Trial Outcomes & Findings for Alectinib Versus Pemetrexed or Docetaxel in Anaplastic Lymphoma Kinase (ALK)-Positive Advanced Non-Small Cell Lung Cancer (NSCLC) Participants Previously Treated With Platinum-Based Chemotherapy and Crizotinib (NCT NCT02604342)

Last Updated: 2019-10-29

Results Overview

PFS was defined as the time from randomization to the first documented disease progression, as determined using RECIST v1.1, or death from any cause, whichever occurred first. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 millimeter (mm) and the appearance of new lesions.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

119 participants

Primary outcome timeframe

Randomization to first documented disease progression, death from any cause, or study end (up to 33 months)

Results posted on

2019-10-29

Participant Flow

The study recruited participants with Anaplastic Lymphoma Kinase (ALK)-positive advanced Non-Small Cell Lung Cancer (NSCLC) in 13 countries from November 2015 to March 2017.

A total of 119 participants were enrolled and randomized into the study: 79 participants in the alectinib arm, and 40 participants in the chemotherapy arm.

Participant milestones

Participant milestones
Measure	Experimental: Alectinib Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Active Comparator: Premetrexed/Docetaxel Participants received chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously.
Overall Study STARTED	79	40
Overall Study COMPLETED	36	17
Overall Study NOT COMPLETED	43	23

Reasons for withdrawal

Reasons for withdrawal
Measure	Experimental: Alectinib Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Active Comparator: Premetrexed/Docetaxel Participants received chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously.
Overall Study Death	32	16
Overall Study Progression of disease	1	0
Overall Study Withdrawal by Subject	5	6
Overall Study Other	1	0
Overall Study Study Termination by Sponsor	1	0
Overall Study Lost to Follow-up	1	1
Overall Study Physician Decision	2	0

Baseline Characteristics

Alectinib Versus Pemetrexed or Docetaxel in Anaplastic Lymphoma Kinase (ALK)-Positive Advanced Non-Small Cell Lung Cancer (NSCLC) Participants Previously Treated With Platinum-Based Chemotherapy and Crizotinib

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Experimental: Alectinib n=79 Participants Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Active Comparator: Premetrexed/Docetaxel n=40 Participants Participants received chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously.	Total n=119 Participants Total of all reporting groups
Age, Continuous	54.6 years STANDARD_DEVIATION 13.0 • n=5 Participants	58.8 years STANDARD_DEVIATION 10.5 • n=7 Participants	56.0 years STANDARD_DEVIATION 12.4 • n=5 Participants
Sex: Female, Male Female	33 Participants n=5 Participants	20 Participants n=7 Participants	53 Participants n=5 Participants
Sex: Female, Male Male	46 Participants n=5 Participants	20 Participants n=7 Participants	66 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	68 Participants n=5 Participants	34 Participants n=7 Participants	102 Participants n=5 Participants
Race/Ethnicity, Customized Not reported	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	5 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Missing	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White	67 Participants n=5 Participants	32 Participants n=7 Participants	99 Participants n=5 Participants
Race/Ethnicity, Customized Asian	6 Participants n=5 Participants	8 Participants n=7 Participants	14 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Randomization to first documented disease progression, death from any cause, or study end (up to 33 months)

Population: ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.

Outcome measures

Outcome measures
Measure	Experimental: Alectinib n=79 Participants Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Active Comparator: Premetrexed/Docetaxel n=40 Participants Participants received chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously.
Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator	10.9 months Interval 8.1 to 15.5	1.4 months Interval 1.2 to 1.6

SECONDARY outcome

Timeframe: Baseline through study end (up to 33 months)

Population: ITT population with measurable CNS metastasis (mc-ITT) included all participants in ITT population with measurable CNS metastasis at baseline (as per IRC).

Overall response rate in subjects with confirmed CNS response (C-ORR) was defined as the percentage of subjects who attained Complete Response (CR) or Partial Response (PR) for lesions in the CNS. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.

Outcome measures

Outcome measures
Measure	Experimental: Alectinib n=24 Participants Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Active Comparator: Premetrexed/Docetaxel n=17 Participants Participants received chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously.
Percentage of Participants With CNS Objective Response Rate (ORR) With Measurable CNS Metastases at Baseline Using RECIST Version 1.1 as Assessed By IRC	66.7 percentage of participants	0.0 percentage of participants

SECONDARY outcome

Timeframe: Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)

Population: ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.

Outcome measures

Outcome measures
Measure	Experimental: Alectinib n=72 Participants Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Active Comparator: Premetrexed/Docetaxel n=35 Participants Participants received chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously.
PFS Using RECIST Version 1.1 as Assessed by IRC	7.1 months Interval 6.3 to 10.8	1.6 months Interval 1.3 to 4.1

SECONDARY outcome

Timeframe: Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)

Population: ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.

ORR was defined as the percentage of participants who attained CR or PR. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. The IRC assessment was part of the primary analysis and was not repeated during final analysis.

Outcome measures

Outcome measures
Measure	Experimental: Alectinib n=79 Participants Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Active Comparator: Premetrexed/Docetaxel n=40 Participants Participants received chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously.
Percentage of Participants With Objective Response of CR or PR Using RECIST Version 1.1 as Assessed by Investigator and IRC Assessed by Investigator	50.6 percentage of participants	2.5 percentage of participants
Percentage of Participants With Objective Response of CR or PR Using RECIST Version 1.1 as Assessed by Investigator and IRC Assessed by IRC	36.1 percentage of participants	11.4 percentage of participants

SECONDARY outcome

Timeframe: Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)

Population: ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.

Disease control rate (DCR) was defined as the percentage of participants who attained CR, PR, or stable disease (SD) of at least 5 weeks. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters, SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters since the treatment started. The IRC assessment was part of the primary analysis and was not repeated during final analysis.

Outcome measures

Outcome measures
Measure	Experimental: Alectinib n=79 Participants Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Active Comparator: Premetrexed/Docetaxel n=40 Participants Participants received chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously.
Percentage of Participants With Disease Control Using RECIST Version 1.1 as Assessed by Investigator and IRC Assessed by Investigator	86.1 percentage of participants	25.0 percentage of participants
Percentage of Participants With Disease Control Using RECIST Version 1.1 as Assessed by Investigator and IRC Assessed by IRC	76.4 percentage of participants	48.6 percentage of participants

SECONDARY outcome

Timeframe: From the first documented CR or PR to the first documented disease progression, death, or study end (up to 33 months)

Population: ITT population included all participants randomized in the study, irrespective of whether or not they received study drug. Number analyzed indicates number of participants with a BOR of CR or PR.

DOR was defined as the time from when response (CR or PR) was first documented to first documented disease progression or death, whichever occurred first. DOR was evaluated for participants who had a best overall response (BOR) of CR or PR. The IRC assessment was part of the primary analysis and was not repeated during final analysis.

Outcome measures

Outcome measures
Measure	Experimental: Alectinib n=79 Participants Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Active Comparator: Premetrexed/Docetaxel n=40 Participants Participants received chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously.
Duration of Response (DOR) Using RECIST Version 1.1 as Assessed by Investigator and IRC Assessed by Investigator	12.0 months Interval 8.3 to 23.5	2.7 months CI could not be calculated due to insufficient number of participants with the event
Duration of Response (DOR) Using RECIST Version 1.1 as Assessed by Investigator and IRC Assessed by IRC	9.7 months Interval 5.6 to The upper CI limit could not be calculated due to an insufficient number of participants with the event	NA months Values could not be calculated due to an insufficient number of participants with the event

SECONDARY outcome

Timeframe: Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)

Population: Intent-to-treat population with CNS metastasis (C-ITT) included participants in ITT population with CNS metastasis at baseline (as per IRC assessment).

Outcome measures

Outcome measures
Measure	Experimental: Alectinib n=50 Participants Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Active Comparator: Premetrexed/Docetaxel n=26 Participants Participants received chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously.
PFS in C-ITT Population Using RECIST Version 1.1 as Assessed by Investigator and IRC Assessed by Investigator	9.7 months Interval 6.9 to The upper limit of CI was not reached due to less number of participants with the event.	1.4 months Interval 1.2 to 1.6
PFS in C-ITT Population Using RECIST Version 1.1 as Assessed by Investigator and IRC Assessed by IRC	8.1 months Interval 6.3 to The upper limit of CI was not reached due to less number of participants with the event.	1.5 months Interval 1.2 to 4.1

SECONDARY outcome

Timeframe: Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)

Population: C-ITT included participants in ITT population with CNS metastasis at baseline (as per IRC assessment).

Time to CNS progression was defined as the time from randomization until radiographic evidence of CNS progression. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm and the appearance of new lesions. This outcome measure assessment was part of the primary analysis and was not repeated during final analysis.

Outcome measures

Outcome measures
Measure	Experimental: Alectinib n=50 Participants Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Active Comparator: Premetrexed/Docetaxel n=26 Participants Participants received chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously.
Time to CNS Progression in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC	NA months Interval 6.8 to The median and upper limit of CI was not reached due to less number of participants with the event.	1.6 months Interval 1.3 to 9.9

SECONDARY outcome

Timeframe: From first documented CR, PR, or SD lasting at least 5 weeks through study end (up to 33 months)

Population: C-ITT included participants in ITT population with CNS metastasis at baseline (as per IRC assessment).

Disease Control Rate (DCR) was defined as the percentage of participants who attained CR, PR, or stable disease (SD) of at least 5 weeks. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters, SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters since the treatment started.

Outcome measures

Outcome measures
Measure	Experimental: Alectinib n=52 Participants Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Active Comparator: Premetrexed/Docetaxel n=28 Participants Participants received chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously.
Percentage of Participants With Disease Control in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC	82.7 percentage of participants	25.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline through study end (up to 33 months)

Population: C-ITT included participants in ITT population with CNS metastasis at baseline (as per IRC assessment).

Outcome measures

Outcome measures
Measure	Experimental: Alectinib n=52 Participants Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Active Comparator: Premetrexed/Docetaxel n=28 Participants Participants received chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously.
Percentage of Participants With ORR in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC	48.1 percentage of participants	0.0 percentage of participants

SECONDARY outcome

Timeframe: From the first documented CR or PR to the first documented disease progression, death, or study end (up to 33 months)

Population: C-ITT included participants in ITT population with CNS metastasis at baseline (as per IRC assessment). Number analyzed indicates number of participants with a BOR of CR or PR.

DOR was defined as the time from when response (CR or PR) was first documented to first documented disease progression or death, whichever occurred first. C-DOR was defined in a similar way for lesions in the CNS, taking into account all lesions in the body. DOR was evaluated for participants who had a BOR of CR or PR.

Outcome measures

Outcome measures
Measure	Experimental: Alectinib n=52 Participants Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Active Comparator: Premetrexed/Docetaxel n=28 Participants Participants received chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously.
Duration of Response for Lesions in the CNS (C-DOR) Using RECIST Version 1.1 as Assessed by IRC	13.9 months Interval 6.2 to 13.9	NA months Could not be calculated due to insufficient number of participants with the event

SECONDARY outcome

Timeframe: Randomization to death from any cause, through study end (up to 33 months)

Population: ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.

Overall survival (OS) was defined as the time from randomization to death from any cause. OS was confounded by cross-over of participants to the alectinib arm.

Outcome measures

Outcome measures
Measure	Experimental: Alectinib n=79 Participants Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Active Comparator: Premetrexed/Docetaxel n=40 Participants Participants received chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously.
Overall Survival (OS)	27.8 months Interval 18.2 to The upper limit of CI was not reached due to less number of participants with the event.	NA months Interval 8.6 to The median and CI was not reached due to less number of participants with the event.

SECONDARY outcome

Timeframe: Predose (2 hours) at Baseline, Week 3 and Week 6

Population: The Pharmacokinetic (PK) Evaluable Population included all participants who received any dose of alectinib and who had at least one post-baseline PK sample available.

Outcome measures

Outcome measures
Measure	Experimental: Alectinib n=56 Participants Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Active Comparator: Premetrexed/Docetaxel Participants received chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously.
Plasma Concentration of Alectinib	559 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 48.0	—

SECONDARY outcome

Timeframe: Predose (2 hours) at Baseline, Week 3 and Week 6

Population: The PK Evaluable Population included all participants who received any dose of alectinib and who had at least one post-baseline PK sample available.

Outcome measures

Outcome measures
Measure	Experimental: Alectinib n=56 Participants Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Active Comparator: Premetrexed/Docetaxel Participants received chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously.
Plasma Concentration of Alectinib Metabolite	240 ng/mL Geometric Coefficient of Variation 44.8	—

SECONDARY outcome

Timeframe: Baseline through Week 138

Population: ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.

Percentage of participants who filled out an EORTC QLQ-C30 questionnaire at a visit. The EORTC QLQ-C30 questionnaire consisted of 30 questions generating five functional scores (physical, role, cognitive, emotional, and social); a global health status/global quality of life scale score; three symptom scale scores (fatigue, pain, and nausea and vomiting); and six stand alone one-item scores that capture additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and perceived financial burden.

Outcome measures

Outcome measures
Measure	Experimental: Alectinib n=79 Participants Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Active Comparator: Premetrexed/Docetaxel n=40 Participants Participants received chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously.
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time Baseline	92.4 percentage of participants	85.0 percentage of participants
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time Treatment - Week 3	96.1 percentage of participants	83.3 percentage of participants
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time Treatment - Week 6	97.2 percentage of participants	60.0 percentage of participants
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time Treatment - Week 12	95.5 percentage of participants	80.0 percentage of participants
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time Treatment - Week 18	88.5 percentage of participants	50.0 percentage of participants
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time Treatment - Week 24	91.1 percentage of participants	100 percentage of participants
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time Treatment - Week 30	96.2 percentage of participants	66.7 percentage of participants
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time Treatment - Week 36	89.8 percentage of participants	66.7 percentage of participants
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time Treatment - Week 42	95.3 percentage of participants	66.7 percentage of participants
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time Treatment - Week 48	100 percentage of participants	100 percentage of participants
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time Treatment - Week 54	97.1 percentage of participants	100 percentage of participants
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time Treatment - Week 60	100 percentage of participants	100 percentage of participants
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time Treatment - Week 66	89.7 percentage of participants	100 percentage of participants
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time Treatment - Week 72	88.9 percentage of participants	100 percentage of participants
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time Treatment - Week 78	84.6 percentage of participants	—
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time Treatment - Week 84	78.3 percentage of participants	—
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time Treatment - Week 90	88.9 percentage of participants	—
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time Treatment - Week 96	93.8 percentage of participants	—
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time Treatment - Week 102	84.6 percentage of participants	—
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time Treatment - Week 108	100 percentage of participants	—
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time Treatment - Week 114	83.3 percentage of participants	—
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time Treatment - Week 120	100 percentage of participants	—
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time Treatment - Week 126	100 percentage of participants	—
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time Treatment - Week 132	100 percentage of participants	—
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time Treatment - Week 138	100 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline through Week 138

Population: ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.

Percentage of participants who filled out an EORTC QLQ-LC13 questionnaire at a visit. The EORTC QLQ-LC13 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis.

Outcome measures

Outcome measures
Measure	Experimental: Alectinib n=79 Participants Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Active Comparator: Premetrexed/Docetaxel n=40 Participants Participants received chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously.
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time Baseline	92.4 percentage of participants	82.5 percentage of participants
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time Treatment - Week 3	96.1 percentage of participants	83.3 percentage of participants
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time Treatment - Week 6	97.2 percentage of participants	63.3 percentage of participants
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time Treatment - Week 12	95.5 percentage of participants	80.0 percentage of participants
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time Treatment - Week 18	88.5 percentage of participants	50.0 percentage of participants
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time Treatment - Week 24	91.1 percentage of participants	100 percentage of participants
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time Treatment - Week 30	96.2 percentage of participants	66.7 percentage of participants
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time Treatment - Week 36	87.8 percentage of participants	66.7 percentage of participants
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time Treatment - Week 42	95.3 percentage of participants	66.7 percentage of participants
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time Treatment - Week 48	100 percentage of participants	100 percentage of participants
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time Treatment - Week 54	97.1 percentage of participants	100 percentage of participants
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time Treatment - Week 60	100 percentage of participants	100 percentage of participants
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time Treatment - Week 66	89.7 percentage of participants	100 percentage of participants
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time Treatment - Week 72	88.9 percentage of participants	100 percentage of participants
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time Treatment - Week 78	84.6 percentage of participants	—
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time Treatment - Week 84	78.3 percentage of participants	—
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time Treatment - Week 90	88.9 percentage of participants	—
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time Treatment - Week 96	100 percentage of participants	—
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time Treatment - Week 102	84.6 percentage of participants	—
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time Treatment - Week 108	100 percentage of participants	—
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time Treatment - Week 114	83.3 percentage of participants	—
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time Treatment - Week 120	80.0 percentage of participants	—
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time Treatment - Week 126	100 percentage of participants	—
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time Treatment - Week 132	100 percentage of participants	—
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time Treatment - Week 138	100 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline through Week 60

Population: ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.

Percentage of participants who filled out an ED-5D-5L questionnaire at a visit. EQ-5D-5L: A generic preference-based health utility measure that provides a single index value for health status. The instrument consists of two parts. The first part, health-state classification, contains five dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.

Outcome measures

Outcome measures
Measure	Experimental: Alectinib n=72 Participants Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Active Comparator: Premetrexed/Docetaxel n=35 Participants Participants received chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously.
Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time Treatment - Week 0	88.9 percentage of participants	82.9 percentage of participants
Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time Treatment - Week 3	86.6 percentage of participants	78.8 percentage of participants
Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time Treatment - Week 6	91.9 percentage of participants	58.6 percentage of participants
Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time Treatment - Week 12	86.8 percentage of participants	80 percentage of participants
Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time Treatment - Week 18	72.1 percentage of participants	66.7 percentage of participants
Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time Treatment - Week 24	82.4 percentage of participants	100 percentage of participants
Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time Treatment - Week 30	80 percentage of participants	66.7 percentage of participants
Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time Treatment - Week 36	80 percentage of participants	50 percentage of participants
Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time Treatment - Week 42	91.7 percentage of participants	50 percentage of participants
Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time Treatment - Week 48	62.5 percentage of participants	0 percentage of participants
Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time Treatment - Week 54	100 percentage of participants	—
Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time Treatment - Week 60	50 percentage of participants	—

SECONDARY outcome

Timeframe: Baseline through study end (up to 33 months)

TTD in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea \[single item and multi-item scales\] chest pain \[single item\], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-LC13.

Outcome measures

Outcome measures
Measure	Experimental: Alectinib n=79 Participants Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Active Comparator: Premetrexed/Docetaxel n=40 Participants Participants received chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously.
Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for ITT Population Coughing score	18.1 months Interval 7.2 to The upper limit of CI was not reached due to an insufficient number of participants with the event.	16.6 months Interval 3.3 to 16.6
Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for ITT Population Dyspnoea score	4.1 months Interval 1.4 to 11.3	3.3 months Interval 1.0 to The upper limit of CI was not reached due to an insufficient number of participants with the event.
Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for ITT Population Pain in chest score	NA months Interval 11.1 to The median and upper limit of CI was not reached due to less number of participants with the event.	NA months Interval 1.6 to The median and upper limit of CI was not reached due to less number of participants with the event.
Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for ITT Population Pain in arm or shoulder score	12.5 months Interval 7.4 to The upper limit of CI was not reached due to less number of participants with the event.	1.9 months Interval 1.6 to The upper limit of CI was not reached due to less number of participants with the event.

SECONDARY outcome

Timeframe: Baseline through study end (up to 33 months)

Population: C-ITT included participants in ITT population with CNS metastasis at baseline (as per IRC assessment). Number analyzed indicates number of participants evaluated for specified categories.

Outcome measures

Outcome measures
Measure	Experimental: Alectinib n=52 Participants Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Active Comparator: Premetrexed/Docetaxel n=28 Participants Participants received chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously.
Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for C-ITT Population Coughing score	NA months Interval 8.3 to The median and upper limit of CI were not reached due to an insufficient number of participants with the event.	16.6 months Interval 1.2 to 16.6
Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for C-ITT Population Dyspnoea score	9.7 months Interval 1.5 to 14.4	1.4 months Interval 0.8 to The upper limit of CI was not reached due to an insufficient number of participants with the event.
Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for C-ITT Population Pain in chest score	NA months Interval 9.7 to The upper limit of CI was not reached due to less number of participants with the event.	NA months Interval 1.4 to The median and upper limit of CI was not reached due to less number of participants with the event.
Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for C-ITT Population Pain in arm or shoulder score	11.1 months Interval 4.1 to The upper limit of CI was not reached due to less number of participants with the event.	1.7 months Interval 0.9 to The upper limit of CI was not reached due to less number of participants with the event.

SECONDARY outcome

Timeframe: Baseline through study end (up to 33 months)

Population: ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.

Outcome measures

Outcome measures
Measure	Experimental: Alectinib n=79 Participants Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Active Comparator: Premetrexed/Docetaxel n=40 Participants Participants received chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously.
Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for ITT Population Dyspnoea score	13.3 months Interval 2.9 to The upper limit of CI was not reached due to an insufficient number of participants with the event.	8.3 months Interval 1.2 to 8.3
Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for ITT Population Fatigue score	5.6 months Interval 1.4 to The upper limit of CI was not reached due to an insufficient number of participants with the event.	1.2 months Interval 0.8 to The upper limit of CI was not reached due to an insufficient number of participants with the event.

SECONDARY outcome

Timeframe: Baseline through study end (up to 33 months)

Population: C-ITT included participants in ITT population with CNS metastasis at baseline (as per IRC assessment).

Outcome measures

Outcome measures
Measure	Experimental: Alectinib n=52 Participants Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Active Comparator: Premetrexed/Docetaxel n=26 Participants Participants received chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously.
Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for C-ITT Population Dyspnoea score	16.6 months Interval 2.9 to The upper limit of CI was not reached due to an insufficient number of participants with the event.	8.3 months Interval 1.0 to 8.3
Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for C-ITT Population Fatigue score	14.4 months Interval 2.6 to The upper limit of CI was not reached due to less number of participants with the event.	1.0 months Interval 0.8 to The upper limit of CI was not reached due to less number of participants with the event.

SECONDARY outcome

Timeframe: Baseline through study end (up to 33 months)

Population: C-ITT included participants in ITT population with CNS metastasis at baseline (as per IRC assessment).

TTD for a composite of three symptoms (cough, dyspnea, chest pain) in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for any component of the composite of the three following symptoms \[cough, dyspnea \[multi-item subscales QLQ-LC13\] and chest pain\]) as measured by the EORTC QLQ-LC13.

Outcome measures

Outcome measures
Measure	Experimental: Alectinib n=52 Participants Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Active Comparator: Premetrexed/Docetaxel n=28 Participants Participants received chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously.
TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for C-ITT Population	2.8 months Interval 0.9 to 5.6	1.4 months Interval 0.8 to The upper CT limit could not be estimated due to an insufficient number of participants with the event

SECONDARY outcome

Timeframe: Baseline through study end (up to 33 months)

Population: ITT population included all participants randomized in the study, irrespective of whether or not they received study drug.

Outcome measures

Outcome measures
Measure	Experimental: Alectinib n=79 Participants Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Active Comparator: Premetrexed/Docetaxel n=40 Participants Participants received chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously.
TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for ITT Population	1.4 months Interval 0.9 to 4.2	1.4 months Interval 0.9 to 4.2

SECONDARY outcome

Timeframe: Baseline through study end (up to 33 months)

Population: Safety (SAF) population included all participants who received at least one dose of any study drug.

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.

Outcome measures

Outcome measures
Measure	Experimental: Alectinib n=77 Participants Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Active Comparator: Premetrexed/Docetaxel n=37 Participants Participants received chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously.
Percentage of Participants With Adverse Events (AEs)	89.6 Percentage of Participants	89.2 Percentage of Participants

Adverse Events

Experimental: Alectinib

Serious events: 20 serious events

Other events: 57 other events

Deaths: 26 deaths

Active Comparator: Premetrexed/Docetaxel

Serious events: 7 serious events

Other events: 31 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Communications

Hoffmann-La Roche

Phone: 1-800-821-8590

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Experimental: Alectinib n=77 participants at risk Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Active Comparator: Premetrexed/Docetaxel n=37 participants at risk Participants received chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously.
Blood and lymphatic system disorders Anaemia	0.00% 0/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	5.4% 2/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	5.4% 2/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Blood and lymphatic system disorders Neutropenia	0.00% 0/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	2.7% 1/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Cardiac disorders Myocardial infarction	1.3% 1/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Gastrointestinal disorders Abdominal pain	1.3% 1/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	2.7% 1/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Gastrointestinal disorders Diarrhoea	0.00% 0/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	2.7% 1/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Gastrointestinal disorders Nausea	0.00% 0/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	2.7% 1/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Gastrointestinal disorders Stomatitis	0.00% 0/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	2.7% 1/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Hepatobiliary disorders Cholelithiasis	1.3% 1/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Infections and infestations Abscess jaw	1.3% 1/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Infections and infestations Bronchitis	1.3% 1/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Infections and infestations Lung infection	0.00% 0/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	2.7% 1/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Infections and infestations Pneumonia	5.2% 4/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Infections and infestations Pneumonia bacterial	0.00% 0/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	2.7% 1/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Injury, poisoning and procedural complications Ankle fracture	1.3% 1/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Injury, poisoning and procedural complications Jaw fracture	1.3% 1/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Injury, poisoning and procedural complications Skull fractured base	1.3% 1/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Investigations Blood creatine phosphokinase increased	1.3% 1/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	1.3% 1/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Nervous system disorders Cerebellar ataxia	1.3% 1/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Nervous system disorders Epilepsy	1.3% 1/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Nervous system disorders Syncope	1.3% 1/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Psychiatric disorders Depression	1.3% 1/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Renal and urinary disorders Acute kidney injury	2.6% 2/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Respiratory, thoracic and mediastinal disorders Haemoptysis	1.3% 1/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Vascular disorders Deep vein thrombosis	1.3% 1/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Infections and infestations Diverticulitis	1.3% 1/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Infections and infestations Erysipelas	1.3% 1/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Infections and infestations H1N1 Influenza	1.3% 1/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Infections and infestations Pharyngitis	1.3% 1/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Infections and infestations Gastroenteritis	0.00% 0/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	2.7% 1/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Injury, poisoning and procedural complications Wound Complication	1.3% 1/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Investigations Blood Creatinine Increased	1.3% 1/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Vascular disorders Hypertension	1.3% 1/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
General disorders Death	1.3% 1/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Musculoskeletal and connective tissue disorders Osteoporotic fracture	1.3% 1/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.

Measure	Experimental: Alectinib n=77 participants at risk Participants received oral alectinib at a dose of 600 milligrams (mg) twice daily, taken with food and treatment continued until disease progression, unacceptable toxicity, withdrawal of consent or death.	Active Comparator: Premetrexed/Docetaxel n=37 participants at risk Participants received chemotherapy with either pemetrexed (500 milligrams per square meter \[mg/m\^2\] of body surface area) or docetaxel (75 mg/m\^2) intravenously.
Blood and lymphatic system disorders Anaemia	15.6% 12/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	10.8% 4/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Blood and lymphatic system disorders Neutropenia	0.00% 0/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	10.8% 4/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Gastrointestinal disorders Constipation	20.8% 16/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	10.8% 4/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Gastrointestinal disorders Diarrhoea	6.5% 5/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	5.4% 2/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Gastrointestinal disorders Nausea	3.9% 3/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	16.2% 6/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Gastrointestinal disorders Vomiting	3.9% 3/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	5.4% 2/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
General disorders Asthenia	11.7% 9/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	16.2% 6/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
General disorders Fatigue	6.5% 5/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	24.3% 9/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
General disorders Oedema peripheral	14.3% 11/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	5.4% 2/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
General disorders Pyrexia	3.9% 3/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	8.1% 3/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Investigations Blood bilirubin increased	7.8% 6/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Metabolism and nutrition disorders Decreased appetite	9.1% 7/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	10.8% 4/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Musculoskeletal and connective tissue disorders Back pain	13.0% 10/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	5.4% 2/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Musculoskeletal and connective tissue disorders Myalgia	14.3% 11/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	10.8% 4/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	2.6% 2/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	5.4% 2/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Nervous system disorders Dizziness	3.9% 3/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	5.4% 2/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Nervous system disorders Headache	6.5% 5/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	8.1% 3/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Nervous system disorders Neuropathy peripheral	1.3% 1/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	5.4% 2/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Respiratory, thoracic and mediastinal disorders Cough	10.4% 8/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	10.8% 4/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	11.7% 9/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Skin and subcutaneous tissue disorders Alopecia	1.3% 1/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	21.6% 8/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Skin and subcutaneous tissue disorders Pruritus Generalised	0.00% 0/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	8.1% 3/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Ear and labyrinth disorders Tinnitus	2.6% 2/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	5.4% 2/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Gastrointestinal disorders Abdominal Pain	6.5% 5/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Immune system disorders Drug Hypersensitivity	0.00% 0/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	5.4% 2/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Infections and infestations Bronchitis	6.5% 5/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	2.7% 1/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Infections and infestations Nasopharyngitis	5.2% 4/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	2.7% 1/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Infections and infestations Pneumonia	7.8% 6/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Infections and infestations Upper Respiratory Tract Infection	9.1% 7/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	2.7% 1/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Investigations Blood Creatinine Increased	6.5% 5/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Investigations Electrocardiogram QT Prolonged	5.2% 4/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	0.00% 0/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Musculoskeletal and connective tissue disorders Arthralgia	5.2% 4/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	8.1% 3/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal Chest Pain	2.6% 2/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	5.4% 2/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.
Nervous system disorders Paraesthesia	1.3% 1/77 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.	8.1% 3/37 • Approximately 15 months SAF population included all participants who received at least one dose of any study drug.