A Study Comparing Alectinib With Crizotinib in Treatment-Naive Anaplastic Lymphoma Kinase-Positive Advanced Non-Small Cell Lung Cancer Participants

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

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)