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

• ClinicalTrials.gov Identifier: NCT02075840
• Recruitment Status: Active, not recruiting
• First Posted: March 3, 2014
• Results First Posted: March 15, 2018
• Last Update Posted: May 14, 2024
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-Small Cell Lung Cancer
• Interventions: Drug: Alectinib; Drug: Crizotinib
• Enrollment: 303

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.
Pre-assignment Details	A total of 303 participants were randomized at the time of clinical cut-off (CCO) date on 9 February 2017 and included in the intent-to-treat (ITT) population; 152 participants in the alectinib arm and 151 participants in the crizotinib arm.

Arm/Group Title	Alectinib	Crizotinib
Arm/Group Description	Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received crizotinib at 250 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
Period Title: Overall Study
Started	152	151
Completed	0	0
Not Completed	152	151
Reason Not Completed
Withdrawal by Subject	13	22
Reason not specified	1	0
Adverse Event	0	2
Death	35	40
Lost to Follow-up	3	2
Physician Decision	1	3
Ongoing at CCOD	99	82

Baseline Characteristics

Arm/Group Title		Alectinib	Crizotinib	Total
Arm/Group Description		Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received crizotinib at 250 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.	Total of all reporting groups
Overall Number of Baseline Participants		152	151	303
Baseline Analysis Population Description		Analysis was performed on intent to treat (ITT) population which included all randomized participants in the study.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	152 participants	151 participants	303 participants
		56.3 (12.0)	53.8 (13.5)	55.1 (12.8)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	152 participants	151 participants	303 participants
	Female	84 55.3%	87 57.6%	171 56.4%
	Male	68 44.7%	64 42.4%	132 43.6%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	152 participants	151 participants	303 participants
Ethnicity - Hispanic or Latino		8	8	16
Ethinicity - Not Hispanic or Latino		138	136	274
Ethnicity - Not Stated		6	7	13
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	152 participants	151 participants	303 participants
Race - American Indian or Alaska Native		4	0	4
Race - Asian		69	69	138
Race - Black or African American		0	4	4
Race - Native Hawaiian or other Pacific Islander		1	1	2
Race - White		76	75	151
Race - Unknown		2	2	4

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS) by Investigator Assessment
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Alectinib	Crizotinib
Arm/Group Description:	Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received crizotinib at 250 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed	152	151
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (17.7 to NA)	11.1; (9.1 to 13.1)

[1]

The median PFS had not been reached in the alectinib arm at the time of data cutoff date (9 Feb 2017).

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib, Crizotinib
	Comments	Stratified hazard ratio and p-value are stratified for covariates Race (Asian vs Non-Asian) and CNS metastases at baseline by IRC.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio, stratified
	Estimated Value	0.47
	Confidence Interval	(2-Sided) 95%; 0.34 to 0.65
	Estimation Comments	[Not Specified]

2. Primary Outcome

Title	Percentage of Participants With PFS Event by Investigator Assessment
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Alectinib	Crizotinib
Arm/Group Description:	Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received crizotinib at 250 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed	152	151
Measure Type: Number; Unit of Measure: Percentage of Participants
	40.8	67.5

3. Secondary Outcome

Title	PFS Independent Review Committee (IRC)-Assessed
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Alectinib	Crizotinib
Arm/Group Description:	Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received crizotinib at 250 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed	152	151
Median (95% Confidence Interval); Unit of Measure: months
	25.7 [1]; (19.9 to NA)	10.4; (7.7 to 14.6)

[1]

The upper limit of the CI could not be estimated in the alectinib arm at the time of data cutoff date (9 Feb 2017).

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib, Crizotinib
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Stratified hazard ratio and p-value are stratified for covariates Race (Asian vs Non-Asian) and CNS metastases at baseline by IRC.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.50
	Confidence Interval	(2-Sided) 95%; 0.36 to 0.70
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Percentage of Participants With PFS Event by IRC
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Alectinib	Crizotinib
Arm/Group Description:	Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received crizotinib at 250 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed	152	151
Measure Type: Number; Unit of Measure: Percentage of Participants
	41.4	60.9

5. Secondary Outcome

Title	Percentage of Participants With Central Nervous System (CNS) Progression as Determined by IRC Using RECIST V1.1 Criteria
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Alectinib	Crizotinib
Arm/Group Description:	Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received crizotinib at 250 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed	152	151
Measure Type: Number; Unit of Measure: Percentage of Participants
	11.8	45.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib, Crizotinib
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	IRC, RECIST v1.1 Stratified Analysis (by race (Asian vs non-Asian) and CNS metastases at baseline by IRC)
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Cause-Specific Hazard Ratio
	Estimated Value	0.16
	Confidence Interval	(2-Sided) 95%; 0.10 to 0.28
	Estimation Comments	[Not Specified]

6. Secondary Outcome

Title	Percentage of Participants With Central Nervous System (CNS) Progression as Determined by IRC Using Revised Assessment in Neuro Oncology (RANO) Criteria
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Alectinib	Crizotinib
Arm/Group Description:	Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received crizotinib at 250 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed	152	151
Measure Type: Number; Unit of Measure: Percentage of Participants
	10.5	35.8

7. Secondary Outcome

Title	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
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Alectinib	Crizotinib
Arm/Group Description:	Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received crizotinib at 250 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed	152	151
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
	82.9; (75.95 to 88.51)	75.5; (67.84 to 82.12)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib, Crizotinib
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0936
	Comments	Stratified analysis
	Method	Mantel Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Overall Response Rates
	Estimated Value	7.40
	Confidence Interval	(2-Sided) 95%; -1.71 to 16.50
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	Duration of Response (DOR) According to RECIST V1.1 Criteria as Assessed by the Investigators
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Alectinib	Crizotinib
Arm/Group Description:	Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received crizotinib at 250 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed	152	151
Median (95% Confidence Interval); Unit of Measure: Months
	NA [1]; (NA to NA)	11.1; (7.9 to 13.0)

[1]

The median DOR was not estimable [95% CI: NE] in the alectinib arm due to the low number of contributing events of disease progression or death.

9. Secondary Outcome

Title	Overall Survival (OS)
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Alectinib	Crizotinib
Arm/Group Description:	Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received crizotinib at 250 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed	152	151
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (NA to NA)	NA [1]; (NA to NA)

[1]

Median time to OS event was not reached in participants in either treatment arm at the time of data cutoff (9 Feb 2017).

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib, Crizotinib
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2405
	Comments	Stratified analysis
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.76
	Confidence Interval	(2-Sided) 95%; 0.48 to 1.20
	Estimation Comments	[Not Specified]

10. Secondary Outcome

Title	Percentage of Participants With OS Event
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Alectinib	Crizotinib
Arm/Group Description:	Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received crizotinib at 250 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed	152	151
Measure Type: Number; Unit of Measure: Percentage of Participants
	23.0	26.5

11. Secondary Outcome

Title	Percentage of Participants With CNS ORR of CR or PR IRC-assessed According to RECIST v1.1 Criteria
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title		Alectinib	Crizotinib
Arm/Group Description:		Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received crizotinib at 250 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed		152	151
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
Measurable CNS lesions at baseline	Number Analyzed	21 participants	22 participants
		81.0; (58.09 to 94.55)	50.0; (28.22 to 71.78)
Measurable and non-measurable CNS lesions	Number Analyzed	64 participants	58 participants
		59.4; (46.37 to 71.49)	25.9; (15.26 to 39.04)

12. Secondary Outcome

Title	CNS DOR IRC-assessed According to RECIST v1.1 Criteria
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Alectinib	Crizotinib
Arm/Group Description:	Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received crizotinib at 250 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed	21	22
Median (95% Confidence Interval); Unit of Measure: months
	17.3 [1]; (14.8 to NA)	5.5; (2.1 to 17.3)

[1]

The upper limit of the CI for CNS DOR could not be estimated at time of the data cutoff for participants in the alectinib arm.

13. Secondary Outcome

Title	Percentage of Participants With Adverse Events
Description	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Alectinib	Crizotinib
Arm/Group Description:	Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received crizotinib at 250 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed	152	151
Measure Type: Number; Unit of Measure: Percentage of Participants
	97.0	97.0

14. Secondary Outcome

Title	Area Under The Concentration-Time Curve (AUC) of Alectinib
Description	[Not Specified]
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)

Outcome Measure Data

Analysis Population Description

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/Group Title		Alectinib
Arm/Group Description:		Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed		144
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hr*ng/mL
Baseline	Number Analyzed	10 participants
		713; (104.9%)
Treatment - week 4	Number Analyzed	9 participants
		5030; (47.2%)

15. Secondary Outcome

Title	Maximum Concentration (Cmax) of Alectinib
Description	[Not Specified]
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)

Outcome Measure Data

Analysis Population Description

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/Group Title		Alectinib
Arm/Group Description:		Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed		144
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nanogram/milliliter (ng/mL)
Baseline	Number Analyzed	10 participants
		211; (55.5%)
Treatment - week 4	Number Analyzed	9 participants
		717; (46.8%)

16. Secondary Outcome

Title	Time to Reach Cmax (Tmax) of Alectinib
Description	[Not Specified]
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)

Outcome Measure Data

Analysis Population Description

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/Group Title		Alectinib
Arm/Group Description:		Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed		144
Median (Full Range); Unit of Measure: hours
Baseline	Number Analyzed	10 participants
		6.03; (1.98 to 12.00)
Treatment - week 4	Number Analyzed	9 participants
		4.02; (2.00 to 8.00)

17. Secondary Outcome

Title	AUC of Alectinib Metabolite
Description	[Not Specified]
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)

Outcome Measure Data

Analysis Population Description

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/Group Title		Alectinib
Arm/Group Description:		Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed		144
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: hr*ng/mL
Baseline	Number Analyzed	10 participants
		142; (191.7%)
Treatment - week 4	Number Analyzed	9 participants
		2230; (37.0%)

18. Secondary Outcome

Title	Cmax of Alectinib Metabolite
Description	[Not Specified]
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)

Outcome Measure Data

Analysis Population Description

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/Group Title		Alectinib
Arm/Group Description:		Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed		144
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nanogram/milliliter (ng/mL)
Baseline	Number Analyzed	10 participants
		56.2; (80.1%)
Treatment - week 4	Number Analyzed	9 participants
		321; (32.0%)

19. Secondary Outcome

Title	Tmax of Alectinib Metabolite
Description	[Not Specified]
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)

Outcome Measure Data

Analysis Population Description

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/Group Title		Alectinib
Arm/Group Description:		Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed		144
Median (Full Range); Unit of Measure: hours
Baseline	Number Analyzed	10 participants
		8.00; (5.98 to 12.00)
Treatment - week 4	Number Analyzed	9 participants
		6.00; (2.00 to 10.00)

20. Secondary Outcome

Title	Time to Deterioration by European Organization for The Research And Treatment of Cancer (EORTC) Quality Of Life Questionnaire Core 30 (C30)
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Alectinib	Crizotinib
Arm/Group Description:	Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received crizotinib at 250 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed	152	151
Median (95% Confidence Interval); Unit of Measure: months
Fatigue	NA [1]; (NA to NA)	NA [1]; (9.4 to NA)
Dyspnea	NA [1]; (NA to NA)	NA [1]; (NA to NA)

[1]

Median deterioration not reached at CCOD

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib, Crizotinib
	Comments	Fatigue
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2079
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Stratified analysis
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.74
	Confidence Interval	(2-Sided) 95%; 0.46 to 1.19
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alectinib, Crizotinib
	Comments	Dyspnea
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.1137
	Comments	Stratified analysis
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.66
	Confidence Interval	(2-Sided) 95%; 0.88 to 3.15
	Estimation Comments	[Not Specified]

21. Secondary Outcome

Title	Percentage of Participants With Deterioration by EORTC Quality Of Life Questionnaire Core 30 (C30)
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Alectinib	Crizotinib
Arm/Group Description:	Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received crizotinib at 250 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed	152	151
Measure Type: Number; Unit of Measure: Percentage of Participants
Fatigue	21.7	25.2
Dyspnea	17.1	9.9

22. Secondary Outcome

Title	Time to Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13)
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Alectinib	Crizotinib
Arm/Group Description:	Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received crizotinib at 250 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed	152	151
Median (95% Confidence Interval); Unit of Measure: months
Coughing	NA [1]; (24.0 to NA)	NA [1]; (NA to NA)
Dyspnea	22.8 [2]; (11.8 to NA)	NA [1]; (21.0 to NA)
Pain in arm and shoulder	NA [1]; (NA to NA)	NA [1]; (NA to NA)
Pain in chest	NA [1]; (NA to NA)	NA [1]; (NA to NA)
Composite score (c, p in c, d)	12.7 [2]; (5.0 to NA)	21.0 [2]; (9.8 to NA)

[1]

Median deterioration not reached at CCOD

[2]

Upper limit of the CI not reached at CCOD

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Alectinib, Crizotinib
	Comments	Coughing
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.7042
	Comments	Stratified analysis
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95%; 0.44 to 1.74
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Alectinib, Crizotinib
	Comments	Dyspnea
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0285
	Comments	Stratified analysis
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.76
	Confidence Interval	(2-Sided) 95%; 1.05 to 2.92
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Alectinib, Crizotinib
	Comments	Pain in arm and shoulder
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2377
	Comments	Stratified analysis
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.43
	Confidence Interval	(2-Sided) 95%; 0.79 to 2.61
	Estimation Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Alectinib, Crizotinib
	Comments	Pain in chest
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0796
	Comments	Stratified analysis
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.51
	Confidence Interval	(2-Sided) 95%; 0.24 to 1.10
	Estimation Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Alectinib, Crizotinib
	Comments	Composite score
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6435
	Comments	Stratified analysis
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.10
	Confidence Interval	(2-Sided) 95%; 0.72 to 1.68
	Estimation Comments	[Not Specified]

23. Secondary Outcome

Title	Percentage of Participants With Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13)
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Alectinib	Crizotinib
Arm/Group Description:	Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received crizotinib at 250 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed	152	151
Measure Type: Number; Unit of Measure: Percentage of Participants
Coughing	11	11
Dyspnea	28	16
Pain in arm and shoulder	18	12
Pain in chest	7	11
Composite score (c, p in c, d)	32	28

24. Secondary Outcome

Title	Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title		Alectinib	Crizotinib
Arm/Group Description:		Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received crizotinib at 250 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed		152	151
Median (Full Range); Unit of Measure: Score on a scale
Baseline	Number Analyzed	100 participants	97 participants
		66.67; (8.3 to 100.0)	66.67; (0.0 to 100.0)
Treatment - week 4	Number Analyzed	95 participants	89 participants
		66.67; (0.0 to 100.0)	66.67; (16.7 to 100.0)
Treatment - week 8	Number Analyzed	89 participants	84 participants
		75.0; (16.7 to 100.0)	75.0; (16.7 to 100.0)
Treatment - week 12	Number Analyzed	75 participants	78 participants
		75.0; (25.0 to 100.0)	75.0; (33.3 to 100.0)
Treatment - week 16	Number Analyzed	79 participants	73 participants
		75.0; (16.7 to 100.0)	83.33; (16.7 to 100.0)
Treatment - week 20	Number Analyzed	73 participants	67 participants
		75.0; (16.7 to 100.0)	75.0; (16.7 to 100.0)
Treatment - week 24	Number Analyzed	77 participants	71 participants
		75.0; (16.7 to 100.0)	83.33; (8.3 to 100.0)
Treatment - week 28	Number Analyzed	67 participants	62 participants
		75.0; (33.3 to 100.0)	75.0; (33.3 to 100.0)
Treatment - week 32	Number Analyzed	73 participants	65 participants
		75.0; (33.3 to 100.0)	66.67; (8.3 to 100.0)
Treatment - week 36	Number Analyzed	64 participants	61 participants
		79.17; (16.7 to 100.0)	66.67; (16.7 to 100.0)
Treatment - week 40	Number Analyzed	74 participants	50 participants
		75.0; (16.7 to 100.0)	83.33; (33.3 to 100.0)
Treatment - week 44	Number Analyzed	62 participants	47 participants
		83.33; (16.7 to 100.0)	83.33; (16.7 to 100.0)
Treatment - week 48	Number Analyzed	67 participants	47 participants
		66.67; (25.0 to 100.0)	83.33; (41.7 to 100.0)
Treatment - week 52	Number Analyzed	58 participants	44 participants
		83.33; (16.7 to 100.0)	75.00; (41.7 to 100.0)
Treatment - week 56	Number Analyzed	61 participants	48 participants
		75.0; (16.7 to 100.0)	75.0; (41.7 to 100.0)
Treatment - week 60	Number Analyzed	47 participants	39 participants
		75.0; (33.3 to 100.0)	75.0; (50.0 to 100.0)
Treatment - week 64	Number Analyzed	55 participants	39 participants
		75.0; (33.3 to 100.0)	83.33; (41.7 to 100.0)
Treatment - week 68	Number Analyzed	49 participants	34 participants
		75.0; (33.3 to 100.0)	79.17; (33.3 to 100.0)
Treatment - week 72	Number Analyzed	54 participants	34 participants
		75.0; (33.3 to 100.0)	75.00; (8.3 to 100.0)
Treatment - week 76	Number Analyzed	42 participants	29 participants
		75.0; (41.7 to 100.0)	75.0; (16.7 to 100.0)
Treatment - week 80	Number Analyzed	43 participants	23 participants
		75.0; (33.3 to 100.0)	75.0; (33.3 to 100.0)
Treatment - week 84	Number Analyzed	33 participants	19 participants
		83.33; (41.7 to 100.0)	66.67; (33.3 to 100.0)
Treatment - week 88	Number Analyzed	36 participants	16 participants
		75.0; (33.3 to 100.0)	66.67; (33.3 to 100.0)
Treatment - week 92	Number Analyzed	30 participants	13 participants
		70.83; (33.3 to 100.0)	75.0; (50.0 to 100.0)
Treatment - week 96	Number Analyzed	22 participants	11 participants
		66.67; (33.3 to 100.0)	66.67; (33.3 to 100.0)
Treatment - week 100	Number Analyzed	18 participants	10 participants
		66.67; (25.0 to 100.0)	75.0; (33.3 to 100.0)
Treatment - week 104	Number Analyzed	15 participants	7 participants
		66.67; (50.0 to 100.0)	66.67; (50.0 to 100.0)
Treatment - week 108	Number Analyzed	11 participants	7 participants
		66.67; (50.0 to 100.0)	75.0; (33.3 to 100.0)
Treatment - week 112	Number Analyzed	9 participants	4 participants
		75.0; (50.0 to 100.0)	75.0; (33.3 to 100.0)
Treatment - week 116	Number Analyzed	4 participants	2 participants
		70.83; (41.7 to 100.0)	91.67; (83.3 to 100.0)
Treatment - week 120	Number Analyzed	3 participants	151 participants
		83.3; (50.0 to 100.0)	NA [1]; (NA to NA)

[1]

Not evaluable at week 120

25. Secondary Outcome

Title	HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title		Alectinib	Crizotinib
Arm/Group Description:		Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received crizotinib at 250 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed		152	151
Median (Full Range); Unit of Measure: Score on a scale
Baseline	Number Analyzed	100 participants	96 participants
		33.33; (0.0 to 100.0)	33.33; (0.0 to 100.0)
Treatment - week 4	Number Analyzed	95 participants	89 participants
		33.33; (0.0 to 100.0)	33.33; (0.0 to 100.0)
Treatment - week 8	Number Analyzed	89 participants	84 participants
		33.33; (0.0 to 66.7)	33.33; (0.0 to 100.0)
Treatment - week 12	Number Analyzed	75 participants	78 participants
		33.33; (0.0 to 100.0)	0.0; (0.0 to 66.7)
Treatment - week 16	Number Analyzed	79 participants	73 participants
		0.0; (0.0 to 100.0)	0.0; (0.0 to 66.7)
Treatment - week 20	Number Analyzed	73 participants	67 participants
		33.33; (0.0 to 100.0)	0.0; (0.0 to 66.7)
Treatment - week 24	Number Analyzed	77 participants	71 participants
		33.33; (0.0 to 100.0)	33.33; (0.0 to 100.0)
Treatment - week 28	Number Analyzed	67 participants	62 participants
		33.33; (0.0 to 100.0)	16.67; (0.0 to 100.0)
Treatment - week 32	Number Analyzed	73 participants	65 participants
		33.33; (0.0 to 100.0)	33.33; (0.0 to 100.0)
Treatment - week 36	Number Analyzed	64 participants	61 participants
		0.0; (0.0 to 100.0)	0.0; (0.0 to 66.7)
Treatment - week 40	Number Analyzed	74 participants	50 participants
		33.33; (0.0 to 66.7)	0.0; (0.0 to 66.7)
Treatment - week 44	Number Analyzed	62 participants	47 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 66.7)
Treatment - week 48	Number Analyzed	67 participants	47 participants
		33.33; (0.0 to 66.7)	0.0; (0.0 to 66.7)
Treatment - week 52	Number Analyzed	58 participants	44 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 33.3)
Treatment - week 56	Number Analyzed	61 participants	48 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 100.0)
Treatment - week 60	Number Analyzed	47 participants	39 participants
		33.33; (0.0 to 100.0)	0.0; (0.0 to 66.7)
Treatment - week 64	Number Analyzed	55 participants	39 participants
		33.33; (0.0 to 66.7)	0.0; (0.0 to 66.7)
Treatment - week 68	Number Analyzed	49 participants	34 participants
		33.33; (0.0 to 66.7)	0.0; (0.0 to 66.7)
Treatment - week 72	Number Analyzed	54 participants	34 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 66.7)
Treatment - week 76	Number Analyzed	42 participants	29 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 66.7)
Treatment - week 80	Number Analyzed	43 participants	23 participants
		33.33; (0.0 to 66.7)	0.0; (0.0 to 33.33)
Treatment - week 84	Number Analyzed	33 participants	19 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 33.33)
Treatment - week 88	Number Analyzed	36 participants	16 participants
		33.33; (0.0 to 100.0)	0.0; (0.0 to 33.33)
Treatment - week 92	Number Analyzed	30 participants	13 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 66.7)
Treatment - week 96	Number Analyzed	22 participants	11 participants
		16.67; (0.0 to 66.7)	0.0; (0.0 to 33.33)
Treatment - week 100	Number Analyzed	18 participants	10 participants
		0.0; (0.0 to 100.0)	0.0; (0.0 to 33.3)
Treatment - week 104	Number Analyzed	15 participants	7 participants
		33.33; (0.0 to 66.7)	0.0; (0.0 to 33.3)
Treatment - week 108	Number Analyzed	11 participants	7 participants
		33.33; (0.0 to 66.7)	33.33; (0.0 to 33.33)
Treatment - week 112	Number Analyzed	9 participants	4 participants
		33.33; (0.0 to 33.33)	0.0; (0.0 to 33.33)
Treatment - week 116	Number Analyzed	4 participants	2 participants
		33.33; (0.0 to 33.33)	16.67; (0.0 to 33.33)
Treatment - week 120	Number Analyzed	3 participants	0 participants
		33.33; (33.33 to 33.33)

26. Secondary Outcome

Title	HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title		Alectinib	Crizotinib
Arm/Group Description:		Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received crizotinib at 250 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed		152	151
Median (Full Range); Unit of Measure: Score on a scale
Baseline	Number Analyzed	100 participants	96 participants
		22.22; (0.0 to 100.0)	22.22; (0.0 to 100.0)
Treatment - Week 4	Number Analyzed	95 participants	89 participants
		22.22; (0.0 to 100.0)	22.22; (0.0 to 88.9)
Treatment - Week 8	Number Analyzed	89 participants	84 participants
		22.22; (0.0 to 66.7)	11.11; (0.0 to 66.7)
Treatment - Week 12	Number Analyzed	75 participants	78 participants
		22.22; (0.0 to 66.7)	11.11; (0.0 to 66.7)
Treatment - Week 16	Number Analyzed	79 participants	73 participants
		22.22; (0.0 to 77.8)	11.11; (0.0 to 88.9)
Treatment - Week 20	Number Analyzed	73 participants	67 participants
		22.22; (0.0 to 88.9)	11.11; (0.0 to 66.7)
Treatment - Week 24	Number Analyzed	77 participants	71 participants
		22.22; (0.0 to 77.8)	11.11; (0.0 to 77.8)
Treatment - Week 28	Number Analyzed	67 participants	62 participants
		11.11; (0.0 to 44.4)	11.11; (0.0 to 100.0)
Treatment - Week 32	Number Analyzed	73 participants	65 participants
		22.22; (0.0 to 66.7)	11.11; (0.0 to 88.9)
Treatment - Week 36	Number Analyzed	64 participants	61 participants
		16.67; (0.0 to 77.8)	11.11; (0.0 to 66.7)
Treatment - Week 40	Number Analyzed	74 participants	50 participants
		11.11; (0.0 to 55.6)	5.56; (0.0 to 66.7)
Treatment - Week 44	Number Analyzed	62 participants	47 participants
		11.11; (0.0 to 88.9)	11.11; (0.0 to 77.8)
Treatment - Week 48	Number Analyzed	67 participants	47 participants
		22.22; (0.0 to 55.6)	11.11; (0.0 to 44.4)
Treatment - Week 52	Number Analyzed	58 participants	44 participants
		22.22; (0.0 to 44.4)	11.11; (0.0 to 66.7)
Treatment - Week 56	Number Analyzed	61 participants	48 participants
		22.22; (0.0 to 77.8)	11.11; (0.0 to 77.8)
Treatment - Week 60	Number Analyzed	47 participants	39 participants
		22.22; (0.0 to 77.8)	0.0; (0.0 to 55.6)
Treatment - Week 64	Number Analyzed	55 participants	39 participants
		22.22; (0.0 to 66.7)	11.11; (0.0 to 66.7)
Treatment - Week 68	Number Analyzed	49 participants	34 participants
		22.22; (0.0 to 77.8)	11.11; (0.0 to 55.6)
Treatment - Week 72	Number Analyzed	54 participants	34 participants
		22.22; (0.0 to 66.7)	11.11; (0.0 to 44.4)
Treatment - Week 76	Number Analyzed	42 participants	29 participants
		11.11; (0.0 to 66.7)	11.11; (0.0 to 55.6)
Treatment - Week 80	Number Analyzed	43 participants	23 participants
		22.22; (0.0 to 66.7)	11.11; (0.0 to 55.6)
Treatment - Week 84	Number Analyzed	33 participants	19 participants
		11.11; (0.0 to 66.7)	11.11; (0.0 to 44.4)
Treatment - Week 88	Number Analyzed	36 participants	16 participants
		22.22; (0.0 to 55.6)	22.22; (0.0 to 33.3)
Treatment - Week 92	Number Analyzed	30 participants	13 participants
		22.22; (0.0 to 44.4)	22.22; (0.0 to 77.8)
Treatment - Week 96	Number Analyzed	22 participants	11 participants
		22.22; (0.0 to 66.7)	22.22; (0.0 to 44.4)
Treatment - Week 100	Number Analyzed	18 participants	10 participants
		22.22; (0.0 to 55.6)	27.78; (0.0 to 44.4)
Treatment - Week 104	Number Analyzed	15 participants	7 participants
		11.11; (0.0 to 66.7)	11.11; (0.0 to 33.3)
Treatment - Week 108	Number Analyzed	11 participants	7 participants
		22.22; (0.0 to 66.7)	11.11; (0.0 to 33.3)
Treatment - Week 112	Number Analyzed	9 participants	4 participants
		11.11; (11.11 to 44.4)	27.78; (0.0 to 33.3)
Treatment - Week 116	Number Analyzed	4 participants	2 participants
		16.67; (11.1 to 22.2)	16.67; (0.0 to 33.3)
Treatment - Week 120	Number Analyzed	3 participants	0 participants
		22.22; (11.1 to 33.3)

27. Secondary Outcome

Title	HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title		Alectinib	Crizotinib
Arm/Group Description:		Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received crizotinib at 250 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed		152	151
Median (Full Range); Unit of Measure: Score on a scale
Baseline	Number Analyzed	100 participants	96 participants
		33.33; (0.0 to 100.0)	0.0; (0.0 to 100.0)
Treatment - Week 4	Number Analyzed	95 participants	89 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 66.7)
Treatment - Week 8	Number Analyzed	89 participants	84 participants
		0.0; (0.0 to 33.3)	0.0; (0.0 to 66.7)
Treatment - Week 12	Number Analyzed	75 participants	78 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 66.7)
Treatment - Week 16	Number Analyzed	79 participants	73 participants
		0.0; (0.0 to 33.3)	0.0; (0.0 to 66.7)
Treatment - Week 20	Number Analyzed	73 participants	67 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 66.7)
Treatment - Week 24	Number Analyzed	77 participants	71 participants
		0.0; (0.0 to 33.3)	0.0; (0.0 to 66.7)
Treatment - Week 28	Number Analyzed	67 participants	62 participants
		0.0; (0.0 to 33.3)	0.0; (0.0 to 33.3)
Treatment - Week 32	Number Analyzed	73 participants	65 participants
		0.00; (0.0 to 66.7)	0.0; (0.0 to 66.7)
Treatment - Week 36	Number Analyzed	64 participants	61 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 33.3)
Treatment - Week 40	Number Analyzed	74 participants	50 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 66.7)
Treatment - Week 44	Number Analyzed	62 participants	47 participants
		0.0; (0.0 to 100.0)	0.0; (0.0 to 66.7)
Treatment - Week 48	Number Analyzed	67 participants	47 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 33.3)
Treatment - Week 52	Number Analyzed	58 participants	44 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 33.3)
Treatment - Week 56	Number Analyzed	61 participants	48 participants
		0.0; (0.0 to 33.3)	0.0; (0.0 to 33.3)
Treatment - Week 60	Number Analyzed	47 participants	39 participants
		0.0; (0.0 to 33.3)	0.0; (0.0 to 66.7)
Treatment - Week 64	Number Analyzed	55 participants	39 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 66.7)
Treatment - Week 68	Number Analyzed	49 participants	34 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 66.7)
Treatment - Week 72	Number Analyzed	54 participants	34 participants
		0.0; (0.0 to 33.3)	0.0; (0.0 to 33.3)
Treatment - Week 76	Number Analyzed	42 participants	29 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 33.3)
Treatment - Week 80	Number Analyzed	43 participants	23 participants
		0.0; (0.0 to 33.3)	0.0; (0.0 to 33.3)
Treatment - Week 84	Number Analyzed	33 participants	19 participants
		0.0; (0.0 to 33.3)	0.0; (0.0 to 33.3)
Treatment - Week 88	Number Analyzed	36 participants	16 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 66.7)
Treatment - Week 92	Number Analyzed	30 participants	13 participants
		0.0; (0.0 to 33.3)	0.0; (0.0 to 33.3)
Treatment - Week 96	Number Analyzed	22 participants	11 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 33.3)
Treatment - Week 100	Number Analyzed	18 participants	10 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 33.3)
Treatment - Week 104	Number Analyzed	15 participants	7 participants
		33.33; (0.0 to 66.7)	0.0; (0.0 to 33.3)
Treatment - Week 108	Number Analyzed	11 participants	7 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 33.3)
Treatment - Week 112	Number Analyzed	9 participants	4 participants
		0.0; (0.0 to 66.7)	16.67; (0.0 to 33.3)
Treatment - Week 116	Number Analyzed	4 participants	2 participants
		0.0; (0.0 to 33.3)	16.67; (0.0 to 33.3)
Treatment - Week 120	Number Analyzed	3 participants	0 participants
		0.0; (0.0 to 66.7)

28. Secondary Outcome

Title	HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title		Alectinib	Crizotinib
Arm/Group Description:		Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received crizotinib at 250 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
Overall Number of Participants Analyzed		152	151
Median (Full Range); Unit of Measure: Score on a scale
Baseline	Number Analyzed	100 participants	96 participants
		0.0; (0.0 to 100.0)	0.0; (0.0 to 100.0)
Treatment - Week 4	Number Analyzed	95 participants	89 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 100.0)
Treatment - Week 8	Number Analyzed	89 participants	84 participants
		0.0; (0.0 to 100.0)	0.0; (0.0 to 66.7)
Treatment - Week 12	Number Analyzed	75 participants	78 participants
		0.0; (0.0 to 100.0)	0.0; (0.0 to 66.7)
Treatment - Week 16	Number Analyzed	79 participants	73 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 66.7)
Treatment - Week 20	Number Analyzed	73 participants	67 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 66.7)
Treatment - Week 24	Number Analyzed	77 participants	71 participants
		0.0; (0.0 to 33.3)	0.0; (0.0 to 66.7)
Treatment - Week 28	Number Analyzed	67 participants	62 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 66.7)
Treatment - Week 32	Number Analyzed	73 participants	65 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 100.0)
Treatment - Week 36	Number Analyzed	64 participants	61 participants
		0.0; (0.0 to 100.0)	0.0; (0.0 to 66.7)
Treatment - Week 40	Number Analyzed	74 participants	50 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 100.0)
Treatment - Week 44	Number Analyzed	62 participants	47 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 100.0)
Treatment - Week 48	Number Analyzed	67 participants	47 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 66.7)
Treatment - Week 52	Number Analyzed	58 participants	44 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 66.7)
Treatment - Week 56	Number Analyzed	61 participants	48 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 66.7)
Treatment - Week 60	Number Analyzed	47 participants	39 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 66.7)
Treatment - Week 64	Number Analyzed	55 participants	39 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 66.7)
Treatment - Week 68	Number Analyzed	49 participants	34 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 66.7)
Treatment - Week 72	Number Analyzed	54 participants	34 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 66.7)
Treatment - Week 76	Number Analyzed	42 participants	29 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 33.3)
Treatment - Week 80	Number Analyzed	43 participants	23 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 33.3)
Treatment - Week 84	Number Analyzed	33 participants	19 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 33.3)
Treatment - Week 88	Number Analyzed	36 participants	16 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 66.7)
Treatment - Week 92	Number Analyzed	30 participants	13 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 100.0)
Treatment - Week 96	Number Analyzed	22 participants	11 participants
		33.33; (0.0 to 66.7)	0.0; (0.0 to 33.3)
Treatment - Week 100	Number Analyzed	18 participants	10 participants
		33.33; (0.0 to 66.7)	0.0; (0.0 to 66.7)
Treatment - Week 104	Number Analyzed	15 participants	7 participants
		33.33; (0.0 to 66.7)	0.0; (0.0 to 33.3)
Treatment - Week 108	Number Analyzed	11 participants	7 participants
		0.0; (0.0 to 66.7)	0.0; (0.0 to 33.3)
Treatment - Week 112	Number Analyzed	9 participants	4 participants
		0.0; (0.0 to 66.7)	16.67; (0.0 to 33.33)
Treatment - Week 116	Number Analyzed	4 participants	2 participants
		16.67; (0.0 to 33.33)	16.67; (0.0 to 33.33)
Treatment - Week 120	Number Analyzed	3 participants	0 participants
		33.33; (33.33 to 33.33)

Adverse Events

Time Frame	Baseline up to 43 months
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Alectinib	Crizotinib
Arm/Group Description	Participants received alectinib at 600 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.	Participants received crizotinib at 250 mg orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
All-Cause Mortality
	Alectinib	Crizotinib
	Affected / at Risk (%)	Affected / at Risk (%)
Total	35/152 (23.03%)	40/151 (26.49%)
Serious Adverse Events
	Alectinib	Crizotinib
	Affected / at Risk (%)	Affected / at Risk (%)
Total	44/152 (28.95%)	45/151 (29.80%)
Blood and lymphatic system disorders
Anaemia * 1	2/152 (1.32%)	0/151 (0.00%)
Cardiac disorders
Acute Myocardial Infarction * 1	0/152 (0.00%)	1/151 (0.66%)
Atrial Fibrillation * 1	0/152 (0.00%)	1/151 (0.66%)
Cardiac Arrest * 1	1/152 (0.66%)	1/151 (0.66%)
Myocardial Infarction * 1	0/152 (0.00%)	1/151 (0.66%)
Sinus Bradycardia * 1	0/152 (0.00%)	1/151 (0.66%)
Cardiac Tamponade * 1	1/152 (0.66%)	0/151 (0.00%)
Pericardial Effusion * 1	1/152 (0.66%)	0/151 (0.00%)
Eye disorders
Vision Blurred * 1	0/152 (0.00%)	1/151 (0.66%)
Gastrointestinal disorders
Nausea * 1	0/152 (0.00%)	3/151 (1.99%)
Vomiting * 1	0/152 (0.00%)	2/151 (1.32%)
Gastrointestinal Disorder * 1	0/152 (0.00%)	1/151 (0.66%)
Ileus * 1	0/152 (0.00%)	1/151 (0.66%)
Oesophagitis * 1	0/152 (0.00%)	1/151 (0.66%)
General disorders
Pyrexia * 1	1/152 (0.66%)	3/151 (1.99%)
Asthenia * 1	0/152 (0.00%)	1/151 (0.66%)
Chest Discomfort * 1	0/152 (0.00%)	1/151 (0.66%)
Hyperthermia Malignant * 1	0/152 (0.00%)	1/151 (0.66%)
Multiple Organ Dysfunction Syndrome * 1	0/152 (0.00%)	1/151 (0.66%)
Sudden Death * 1	0/152 (0.00%)	1/151 (0.66%)
Chest Pain * 1	1/152 (0.66%)	0/151 (0.00%)
Death * 1	1/152 (0.66%)	0/151 (0.00%)
Oedema * 1	1/152 (0.66%)	0/151 (0.00%)
Oedema Peripheral * 1	0/152 (0.00%)	1/151 (0.66%)
Hepatobiliary disorders
Cholelithiasis * 1	0/152 (0.00%)	1/151 (0.66%)
Drug-Induced Liver Injury * 1	1/152 (0.66%)	1/151 (0.66%)
Hepatic Haematoma * 1	0/152 (0.00%)	1/151 (0.66%)
Hepatic Haemorrhage * 1	1/152 (0.66%)	0/151 (0.00%)
Hepatotoxicity * 1	1/152 (0.66%)	0/151 (0.00%)
Cholecystitis Acute * 1	1/152 (0.66%)	0/151 (0.00%)
Infections and infestations
Pneumonia * 1	5/152 (3.29%)	4/151 (2.65%)
Lung Infection * 1	3/152 (1.97%)	0/151 (0.00%)
Bronchitis * 1	2/152 (1.32%)	0/151 (0.00%)
Urinary Tract Infection * 1	2/152 (1.32%)	0/151 (0.00%)
Bacteraemia * 1	1/152 (0.66%)	0/151 (0.00%)
Cellulitis * 1	1/152 (0.66%)	0/151 (0.00%)
Herpes Zoster * 1	1/152 (0.66%)	0/151 (0.00%)
Infection * 1	1/152 (0.66%)	0/151 (0.00%)
Influenza * 1	1/152 (0.66%)	0/151 (0.00%)
Sepsis * 1	1/152 (0.66%)	1/151 (0.66%)
Skin Infection * 1	1/152 (0.66%)	0/151 (0.00%)
Upper Respiratory Tract Infection * 1	1/152 (0.66%)	0/151 (0.00%)
Acinetobacter Infection * 1	0/152 (0.00%)	1/151 (0.66%)
Appendicitis * 1	0/152 (0.00%)	1/151 (0.66%)
Necrotising Fasciitis * 1	0/152 (0.00%)	1/151 (0.66%)
Oesophageal Candidiasis * 1	0/152 (0.00%)	1/151 (0.66%)
Pneumonia Klebsiella * 1	0/152 (0.00%)	1/151 (0.66%)
Injury, poisoning and procedural complications
Forearm Fracture * 1	0/152 (0.00%)	1/151 (0.66%)
Thoracic Vertebral Fracture * 1	1/152 (0.66%)	0/151 (0.00%)
Investigations
Blood Creatinine Increased * 1	2/152 (1.32%)	0/151 (0.00%)
Alanine Aminotransferase Increased * 1	1/152 (0.66%)	4/151 (2.65%)
Aspartate Aminotransferase Increased * 1	1/152 (0.66%)	1/151 (0.66%)
Human Chorionic Gonadotropin Increased * 1	1/152 (0.66%)	0/151 (0.00%)
Metabolism and nutrition disorders
Hyponatraemia * 1	1/152 (0.66%)	1/151 (0.66%)
Musculoskeletal and connective tissue disorders
Arthralgia * 1	0/152 (0.00%)	1/151 (0.66%)
Back Pain * 1	1/152 (0.66%)	0/151 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian Cancer * 1	0/152 (0.00%)	1/151 (0.66%)
Nervous system disorders
Aphasia * 1	0/152 (0.00%)	1/151 (0.66%)
Cerebral Haemorrhage * 1	0/152 (0.00%)	1/151 (0.66%)
Dizziness * 1	1/152 (0.66%)	1/151 (0.66%)
Epilepsy * 1	0/152 (0.00%)	1/151 (0.66%)
Hemiparesis * 1	0/152 (0.00%)	1/151 (0.66%)
Seizure * 1	0/152 (0.00%)	1/151 (0.66%)
Haemorrhage Intracranial * 1	1/152 (0.66%)	0/151 (0.00%)
Hypoglycaemic Coma * 1	1/152 (0.66%)	0/151 (0.00%)
Psychiatric disorders
Confusional State * 1	1/152 (0.66%)	2/151 (1.32%)
Disorientation * 1	1/152 (0.66%)	0/151 (0.00%)
Renal and urinary disorders
Renal Impairment * 1	0/152 (0.00%)	1/151 (0.66%)
Acute Kidney Injury * 1	4/152 (2.63%)	0/151 (0.00%)
Urinary Retention * 1	1/152 (0.66%)	0/151 (0.00%)
Reproductive system and breast disorders
Uterine Polyp * 1	1/152 (0.66%)	0/151 (0.00%)
Respiratory, thoracic and mediastinal disorders
Pneumonitis * 1	2/152 (1.32%)	4/151 (2.65%)
Pneumothorax * 1	2/152 (1.32%)	0/151 (0.00%)
Dyspnoea * 1	2/152 (1.32%)	1/151 (0.66%)
Pulmonary Embolism * 1	2/152 (1.32%)	3/151 (1.99%)
Bronchopleural Fistula * 1	1/152 (0.66%)	0/151 (0.00%)
Haemoptysis * 1	1/152 (0.66%)	1/151 (0.66%)
Pleural Effusion * 1	1/152 (0.66%)	1/151 (0.66%)
Pulmonary Haemorrhage * 1	1/152 (0.66%)	0/151 (0.00%)
Respiratory Failure * 1	1/152 (0.66%)	1/151 (0.66%)
Interstitial Lung Disease * 1	0/152 (0.00%)	1/151 (0.66%)
Skin and subcutaneous tissue disorders
Rash * 1	1/152 (0.66%)	0/151 (0.00%)
Vascular disorders
Deep Vein Thrombosis * 1	0/152 (0.00%)	2/151 (1.32%)
Lymphoedema * 1	0/152 (0.00%)	1/151 (0.66%)
Orthostatic Hypotension * 1	0/152 (0.00%)	1/151 (0.66%)
Thrombosis * 1	0/152 (0.00%)	1/151 (0.66%)
1 Term from vocabulary, MedDRA Version 19.1; * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Alectinib	Crizotinib
	Affected / at Risk (%)	Affected / at Risk (%)
Total	136/152 (89.47%)	140/151 (92.72%)
Blood and lymphatic system disorders
Anaemia * 1	29/152 (19.08%)	7/151 (4.64%)
Neutropenia * 1	4/152 (2.63%)	11/151 (7.28%)
Cardiac disorders
Bradycardia * 1	8/152 (5.26%)	14/151 (9.27%)
Sinus Bradycardia * 1	8/152 (5.26%)	7/151 (4.64%)
Eye disorders
Visual Impairment * 1	2/152 (1.32%)	18/151 (11.92%)
Vision Blurred * 1	3/152 (1.97%)	10/151 (6.62%)
Photopsia * 1	0/152 (0.00%)	9/151 (5.96%)
Gastrointestinal disorders
Constipation * 1	52/152 (34.21%)	49/151 (32.45%)
Nausea * 1	21/152 (13.82%)	70/151 (46.36%)
Diarrohea * 1	18/152 (11.84%)	68/151 (45.03%)
Vomiting * 1	11/152 (7.24%)	57/151 (37.75%)
Abdominal Pain * 1	9/152 (5.92%)	7/151 (4.64%)
Dyspepsia * 1	5/152 (3.29%)	12/151 (7.95%)
Abdominal Pain Upper * 1	8/152 (5.26%)	6/151 (3.97%)
Dysphagia * 1	1/152 (0.66%)	8/151 (5.30%)
General disorders
Oedema Peripheral * 1	26/152 (17.11%)	41/151 (27.15%)
Fatigue * 1	29/152 (19.08%)	25/151 (16.56%)
Asthenia * 1	11/152 (7.24%)	11/151 (7.28%)
Pyrexia * 1	7/152 (4.61%)	9/151 (5.96%)
Chest Pain * 1	9/152 (5.92%)	5/151 (3.31%)
Infections and infestations
Upper Respiratory Tract Infection * 1	13/152 (8.55%)	13/151 (8.61%)
Urinary Tract Infection * 1	10/152 (6.58%)	7/151 (4.64%)
Investigations
Alanine Aminotransferase Increased * 1	22/152 (14.47%)	42/151 (27.81%)
Aspartate Aminotransferase Increased * 1	20/152 (13.16%)	37/151 (24.50%)
Blood Bilirubin Increased * 1	23/152 (15.13%)	2/151 (1.32%)
Blood Creatinine Increased * 1	11/152 (7.24%)	6/151 (3.97%)
Blood Creatine Phosphokinase Increased * 1	8/152 (5.26%)	7/151 (4.64%)
Weight Increased * 1	15/152 (9.87%)	0/151 (0.00%)
Blood Alkaline Phosphatase Increased * 1	6/152 (3.95%)	8/151 (5.30%)
Gamma-Glutamyltransferase Increased * 1	1/152 (0.66%)	10/151 (6.62%)
Metabolism and nutrition disorders
Decreased Appetite * 1	14/152 (9.21%)	14/151 (9.27%)
Musculoskeletal and connective tissue disorders
Arthralgia * 1	17/152 (11.18%)	10/151 (6.62%)
Myalgia * 1	24/152 (15.79%)	3/151 (1.99%)
Back Pain * 1	12/152 (7.89%)	7/151 (4.64%)
Pain In Extremity * 1	6/152 (3.95%)	10/151 (6.62%)
Musculoskeletal Pain * 1	11/152 (7.24%)	3/151 (1.99%)
Nervous system disorders
Dysgeusia * 1	4/152 (2.63%)	29/151 (19.21%)
Dizziness * 1	12/152 (7.89%)	20/151 (13.25%)
Headache * 1	11/152 (7.24%)	13/151 (8.61%)
Paraesthesia * 1	3/152 (1.97%)	8/151 (5.30%)
Psychiatric disorders
Insomnia * 1	15/152 (9.87%)	9/151 (5.96%)
Respiratory, thoracic and mediastinal disorders
Cough * 1	11/152 (7.24%)	9/151 (5.96%)
Dyspnoea * 1	8/152 (5.26%)	6/151 (3.97%)
Productive Cough * 1	8/152 (5.26%)	1/151 (0.66%)
Skin and subcutaneous tissue disorders
Rash * 1	16/152 (10.53%)	14/151 (9.27%)
Alopecia * 1	1/152 (0.66%)	11/151 (7.28%)
Photosensitivity Reaction * 1	8/152 (5.26%)	0/151 (0.00%)
1 Term from vocabulary, MedDRA Version 19.1; * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: Medical Communications
• Organization: Hoffmann-La Roche
• Phone: 800-821-8590
• EMail: genentech@druginfo.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Dziadziuszko R, Peters S, Mok T, Camidge DR, Gadgeel SM, Ou SI, Konopa K, Noe J, Nowicka M, Bordogna W, Morcos PN, Smoljanovic V, Shaw AT. Circulating Cell-free DNA as a Prognostic Biomarker in Patients with Advanced ALK+ Non-small Cell Lung Cancer in the Global Phase III ALEX Trial. Clin Cancer Res. 2022 May 2;28(9):1800-1808. doi: 10.1158/1078-0432.CCR-21-2840.

Mok T, Camidge DR, Gadgeel SM, Rosell R, Dziadziuszko R, Kim DW, Perol M, Ou SI, Ahn JS, Shaw AT, Bordogna W, Smoljanovic V, Hilton M, Ruf T, Noe J, Peters S. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Ann Oncol. 2020 Aug;31(8):1056-1064. doi: 10.1016/j.annonc.2020.04.478. Epub 2020 May 11.

Gadgeel S, Peters S, Mok T, Shaw AT, Kim DW, Ou SI, Perol M, Wrona A, Novello S, Rosell R, Zeaiter A, Liu T, Nuesch E, Balas B, Camidge DR. Alectinib versus crizotinib in treatment-naive anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer: CNS efficacy results from the ALEX study. Ann Oncol. 2018 Nov 1;29(11):2214-2222. doi: 10.1093/annonc/mdy405.

Burudpakdee C, Wong W, Seetasith A, Corvino FA, Yeh W, Gubens M. Economic impact of preventing brain metastases with alectinib in ALK-positive non-small cell lung cancer. Lung Cancer. 2018 May;119:103-111. doi: 10.1016/j.lungcan.2018.03.008. Epub 2018 Mar 9.

Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS, Kim DW, Ou SI, Perol M, Dziadziuszko R, Rosell R, Zeaiter A, Mitry E, Golding S, Balas B, Noe J, Morcos PN, Mok T; ALEX Trial Investigators. Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Aug 31;377(9):829-838. doi: 10.1056/NEJMoa1704795. Epub 2017 Jun 6.

Gainor JF, Shaw AT. J-ALEX: alectinib versus crizotinib in ALK-positive lung cancer. Lancet. 2017 Jul 1;390(10089):3-4. doi: 10.1016/S0140-6736(17)31074-7. Epub 2017 May 10. No abstract available.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT02075840
• Other Study ID Numbers: BO28984; 2013-004133-33 ( EudraCT Number )
• First Submitted: February 27, 2014
• First Posted: March 3, 2014
• Results First Submitted: February 6, 2018
• Results First Posted: March 15, 2018
• Last Update Posted: May 14, 2024