | 66.67 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 56 | 75.0 Score on a scale |
| Crizotinib | Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score | Treatment - week 120 | NA Score on a scale |
Secondary
HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing
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. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning.
Time frame: Baseline, every 4 weeks until disease progression (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 time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Baseline | 33.33 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 4 | 33.33 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 8 | 33.33 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 12 | 33.33 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 16 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 20 | 33.33 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 24 | 33.33 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 28 | 33.33 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 32 | 33.33 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 36 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 40 | 33.33 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 44 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 48 | 33.33 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 52 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 56 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 60 | 33.33 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 64 | 33.33 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 68 | 33.33 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 72 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 76 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 80 | 33.33 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 84 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 88 | 33.33 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 92 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 96 | 16.67 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 100 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 104 | 33.33 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 108 | 33.33 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 112 | 33.33 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 116 | 33.33 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 120 | 33.33 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Baseline | 33.33 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 60 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 4 | 33.33 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 104 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 8 | 33.33 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 64 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 12 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 92 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 16 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 68 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 20 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 112 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 24 | 33.33 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 72 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 28 | 16.67 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 96 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 32 | 33.33 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 76 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 36 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 108 | 33.33 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 40 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 80 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 44 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 100 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 48 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 84 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 52 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 116 | 16.67 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 56 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing | Treatment - week 88 | 0.0 Score on a scale |
Secondary
HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea
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. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning.
Time frame: Baseline, every 4 weeks until disease progression (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 time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 28 | 11.11 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Baseline | 22.22 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 4 | 22.22 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 8 | 22.22 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 12 | 22.22 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 16 | 22.22 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 20 | 22.22 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 24 | 22.22 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 32 | 22.22 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 36 | 16.67 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 40 | 11.11 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 44 | 11.11 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 48 | 22.22 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 52 | 22.22 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 56 | 22.22 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 60 | 22.22 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 64 | 22.22 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 68 | 22.22 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 72 | 22.22 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 76 | 11.11 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 80 | 22.22 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 84 | 11.11 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 88 | 22.22 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 92 | 22.22 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 96 | 22.22 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 100 | 22.22 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 104 | 11.11 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 108 | 22.22 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 112 | 11.11 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 116 | 16.67 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 120 | 22.22 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 60 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Baseline | 22.22 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 104 | 11.11 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 4 | 22.22 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 64 | 11.11 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 8 | 11.11 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 92 | 22.22 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 12 | 11.11 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 68 | 11.11 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 16 | 11.11 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 112 | 27.78 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 72 | 11.11 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 24 | 11.11 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 20 | 11.11 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 28 | 11.11 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 96 | 22.22 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 32 | 11.11 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 76 | 11.11 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 36 | 11.11 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 108 | 11.11 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 40 | 5.56 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 80 | 11.11 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 44 | 11.11 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 100 | 27.78 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 48 | 11.11 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 84 | 11.11 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 52 | 11.11 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 116 | 16.67 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 56 | 11.11 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea | Treatment - Week 88 | 22.22 Score on a scale |
Secondary
HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder
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. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning.
Time frame: Baseline, every 4 weeks until disease progression (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 time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 60 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 32 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 64 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 12 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 68 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 36 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 72 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 4 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 76 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 40 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 80 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 20 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 84 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 88 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 44 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 92 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Baseline | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 96 | 33.33 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 48 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 100 | 33.33 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 24 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 104 | 33.33 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 52 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 108 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 8 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 112 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 56 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 116 | 16.67 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 28 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 120 | 33.33 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 16 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 84 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Baseline | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 4 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 8 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 16 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 20 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 24 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 28 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 32 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 36 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 40 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 44 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 48 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 52 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 56 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 12 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 60 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 64 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 68 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 72 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 76 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 80 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 88 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 92 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 96 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 100 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 104 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 108 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 112 | 16.67 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder | Treatment - Week 116 | 16.67 Score on a scale |
Secondary
HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest
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. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning.
Time frame: Baseline, every 4 weeks until disease progression (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 time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 88 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 96 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Baseline | 33.33 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 4 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 8 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 12 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 16 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 20 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 24 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 28 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 32 | 0.00 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 36 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 40 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 44 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 48 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 52 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 56 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 60 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 64 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 68 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 72 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 76 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 84 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 80 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 92 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 100 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 104 | 33.33 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 108 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 112 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 116 | 0.0 Score on a scale |
| Alectinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 120 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 92 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 104 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Baseline | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 56 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 88 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 4 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 60 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 8 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 112 | 16.67 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 12 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 64 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 16 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 96 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 20 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 68 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 24 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 108 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 28 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 72 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 32 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 100 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 36 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 76 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 40 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 80 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 44 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 116 | 16.67 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 48 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 84 | 0.0 Score on a scale |
| Crizotinib | HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest | Treatment - Week 52 | 0.0 Score on a scale |
Secondary
Maximum Concentration (Cmax) of Alectinib
Time frame: Pre-dose (within 2 hours before alectinib), 1, 2, 4, 6, and 8 hours post-dose at baseline and Week 4; Pre-dose (within 2 hours before alectinib) at Week 8, then every 8 weeks until disease progression or death/withdrawal from study (up to 33 months)
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 | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Alectinib | Maximum Concentration (Cmax) of Alectinib | Baseline | 211 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 55.5 |
| Alectinib | Maximum Concentration (Cmax) of Alectinib | Treatment - week 4 | 717 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 46.8 |
Secondary
Overall Survival (OS)
Overall survival (OS) was defined as the time from randomization to death from any cause.
Time frame: From randomization until death (up to 43 months)
Population: ITT population included all randomized participants in the study. Number of participants analyzed is the total participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Alectinib | Overall Survival (OS) | NA months |
| Crizotinib | Overall Survival (OS) | NA months |
p-value: 0.240595% CI: [0.48, 1.2]Log Rank
Secondary
Percentage of Participants With Adverse Events
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 up to 28 months in the crizotinib arm and up to 30 months in the alectinib arm
Population: Safety (SAF) population included all participants who received at least one dose of any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alectinib | Percentage of Participants With Adverse Events | 97.0 Percentage of Participants |
| Crizotinib | Percentage of Participants With Adverse Events | 97.0 Percentage of Participants |
Secondary
Percentage of Participants With Central Nervous System (CNS) Progression as Determined by IRC Using RECIST V1.1 Criteria
CNS progression was assessed as percentage of participants with an event defined as time from randomization until first radiographic evidence of CNS progression by IRC. The risk for a CNS progression without a prior non-CNS progression with alectinib compared with crizotinib.
Time frame: Randomization to CNS PD as first occurrence of disease progression (assessed every 8 weeks up to 33 months)
Population: ITT population included all randomized participants in the study. Number of participants analyzed is the total participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alectinib | Percentage of Participants With Central Nervous System (CNS) Progression as Determined by IRC Using RECIST V1.1 Criteria | 11.8 Percentage of Participants |
| Crizotinib | Percentage of Participants With Central Nervous System (CNS) Progression as Determined by IRC Using RECIST V1.1 Criteria | 45.0 Percentage of Participants |
p-value: <0.000195% CI: [0.1, 0.28]Log Rank
Secondary
Percentage of Participants With Central Nervous System (CNS) Progression as Determined by IRC Using Revised Assessment in Neuro Oncology (RANO) Criteria
CNS progression was assessed as percentage of participants with event defined as time from randomization until first radiographic evidence of CNS progression by IRC. The risk for a CNS progression without a prior non-CNS progression with alectinib compared with crizotinib.
Time frame: Randomization to the first occurrence of disease progression in the CNS (assessed every 8 weeks up to 33 months)
Population: ITT population included all randomized participants in the study. Number of participants analyzed is the total participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alectinib | Percentage of Participants With Central Nervous System (CNS) Progression as Determined by IRC Using Revised Assessment in Neuro Oncology (RANO) Criteria | 10.5 Percentage of Participants |
| Crizotinib | Percentage of Participants With Central Nervous System (CNS) Progression as Determined by IRC Using Revised Assessment in Neuro Oncology (RANO) Criteria | 35.8 Percentage of Participants |
Secondary
Percentage of Participants With CNS ORR of CR or PR IRC-assessed According to RECIST v1.1 Criteria
CNS ORR was defined as the percentage of participants who attained CR or PR and had measurable/non-measurable CNS lesions at baseline. 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: Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Population: ITT population included all randomized participants in the study. Number of participants analyzed is the total participants who were evaluable for this outcome measure (number of participants with measurable/non-measurable CNS lesions at baseline).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alectinib | Percentage of Participants With CNS ORR of CR or PR IRC-assessed According to RECIST v1.1 Criteria | Measurable CNS lesions at baseline | 81.0 Percentage of Participants |
| Alectinib | Percentage of Participants With CNS ORR of CR or PR IRC-assessed According to RECIST v1.1 Criteria | Measurable and non-measurable CNS lesions | 59.4 Percentage of Participants |
| Crizotinib | Percentage of Participants With CNS ORR of CR or PR IRC-assessed According to RECIST v1.1 Criteria | Measurable CNS lesions at baseline | 50.0 Percentage of Participants |
| Crizotinib | Percentage of Participants With CNS ORR of CR or PR IRC-assessed According to RECIST v1.1 Criteria | Measurable and non-measurable CNS lesions | 25.9 Percentage of Participants |
Secondary
Percentage of Participants With Deterioration by EORTC Quality Of Life Questionnaire Core 30 (C30)
The EORTC QLQ-30 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. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning. Confirmed clinically meaningful deterioration in global health status or function is defined as a \>or=10-point decrease from baseline in a symptom score that must be held for at least two consecutive assessments or an initial \>or=10-point decrease from baseline followed by death within 5 weeks from the last assessment.
Time frame: Baseline, every 4 weeks until disease progression (up to 33 months)
Population: ITT population included all randomized participants in the study. Number of participants analyzed is the total participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alectinib | Percentage of Participants With Deterioration by EORTC Quality Of Life Questionnaire Core 30 (C30) | Fatigue | 21.7 Percentage of Participants |
| Alectinib | Percentage of Participants With Deterioration by EORTC Quality Of Life Questionnaire Core 30 (C30) | Dyspnea | 17.1 Percentage of Participants |
| Crizotinib | Percentage of Participants With Deterioration by EORTC Quality Of Life Questionnaire Core 30 (C30) | Fatigue | 25.2 Percentage of Participants |
| Crizotinib | Percentage of Participants With Deterioration by EORTC Quality Of Life Questionnaire Core 30 (C30) | Dyspnea | 9.9 Percentage of Participants |
Secondary
Percentage of Participants With Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13)
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. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning. Confirmed clinically meaningful deterioration in lung cancer symptoms is defined as a \>or=10-point increase from baseline in a symptom score that must be held for at least two consecutive assessments or an initial \>or=10-point increase above baseline followed by death within 5 weeks from the last assessment.
Time frame: Baseline, every 4 weeks until disease progression (up to 33 months)
Population: ITT population included all randomized participants in the study. Number of participants analyzed is the total participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alectinib | Percentage of Participants With Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13) | Dyspnea | 28 Percentage of Participants |
| Alectinib | Percentage of Participants With Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13) | Pain in chest | 7 Percentage of Participants |
| Alectinib | Percentage of Participants With Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13) | Pain in arm and shoulder | 18 Percentage of Participants |
| Alectinib | Percentage of Participants With Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13) | Composite score (c, p in c, d) | 32 Percentage of Participants |
| Alectinib | Percentage of Participants With Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13) | Coughing | 11 Percentage of Participants |
| Crizotinib | Percentage of Participants With Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13) | Composite score (c, p in c, d) | 28 Percentage of Participants |
| Crizotinib | Percentage of Participants With Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13) | Coughing | 11 Percentage of Participants |
| Crizotinib | Percentage of Participants With Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13) | Dyspnea | 16 Percentage of Participants |
| Crizotinib | Percentage of Participants With Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13) | Pain in arm and shoulder | 12 Percentage of Participants |
| Crizotinib | Percentage of Participants With Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13) | Pain in chest | 11 Percentage of Participants |
Secondary
Percentage of Participants With Objective Response Rate (ORR) of Complete Response (CR) or Partial Response (PR) as Determined by The Investigators According to RECIST V1.1 Criteria
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: Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Population: ITT population included all randomized participants in the study. Number of participants analyzed is the total participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alectinib | Percentage of Participants With Objective Response Rate (ORR) of Complete Response (CR) or Partial Response (PR) as Determined by The Investigators According to RECIST V1.1 Criteria | 82.9 Percentage of Participants |
| Crizotinib | Percentage of Participants With Objective Response Rate (ORR) of Complete Response (CR) or Partial Response (PR) as Determined by The Investigators According to RECIST V1.1 Criteria | 75.5 Percentage of Participants |
p-value: 0.093695% CI: [-1.71, 16.5]Mantel Haenszel
Secondary
Percentage of Participants With OS Event
Overall survival (OS) was defined as the time from randomization to death from any cause.
Time frame: From randomization until death (up to 43 months)
Population: ITT population included all randomized participants in the study. Number of participants analyzed is the total participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alectinib | Percentage of Participants With OS Event | 23.0 Percentage of Participants |
| Crizotinib | Percentage of Participants With OS Event | 26.5 Percentage of Participants |
Secondary
Percentage of Participants With PFS Event by IRC
PFS was assessed as percentage of participants with disease progression or death whichever occurred first by IRC assessment using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) Criteria. 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.
Time frame: Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Population: ITT population included all randomized participants in the study. Number of participants analyzed is the total participants who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alectinib | Percentage of Participants With PFS Event by IRC | 41.4 Percentage of Participants |
| Crizotinib | Percentage of Participants With PFS Event by IRC | 60.9 Percentage of Participants |
Secondary
PFS Independent Review Committee (IRC)-Assessed
PFS was assessed as time to disease progression or death whichever occurred first by IRC assessment using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) Criteria. 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.
Time frame: Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Population: ITT population included all randomized participants in the study. Number of participants analyzed is the total participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Alectinib | PFS Independent Review Committee (IRC)-Assessed | 25.7 months |
| Crizotinib | PFS Independent Review Committee (IRC)-Assessed | 10.4 months |
p-value: <0.000195% CI: [0.36, 0.7]Log Rank
Secondary
Time to Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13)
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. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning. Confirmed clinically meaningful deterioration in lung cancer symptoms is defined as a \>or=10-point increase from baseline in a symptom score that must be held for at least two consecutive assessments or an initial \>or=10-point increase above baseline followed by death within 5 weeks from the last assessment.
Time frame: Baseline, every 4 weeks until disease progression (up to 33 months)
Population: ITT population included all randomized participants in the study. Number of participants analyzed is the total participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Alectinib | Time to Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13) | Dyspnea | 22.8 months |
| Alectinib | Time to Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13) | Pain in chest | NA months |
| Alectinib | Time to Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13) | Pain in arm and shoulder | NA months |
| Alectinib | Time to Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13) | Composite score (c, p in c, d) | 12.7 months |
| Alectinib | Time to Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13) | Coughing | NA months |
| Crizotinib | Time to Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13) | Composite score (c, p in c, d) | 21.0 months |
| Crizotinib | Time to Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13) | Coughing | NA months |
| Crizotinib | Time to Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13) | Dyspnea | NA months |
| Crizotinib | Time to Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13) | Pain in arm and shoulder | NA months |
| Crizotinib | Time to Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13) | Pain in chest | NA months |
Comparison: Coughingp-value: 0.704295% CI: [0.44, 1.74]Log Rank
Comparison: Dyspneap-value: 0.028595% CI: [1.05, 2.92]Log Rank
Comparison: Pain in arm and shoulderp-value: 0.237795% CI: [0.79, 2.61]Log Rank
Comparison: Pain in chestp-value: 0.079695% CI: [0.24, 1.1]Log Rank
Comparison: Composite scorep-value: 0.643595% CI: [0.72, 1.68]Log Rank
Secondary
Time to Deterioration by European Organization for The Research And Treatment of Cancer (EORTC) Quality Of Life Questionnaire Core 30 (C30)
The EORTC QLQ-30 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. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning. Confirmed clinically meaningful deterioration in global health status or function is defined as a \>or=10-point decrease from baseline in a symptom score that must be held for at least two consecutive assessments or an initial \>or=10-point decrease from baseline followed by death within 5 weeks from the last assessment.
Time frame: Baseline, every 4 weeks until disease progression (up to 33 months)
Population: ITT population included all randomized participants in the study. Number of participants analyzed is the total participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Alectinib | Time to Deterioration by European Organization for The Research And Treatment of Cancer (EORTC) Quality Of Life Questionnaire Core 30 (C30) | Fatigue | NA months |
| Alectinib | Time to Deterioration by European Organization for The Research And Treatment of Cancer (EORTC) Quality Of Life Questionnaire Core 30 (C30) | Dyspnea | NA months |
| Crizotinib | Time to Deterioration by European Organization for The Research And Treatment of Cancer (EORTC) Quality Of Life Questionnaire Core 30 (C30) | Fatigue | NA months |
| Crizotinib | Time to Deterioration by European Organization for The Research And Treatment of Cancer (EORTC) Quality Of Life Questionnaire Core 30 (C30) | Dyspnea | NA months |
Comparison: Fatiguep-value: 0.207995% CI: [0.46, 1.19]Log Rank
Comparison: Dyspneap-value: 0.113795% CI: [0.88, 3.15]Log Rank
Secondary
Time to Reach Cmax (Tmax) of Alectinib
Time frame: Pre-dose (within 2 hours before alectinib), 1, 2, 4, 6, and 8 hours post-dose at baseline and Week 4; Pre-dose (within 2 hours before alectinib) at Week 8, then every 8 weeks until disease progression or death/withdrawal from study (up to 33 months)
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 | Group | Value (MEDIAN) |
|---|---|---|---|
| Alectinib | Time to Reach Cmax (Tmax) of Alectinib | Baseline | 6.03 hours |
| Alectinib | Time to Reach Cmax (Tmax) of Alectinib | Treatment - week 4 | 4.02 hours |
Secondary
Tmax of Alectinib Metabolite
Time frame: Pre-dose (within 2 hours before alectinib), 1, 2, 4, 6, and 8 hours post-dose at baseline and Week 4; Pre-dose (within 2 hours before alectinib) at Week 8, then every 8 weeks until disease progression or death/withdrawal from study (up to 33 months)
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 | Group | Value (MEDIAN) |
|---|---|---|---|
| Alectinib | Tmax of Alectinib Metabolite | Baseline | 8.00 hours |
| Alectinib | Tmax of Alectinib Metabolite | Treatment - week 4 | 6.00 hours |