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

Non-Small Cell Lung Cancer Clinical Trial

— ALEX  

Official title:

Randomized, Multicenter, Phase III, Open-Label Study of Alectinib Versus Crizotinib in Treatment-Naive Anaplastic Lymphoma Kinase-Positive Advanced Non-Small Cell Lung Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02075840
• Other study ID #: BO28984
• Secondary ID: 2013-004133-33
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: August 19, 2014
• Est. completion date: September 29, 2026

Study information

• Verified date: May 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized, active controlled, multicenter phase III open-label study is designed to evaluate the efficacy and safety of alectinib compared with crizotinib treatment in participants with treatment-naive anaplastic lymphoma kinase-positive (ALK-positive) advanced non-small cell lung cancer (NSCLC). Participants will be randomized in a 1:1 ratio to receive either alectinib, 600 milligrams (mg) orally twice daily (BID), or crizotinib, 250 mg orally BID. Participants will receive treatment until disease progression, unacceptable toxicity, withdrawal of consent, or death. The study is expected to last approximately 144 months.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 303
• Est. completion date: September 29, 2026
• Est. primary completion date: February 9, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC that is ALK-positive as assessed by the Ventana immunohistochemistry (IHC) test

• Life expectancy of at least 12 weeks

• Eastern cooperative oncology group performance status (ECOG PS) of 0-2

• Participants with no prior systemic treatment for advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC

• Adequate renal, and hematologic function

• Participants must have recovered from effects of any major surgery or significant traumatic injury at least 28 days before the first dose of study treatment

• Measurable disease by response evaluation criteria in solid tumors (RECIST) version 1.1 (v1.1) prior to the administration of study treatment

• Prior brain or leptomeningeal metastases allowed if asymptomatic (e.g., diagnosed incidentally at study baseline)

• Negative pregnancy test for all females of child bearing potential

• Use of highly effective contraception as defined by the study protocol

Exclusion Criteria:

• Participants with a previous malignancy within the past 3 years

• Any gastrointestinal (GI) disorder or liver disease

• National cancer institute common terminology criteria for adverse events (NCI CTCAE) (version 4.0) Grade 3 or higher toxicities due to any prior therapy (e.g., radiotherapy) (excluding alopecia)

• History of organ transplant

• Co-administration of anti-cancer therapies other than those administered in this study

• Participants with baseline QTc greater than (>) 470 milliseconds or symptomatic bradycardia

• Recipient of strong/potent cytochrome P4503A inhibitors or inducers within 14 days prior to the first dose until the end of study treatment

• Recipient of any drug with potential QT interval prolonging effects within 14 days prior to the first dose for all participants and while on treatment through the end of the study for crizotinib-treated participants only

• History of hypersensitivity to any of the additives in the alectinib and crizotinib drug formulation

• Pregnancy or lactation

• Any clinically significant disease or condition (or history of) that could interfere with, or for which the treatment might interfere with, the conduct of the study or the absorption of oral medications or that would, in the opinion of the principal investigator, pose an unacceptable risk to the participant in this study

• Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol requirements and/or follow-up procedures; those conditions should be discussed with the participant before trial entry

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• Alectinib
Participants will receive alectinib 600 mg orally (four 150 mg capsules) BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.
• Crizotinib
Participants will receive crizotinib 250 mg capsules orally BID from Visit 0 (baseline) until disease progression, unacceptable toxicity, withdrawal of consent or death.

Locations

Country	Name	City	State
Australia	Kinghorn Cancer Centre; St Vincents Hospital	Darlinghurst	New South Wales
Australia	Royal North Shore Hospital; Oncology	St. Leonards	New South Wales
Australia	Monash Health Translational Precinct; Clinical Trials Centre, Level 3	Victoria
Australia	Calvary Mater Newcastle; Medical Oncology	Waratah	New South Wales
Australia	Queen Elizabeth Hospital; Medical Oncology	Woodville South	South Australia
Bosnia and Herzegovina	University Clinical Centre of the Republic of Srpska; Clinic for Pulmonary Diseases	Banja Luka
Bosnia and Herzegovina	University Clinical Center Sarajevo;Clinic for Pulmonary disease	Sarajevo
Bosnia and Herzegovina	University Clinical Center Sarajevo;Institute of oncology	Sarajevo
Brazil	Hospital das Clinicas - UFRGS	Porto Alegre	RS
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo	SP
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	Saskatoon Cancer Centre; Uni of Saskatoon Campus	Saskatoon	Saskatchewan
Canada	Mount Sinai Hospital; Oncology	Toronto	Ontario
Canada	Sunnybrook Odette Cancer Centre	Toronto	Ontario
Chile	Centro Internacional de Estudios Clínicos (CIEC)	Recoleta
China	Sun Yet-sen University Cancer Center	Guangzhou City
China	Shanghai Pulmonary Hospital	Shanghai
Costa Rica	Clinica CIMCA	San José
Egypt	Kasr Eieny Uni Hospital; Oncology (Nemrock)	Cairo
France	Chu Grenoble - Hopital Albert Michallon; Departement de Cancero-Hematologie	Grenoble
France	CHRU de Lille	Lille
France	Centre Leon Berard; Departement Oncologie Medicale	Lyon
France	Hopital Haut Leveque	Pessac
France	Hopital Pontchaillou	Rennes
Germany	St. Vincentius Kliniken Karlsruhe; Abteilung Hämatologie / Onkologie	Karlsruhe
Germany	Klinik Löwenstein gGmbH Medizinische Klinik II	Löwenstein
Guatemala	Grupo Angeles	Guatemala City
Hong Kong	Pamela Youde Nethersole Eastern Hospital; Clinical Oncology	Hong Kong
Hong Kong	Princess Margaret Hospital; Oncology	Hong Kong
Hong Kong	Queen Mary Hospital; Medicine & Respiratory	Hong Kong
Hong Kong	Tuen Mun Hospital; Clinical Oncology	Hong Kong
Hong Kong	Prince of Wales Hosp; Dept. Of Clinical Onc	Shatin
Israel	Rambam Medical Center; Oncology	Haifa
Israel	Meir Medical Center; Oncology	Kfar-Saba
Italy	Irccs Ist. Tumori Giovanni Paolo Ii; Dipartimento Oncologia Medica	Bari	Puglia
Italy	Az Ospedaliera Nuovo Garibaldi Quartiere Nesima; Oncologia Medica	Catania	Sicilia
Italy	Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica	Milano	Lombardia
Italy	Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1	Milano	Lombardia
Italy	Seconda Universita' Degli Studi; Divsione Di Oncologia Medica	Napoli	Campania
Italy	Az. Osp. S. Luigi Gonzaga; Malattie Apparato Respiratorio 5 Ad Indirizzo Oncologico	Orbassano	Piemonte
Italy	A.O. Universitaria Di Parma; Oncologia Medica	Parma	Emilia-Romagna
Italy	Ospedale Provinciale Santa Maria Delle Croci; Oncologia Medica	Ravenna	Emilia-Romagna
Italy	Policlinico Umberto i di Roma; dip. Scienze Radiologiche, Oncologiche, Anatomopatologiche	Roma	Lazio
Italy	Azienda Ospedaliera Di Perugia Ospedale s. Maria Della Misericordia; Oncologia Medica	Sant'Andrea Delle Fratte (PG)	Umbria
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Mexico	Instituto Nacional De Enfermedades Respiratorias;Unidad de Investigación	Ciudad de México	Mexico CITY (federal District)
New Zealand	Uni of Auckland; Medical School	Auckland
Poland	Uniwersyteckie Centrum Kliniczne; Klinika Onkologii i Radioterapii	Gdansk
Poland	Ms Clinsearch Specjalistyczny Niepubliczny Zaklad Opieki Zdrowotnej	Lublin
Poland	Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie; Oddzial onkologii z pododdzialem chemioterapii	Olsztyn
Poland	Mazowieckie Centrum Leczenia Chorob Pluc I Gruzlicy; Oddzial Iii	Otwock
Poland	Centrum Onkologii - Inst.Im. Marii Sklodowskiej-Curie; Oncology	Warszawa
Portugal	CHUC - Unidade de Pneumologia Oncológica; Hospital de Dia de Oncologia Edificio Sao Jeronimo	Coimbra
Portugal	IPO de Lisboa; Servico de Pneumologia	Lisboa
Portugal	IPO do Porto; Servico de Oncologia Medica	Porto
Russian Federation	Moscow City Oncology Hospital #62	Moscovskaya Oblast	Moskovskaja Oblast
Russian Federation	N.N.Burdenko Main Military Clinical Hospital; Oncology Dept	Moscow	Moskovskaja Oblast
Russian Federation	City Clinical Hospital No. 1	Novosibirsk
Russian Federation	Medical Radiological Research Centre Rams; Dept. of Radiotherapy & Chemotherapy of Hemoblastosis	Obninsk	Kaluga
Russian Federation	SPb City Clin Onc Dsp; Chemotherapy	Sankt-peterburg	Sankt Petersburg
Russian Federation	Scientific Research Oncology Institute named after N.N. Petrov; Oncology	St. Petersburg	Sankt Petersburg
Serbia	Clinical Center of Serbia	Belgrade
Serbia	Institute for pulmonary diseases of Vojvodina	Sremska Kamenica
Singapore	National Cancer Centre; Medical Oncology	Singapore
Singapore	National University Hospital; National University Cancer Institute, Singapore (NCIS)	Singapore
Spain	Hospital General Univ. de Alicante; Servicio de Oncologia	Alicante
Spain	Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia	Badalona	Barcelona
Spain	Hospital Universitario Quiron Dexeus	Barcelona
Spain	Hospital Universitario Puerta de Hierro; Servicio de Oncologia	Majadahonda	Madrid
Spain	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Sant Andreu de La Barca	Barcelona
Spain	Hospital Universitario Virgen del Rocio; Servicio de Oncologia	Sevilla
Switzerland	Universitaetsspital Basel; Onkologie	Basel
Switzerland	Inselspital Bern; Universitätsklinik für Medizinische Onkologie, Klinische Forschungseinheit	Bern
Switzerland	CHUV; Departement d'Oncologie	Lausanne
Switzerland	UniversitätsSpital Zürich; Zentrum für Hämatologie und Onkologie, Klinik für Onkologie	Zürich
Taiwan	National Cheng Kung Univ Hosp	Tainan
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei City
Taiwan	Taichung Veterans General Hospital	Xitun Dist.
Thailand	National Cancer Inst.	Bangkok
Thailand	Chiang Rai Prachanukroh Hospital; Department Of Medicine	Chiang Rai
Thailand	Khonkaen Hospital	Khonkaen
Thailand	King Chulalongkorn Memorial Hospital; Faculty of Medicine Chulalongkorn University	Patumwan
Thailand	Songklanagarind Hospital; Department of Internal Medicine, Division of Respiratory	Songkhla
Turkey	Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital; Medical Oncology	Adana
Turkey	Ankara University Medical Faculty; Medikal Onkoloji	Ankara
Turkey	Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department	Edirne
Turkey	Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department	Malatya
Ukraine	Dnipropetrovsk State Medical Academy; Chemotherapy Department	Dnipropetrovsk
Ukraine	Karkiv Regional Oncology Center	Kharkiv
Ukraine	Kyiv Regional Oncological Dispensary	Kyiv
Ukraine	Lviv State Oncology Regional Treatment and Diagnostic Centre; Department of hemotherapy	Lviv
United Kingdom	Birmingham Heartlands Hospital; Dept of Oncology	Birmingham
United Kingdom	Guys & St Thomas Hospital; Department of Oncology	London
United Kingdom	University College London Hospital	London
United States	Emory University Hospital	Atlanta	Georgia
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	Beth Israel Deaconess Med Ctr; Hem/Onc	Boston	Massachusetts
United States	Dana Farber Can Ins	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	University of Illinois at Chicago	Chicago	Illinois
United States	UT Southwestern Medical Center	Dallas	Texas
United States	University of Miami-Deerfield Beach	Deerfield Beach	Florida
United States	Henry Ford Health System	Detroit	Michigan
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	St. Mary's Hospital Regional Cancer Center	Grand Junction	Colorado
United States	University of Texas M.D. Anderson Cancer Center	Houston	Texas
United States	Comprehensive Cancer Center - Peak	Las Vegas	Nevada
United States	Northwest Georgia Oncology Centers, a Service of WellStar Cobb Hospital	Marietta	Georgia
United States	SCRI Oncology Partners	Nashville	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	North Valley Hem Onc Med Grp; Thomas&Dorothy Leavey Can Ctr	Northridge	California
United States	Chao Family Comprehensive Cancer Center; UC Irvine Medical Center	Orange	California
United States	Cancer Institute of Florida PA	Orlando	Florida
United States	Memorial Health Care System	Pembroke Pines	Florida
United States	Mayo Clinic Arizona	Phoenix	Arizona
United States	TMPN/ Cancer Care Associates	Redondo Beach	California
United States	Washington Uni School of Medicine	Saint Louis	Missouri
United States	UCSF Helen Diller Family CCC	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Bosnia and Herzegovina,  Brazil,  Canada,  Chile,  China,  Costa Rica,  Egypt,  France,  Germany,  Guatemala,  Hong Kong,  Israel,  Italy,  Korea, Republic of,  Mexico,  New Zealand,  Poland,  Portugal,  Russian Federation,  Serbia,  Singapore,  Spain,  Switzerland,  Taiwan,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS) by Investigator Assessment	PFS was assessed as time to disease progression or death whichever occurred first by investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) Criteria. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 millimeter (mm) and the appearance of new lesions.	Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Primary	Percentage of Participants With PFS Event by Investigator Assessment	PFS was assessed percentage of participants with disease progression or death whichever occurred first by investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) Criteria. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 millimeter (mm) and the appearance of new lesions.	Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Secondary	PFS Independent Review Committee (IRC)-Assessed	PFS was assessed as time to disease progression or death whichever occurred first by IRC assessment using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) Criteria. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm and the appearance of new lesions.	Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Secondary	Percentage of Participants With PFS Event by IRC	PFS was assessed as percentage of participants with disease progression or death whichever occurred first by IRC assessment using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) Criteria. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm and the appearance of new lesions.	Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Secondary	Percentage of Participants With Central Nervous System (CNS) Progression as Determined by IRC Using RECIST V1.1 Criteria	CNS progression was assessed as percentage of participants with an event defined as time from randomization until first radiographic evidence of CNS progression by IRC. The risk for a CNS progression without a prior non-CNS progression with alectinib compared with crizotinib.	Randomization to CNS PD as first occurrence of disease progression (assessed every 8 weeks up to 33 months)
Secondary	Percentage of Participants With Central Nervous System (CNS) Progression as Determined by IRC Using Revised Assessment in Neuro Oncology (RANO) Criteria	CNS progression was assessed as percentage of participants with event defined as time from randomization until first radiographic evidence of CNS progression by IRC. The risk for a CNS progression without a prior non-CNS progression with alectinib compared with crizotinib.	Randomization to the first occurrence of disease progression in the CNS (assessed every 8 weeks up to 33 months)
Secondary	Percentage of Participants With Objective Response Rate (ORR) of Complete Response (CR) or Partial Response (PR) as Determined by The Investigators According to RECIST V1.1 Criteria	ORR was defined as the percentage of participants who attained CR or PR. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.	Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Secondary	Duration of Response (DOR) According to RECIST V1.1 Criteria as Assessed by the Investigators	DOR was defined as the time from when response (CR or PR) was first documented to first documented disease progression or death, whichever occurred first. DOR was evaluated for participants who had a best overall response (BOR) of CR or PR.	First occurrence of objective response to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Secondary	Overall Survival (OS)	Overall survival (OS) was defined as the time from randomization to death from any cause.	From randomization until death (up to 43 months)
Secondary	Percentage of Participants With OS Event	Overall survival (OS) was defined as the time from randomization to death from any cause.	From randomization until death (up to 43 months)
Secondary	Percentage of Participants With CNS ORR of CR or PR IRC-assessed According to RECIST v1.1 Criteria	CNS ORR was defined as the percentage of participants who attained CR or PR and had measurable/non-measurable CNS lesions at baseline. As per RECIST v1.1, CR: Disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm, PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.	Randomization to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Secondary	CNS DOR IRC-assessed According to RECIST v1.1 Criteria	CNS DOR was defined as the time from when response (CR or PR) was first documented to first documented disease progression or death, whichever occurred first. DOR was evaluated for participants who had a best overall response (BOR) of CR or PR.	First occurrence of CNS objective response to first documented disease progression or death, whichever occurs first (assessed every 8 weeks up to 33 months)
Secondary	Percentage of Participants With Adverse Events	An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.	Baseline up to 28 months in the crizotinib arm and up to 30 months in the alectinib arm
Secondary	Area Under The Concentration-Time Curve (AUC) of Alectinib		Pre-dose (within 2 hours before alectinib) (baseline), 1, 2, 4, 6, and 8 hours post-dose at Visit 0 (first dosing day) and Week 4; Pre-dose (within 2 hours) at Week 8, then every 8 weeks until disease progression or death/withdrawal (up to 33 months)
Secondary	Maximum Concentration (Cmax) of Alectinib		Pre-dose (within 2 hours before alectinib), 1, 2, 4, 6, and 8 hours post-dose at baseline and Week 4; Pre-dose (within 2 hours before alectinib) at Week 8, then every 8 weeks until disease progression or death/withdrawal from study (up to 33 months)
Secondary	Time to Reach Cmax (Tmax) of Alectinib		Pre-dose (within 2 hours before alectinib), 1, 2, 4, 6, and 8 hours post-dose at baseline and Week 4; Pre-dose (within 2 hours before alectinib) at Week 8, then every 8 weeks until disease progression or death/withdrawal from study (up to 33 months)
Secondary	AUC of Alectinib Metabolite		Pre-dose (within 2 hours before alectinib) (baseline), 1, 2, 4, 6, and 8 hours post-dose at Visit 0 (first dosing day) and Week 4; Pre-dose (within 2 hours) at Week 8, then every 8 weeks until disease progression or death/withdrawal (up to 33 months)
Secondary	Cmax of Alectinib Metabolite		Pre-dose (within 2 hours before alectinib), 1, 2, 4, 6, and 8 hours post-dose at baseline and Week 4; Pre-dose (within 2 hours before alectinib) at Week 8, then every 8 weeks until disease progression or death/withdrawal from study (up to 33 months)
Secondary	Tmax of Alectinib Metabolite		Pre-dose (within 2 hours before alectinib), 1, 2, 4, 6, and 8 hours post-dose at baseline and Week 4; Pre-dose (within 2 hours before alectinib) at Week 8, then every 8 weeks until disease progression or death/withdrawal from study (up to 33 months)
Secondary	Time to Deterioration by European Organization for The Research And Treatment of Cancer (EORTC) Quality Of Life Questionnaire Core 30 (C30)	The EORTC QLQ-30 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning. Confirmed clinically meaningful deterioration in global health status or function is defined as a >or=10-point decrease from baseline in a symptom score that must be held for at least two consecutive assessments or an initial >or=10-point decrease from baseline followed by death within 5 weeks from the last assessment.	Baseline, every 4 weeks until disease progression (up to 33 months)
Secondary	Percentage of Participants With Deterioration by EORTC Quality Of Life Questionnaire Core 30 (C30)	The EORTC QLQ-30 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning. Confirmed clinically meaningful deterioration in global health status or function is defined as a >or=10-point decrease from baseline in a symptom score that must be held for at least two consecutive assessments or an initial >or=10-point decrease from baseline followed by death within 5 weeks from the last assessment.	Baseline, every 4 weeks until disease progression (up to 33 months)
Secondary	Time to Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13)	The EORTC QLQ-LC13 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning. Confirmed clinically meaningful deterioration in lung cancer symptoms is defined as a >or=10-point increase from baseline in a symptom score that must be held for at least two consecutive assessments or an initial >or=10-point increase above baseline followed by death within 5 weeks from the last assessment.	Baseline, every 4 weeks until disease progression (up to 33 months)
Secondary	Percentage of Participants With Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13)	The EORTC QLQ-LC13 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning. Confirmed clinically meaningful deterioration in lung cancer symptoms is defined as a >or=10-point increase from baseline in a symptom score that must be held for at least two consecutive assessments or an initial >or=10-point increase above baseline followed by death within 5 weeks from the last assessment.	Baseline, every 4 weeks until disease progression (up to 33 months)
Secondary	Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score	The EORTC QLQ-C30 questionnaire consisted of 30 questions generating five functional scores (physical, role, cognitive, emotional, and social); a global health status/global quality of life scale score; three symptom scale scores (fatigue, pain, and nausea and vomiting); and six stand alone one-item scores that capture additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and perceived financial burden. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning.	Baseline, every 4 weeks until disease progression (up to 33 months)
Secondary	HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing	The EORTC QLQ-LC13 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning.	Baseline, every 4 weeks until disease progression (up to 33 months)
Secondary	HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea	The EORTC QLQ-LC13 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning.	Baseline, every 4 weeks until disease progression (up to 33 months)
Secondary	HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest	The EORTC QLQ-LC13 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning.	Baseline, every 4 weeks until disease progression (up to 33 months)
Secondary	HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder	The EORTC QLQ-LC13 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All the scales and single-item scores were linearly transformed so that each score ranged from 0 to 100. A higher score on the global health and functioning subscales is indicative of better functioning.	Baseline, every 4 weeks until disease progression (up to 33 months)