BIBW 2992 (Afatinib) Versus Chemotherapy as First Line Treatment in NSCLC With EGFR Mutation
A Randomised, Open-label, Phase III Study of BIBW 2992 Versus Chemotherapy as First-line Treatment for Patients With Stage IIIB or IV Adenocarcinoma of the Lung Harbouring an EGFR Activating Mutation
2 other identifiers
interventional
345
24 countries
124
Brief Summary
This randomised, open label phase III trial will be performed in patients with adenocarcinoma of the lung with tumours harbouring an Epidermal Growth Factor Receptor activating mutation. The objectives of the trial are to compare the efficacy of single agent BIBW 2992, Arm A, with Pemetrexed/Cisplatin chemotherapy, Arm B, as first line treatment for this group of patients.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Aug 2009
Longer than P75 for phase_3
124 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 29, 2009
CompletedFirst Posted
Study publicly available on registry
July 30, 2009
CompletedStudy Start
First participant enrolled
August 14, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 9, 2012
CompletedResults Posted
Study results publicly available
November 19, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
March 16, 2017
CompletedApril 6, 2018
March 1, 2018
2.5 years
July 29, 2009
August 8, 2013
March 9, 2018
Conditions
Outcome Measures
Primary Outcomes (1)
Progression-Free Survival (PFS) Time
PFS was defined as time from randomisation to disease progression or death whichever occured first. Assessed by central independent review according to the Response Evaluation Criteria in Solid Tumours (RECIST 1.1). Median time results from unstratified Kaplan-Meier estimates.
Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
Secondary Outcomes (12)
Percentage of Patients With Objective Response (OR)
Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
Percentage of Participants With Disease Control (DC)
Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
Overall Survival (OS) Time
From randomisation to cut-off date (17MAR2017).
Tumour Shrinkage
Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
Change From Baseline in Body Weight
Baseline and throughout the trial until progression (every 3 weeks), up to 28 months.
- +7 more secondary outcomes
Study Arms (2)
BIBW 2992
EXPERIMENTALBIBW 2992 tablet once daily until progression
Cisplatin/Pemetrexed
ACTIVE COMPARATORCisplatin and Pemetrexed IV once every 3 weeks for up to 6 cycles
Interventions
Eligibility Criteria
You may qualify if:
- Pathologically confirmed diagnosis of Stage IIIB (with cytologically proven pleural effusion or pericardial effusion) or Stage IV adenocarcinoma of the lung. Patients with mixed histology are eligible if adenocarcinoma is the predominant histology.
- Epidermal Growth Factor Receptor mutation detected by central laboratory analysis of tumour biopsy material.
- Measurable disease according to RECIST 1.1.
- Eastern Cooperative Oncology Group score of 0 or 1.
- Age \>/= 18 years.
- Life expectancy of at least three months.
- Written informed consent that is consistent with International Conference on Harmonisation-Good Clinical Practice guidelines.
You may not qualify if:
- Prior chemotherapy for relapsed and/or metastatic NSCLC. Neoadjuvant/adjuvant chemotherapy is permitted if at least 12 months has elapsed between the end of chemotherapy and randomisation.
- Prior treatment with Epidermal Growth Factor Receptor targeting small molecules or antibodies.
- Radiotherapy or surgery (other than biopsy) within 4 weeks prior to randomisation.
- Active brain metastases
- Any other current malignancy or malignancy diagnosed within the past five years
- Known pre-existing interstitial lung disease.
- Significant or recent acute gastrointestinal disorders with diarrhoea as a major symptom.
- History or presence of clinically relevant cardiovascular abnormalities.
- Any other concomitant serious illness or organ system dysfunction.
- Adequate absolute neutrophil count and platelet count
- Adequate liver and kidney function
- Active hepatitis B infection, active hepatitis C infection or known HIV carrier.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (133)
Highlands Oncology Group
Fayetteville, Arkansas, 72703, United States
Clinical Trials and Research Associates Inc
Montebello, California, 90640, United States
Innovative Medical Research of South Florida
Miami, Florida, 33179, United States
Crescent City Research Consortiom
Marrero, Louisiana, 70072, United States
Interlakes Foundation, Incorporated
Rochester, New York, 14623, United States
Lehigh Valley Hospital / Lehigh Valley Health Network
Allentown, Pennsylvania, 18103, United States
South Texas Institute of Cancer, Northwest Cancer Center
Corpus Christi, Texas, 78410, United States
Instituto de Medicina Nuclear de Bahía Blanca
Bahía Blanca, B8000FJI, Argentina
Hospital Alemán
Capital Federal, C1118AAT, Argentina
Imcaba S.R.L.
Capital Federal, C1185AAT, Argentina
IMAI Research
Capital Federal, C1425AWC, Argentina
Instituto Alexander Fleming
Capital Federal, C1426ANZ, Argentina
Hospital Militar Central
Capital Federal, C1426BOR, Argentina
PALIAR
Capital Federal, C1430ERF, Argentina
Centro Oncológico de Rosario
Rosario, S2000KZE, Argentina
Lifehouse
Camperdown, New South Wales, 2050, Australia
Royal North Shore Hospital
St Leonards, New South Wales, 2065, Australia
Calvary Mater Newcastle Hospital
Waratah, New South Wales, 2298, Australia
The Prince Charles Hospital
Chermside, Queensland, 4032, Australia
Flinders Medical Centre
Bedford Park, South Australia, 5042, Australia
The Burnside War Memorial Hospital
Toorak Gardens, South Australia, 5065, Australia
Box Hill Hospital
Box Hill, Victoria, 3128, Australia
St. Vincents Hospital (MEL)
Fitzroy, Victoria, 3065, Australia
Mount Medical Centre
Perth, Western Australia, 6000, Australia
KH d. Elisabethinen Linz
Linz, 4010, Austria
SMZ Baumgartner Hoehe Otto Wagner Spital
Vienna, 1140, Austria
Klinikum Wels - Grieskirchen GmbH
Wels, 4600, Austria
Brussels - UNIV St-Pierre
Brussels, 1000, Belgium
UNIV UZ Gent
Ghent, 9000, Belgium
Brussels - UNIV UZ Brussel
Jette, 1090, Belgium
UZ Leuven
Leuven, 3000, Belgium
Centre Hospitalier Universitaire de Liège
Liège, 4000, Belgium
Centro de Pesquisa do Hospital Lifecenter
Belo Horizonte, Brazil
Centro de Pesquisas Clínicas em Oncología
Cachoeiro de Itapemirim, 29308-014, Brazil
Insituto de Oncologia do Paraná
Curitiba, 80530-010, Brazil
Hospital São Lucas da Pontifícia Universidade Católica
Porto Alegre, 90610-000, Brazil
UNIFESP Departamento de Medicina de Pneumologia
São Paulo, 04023-900, Brazil
Tom Baker Cancer Centre
Calgary, Alberta, T2N 4N2, Canada
Cross Cancer Institute (University of Alberta)
Edmonton, Alberta, T6G 1Z2, Canada
Charles LeMoyne Hospital
Greenfield Park, Migration Data, J4V 2H1, Canada
Hematologiste et oncologue medical CHUM - Hopital Notre-Dame
Montreal, Migration Data, H2L 4M1, Canada
McGill University, Department of Oncology
Montreal, Migration Data, H2W 1S6, Canada
Hospital Dirección de Previsión de Carabineros
Los Condes, 760-0746, Chile
Instituto Oncológico Limitada Viña del Mar
Reñaca, 2540364, Chile
Instituto Clínico Oncológico del Sur - ICOS
Temuco, Chile
HOP d'Angers
Angers, 49933, France
HOP Côte de Nacre
Caen, 14033, France
HOP Nord Michallon
La Tronche, 38700, France
HOP Croix Rousse, Pneumo, Lyon
Lyon, 69317, France
INS Curie
Paris, 75248, France
HOP Sud-Réunion, Pneumo, Saint Pierre
Saint Pierre - La Réunion, 97448, France
CTR René Gauducheau
Saint-Herblain, 44805, France
HOP - HIA Sainte Anne
Toulon, 83041, France
HOP, Pneumo, Villefranche sur Saône
Villefranche-sur-Saône, 69655, France
Universitätsklinikum Benjamin Franklin, Berlin
Berlin, 12200, Germany
Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH
Essen, 45122, Germany
Medizinische Hochschule Hannover
Hanover, 30625, Germany
Lungenklinik Hemer
Hemer, 58675, Germany
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Mainz, 55101, Germany
Universitätsklinikum Münster
Münster, 48149, Germany
Pius-Hospital, Oldenburg
Oldenburg, 26121, Germany
National Taiwan University Hospital
Taipei, 100, Germany
Queen Mary Hospital
Hong Kong, Hong Kong
Prince of Wales Hospital
Shatin, Hong Kong
Szent György Hospital, Szekesfehervar
Székesfehérvár, 8000, Hungary
Markusovszky County Hospital, Szombathely
Szombathely, 9700, Hungary
Zala County Hospital, Zalaegerszeg
Zalaegerszeg, 8900, Hungary
St James's Hospital
Dublin, Ireland
Ospedale San Donato di Arezzo
Arezzo, 52100, Italy
Az. USL 4 di Prato
Prato, 59100, Italy
Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza
Roma, 00189, Italy
Osp. Silvestrin
Sant'Andrea Delle Fratte (PG), 06132, Italy
National Hospital Organization Nagoya Medical Center
Aichi, Nagoya, 460-0001, Japan
Aichi Cancer Center Hospital
Aichi, Nagoya, 464-8681, Japan
National Cancer Center Hospital East
Chiba, Kashiwa, 277-8577, Japan
National Hospital Organization Shikoku Cancer Center
Ehime, Matsuyama, 791-0280, Japan
National Hospital Organization Kyushu Cancer Center
Fukuoka, Fukuoka, 811-1395, Japan
Hokkaido University Hospital
Hokkaido, Sapporo, 060-8648, Japan
Institute of Biomedical Research and Innovation Hospital
Hyogo, Kobe, 650-0047, Japan
Kanazawa University Hospital
Ishikawa, Kanazawa, 920-8641, Japan
Kanagawa Cardiovascular and Respiratory Center
Kanagawa, Yokohama, 236-0051, Japan
Niigata Cancer Center Hospital
Niigata, Niigata, 951-8566, Japan
Kurashiki Central Hospital
Okayama, Kurashiki, 710-8602, Japan
Okayama University Hospital
Okayama, Okayama, 700-8558, Japan
Kindai University Hospital
Osaka, Osaka-Sayama, 589-8511, Japan
Osaka City Hospital Organization Osaka City General Hospital
Osaka, Osaka, 534-0021, Japan
National Hospital Organization Kinki-Chuo Chest Medical Center
Sakai, Osaka, 591-8555, Japan
Shizuoka Cancer Center
Shizuoka, Sunto-gun, 411-8777, Japan
Hospital Pulau Pinang
Palau Pinang, 10990, Malaysia
Pusat Perubatan University Kebangsaan Malaysia
Wilayah Persekutuan, 5600, Malaysia
University Malaya Medical Centre
Wilayah Persekutuan, 59100, Malaysia
Hospital Nacional Guillermo Almenara Irigoyen
La Victoria, Peru
Clínica Anglo Americana
San Isidro, 27, Peru
Instituto Nacional de Enfermedades Neoplásicas
Surquillo, 34, Peru
Perpetual Succour Hospital (Cebu)
Cebu City, 6000, Philippines
Makati Medical Center
Makati City, 1229, Philippines
St. Luke Medical Centre
Quezon, 1102, Philippines
Institutul Oncologic "Prof. Dr. Ion Chiricuta"
Cluj-Napoca, 400015, Romania
ONCOLAB SRL, Craiova
Craiova, 200535, Romania
Republic Clinical Oncology Dispensary, Dept. Chemotherapy
Kazan', 420029, Russia
FSBSI "N.N Blokhin Medical Research Center of Oncology"
Moscow, 115478, Russia
Medical Radiology Science Centre
Obninsk, 249020, Russia
First Pavlov State Medical University Saint Petersburg
Saint Petersburg, 197022, Russia
SPb SBIH "City Clinical Oncological Dispensary"
Saint Petersburg, 197022, Russia
FSBI "N.N. Petrov National Medical Research Center of Oncology" of MoH of RF
Saint Petersburg, 197758, Russia
Chungbuk National University Hospital
Cheongju-si, 361-771, South Korea
Chonnam National University Hwasun Hospital
Hwasun, 519-763, South Korea
Seoul National University Bundang Hospital
Seongnam, 13620, South Korea
Asan Medical Center
Seoul, 138-736, South Korea
Ulsan University Hospital
Ulsan, 682-714, South Korea
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, 807, Taiwan
Chang Gung Memorial Hospital Kaohsiung
Kaohsiung City, 833, Taiwan
China Medical University Hospital
Taichung, 40447, Taiwan
Taichung Veterans General Hospital
Taichung, 40705, Taiwan
NCKUH
Tainan, 704, Taiwan
Taipe Veterans General Hospital
Taipei, 112, Taiwan
Tri-Service General Hospital
Taipei, 114, Taiwan
Chang Gung Memorial Hospital(TaoYuan)
Taoyuan District, 33305, Taiwan
Ramathibodi Hospital
Bangkok, 10400, Thailand
Maharaj Nakorn Chiang Mai Hospital
Chiang Mai, 50200, Thailand
Srinagarind Hospital
Khonkaen, 40002, Thailand
Songklanagarind Hospital
Songkhla, 90110, Thailand
City Clinical Hospital #4, Dnipropetrovsk State Medical Academy
Dnipropetrovsk, 49102, Ukraine
Donetsk Regional Antitumor Centre
Donetsk, 83000, Ukraine
Kharkiv Regional Clinical Oncology Center
Kharkiv, 16070, Ukraine
Lviv State Oncological Regional Treatment & Diagnostic CTR
Lviv, 79031, Ukraine
Royal Devon and Exeter Hospital
Exeter, EX2 5DW, United Kingdom
Royal Surrey County Hospital
Guildford, GU2 7XX, United Kingdom
The Royal Marsden Hospital
London, SW3 6JJ, United Kingdom
Maidstone Hospital, Kent Oncology Centre
Maidstone, ME16 9QQ, United Kingdom
Scunthorpe General Hospital, Oncology
Scunthorpe, DN15 7BH, United Kingdom
The Royal Marsden Hospital
Sutton, SM2 5PT, United Kingdom
Royal Cornwall Hospital
Truro, TR1 3LJ, United Kingdom
Related Publications (9)
Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma With EGFR Mutations. J Clin Oncol. 2023 Jun 1;41(16):2869-2876. doi: 10.1200/JCO.22.02547.
PMID: 37235976DERIVEDWu YL, Sequist LV, Tan EH, Geater SL, Orlov S, Zhang L, Lee KH, Tsai CM, Kato T, Barrios CH, Schuler M, Hirsh V, Yamamoto N, O'Byrne K, Boyer M, Mok T, Peil B, Marten A, Chih-Hsin Yang J, Paz-Ares L, Park K. Afatinib as First-line Treatment of Older Patients With EGFR Mutation-Positive Non-Small-Cell Lung Cancer: Subgroup Analyses of the LUX-Lung 3, LUX-Lung 6, and LUX-Lung 7 Trials. Clin Lung Cancer. 2018 Jul;19(4):e465-e479. doi: 10.1016/j.cllc.2018.03.009. Epub 2018 Mar 17.
PMID: 29653820DERIVEDYang JC, Sequist LV, Zhou C, Schuler M, Geater SL, Mok T, Hu CP, Yamamoto N, Feng J, O'Byrne K, Lu S, Hirsh V, Huang Y, Sebastian M, Okamoto I, Dickgreber N, Shah R, Marten A, Massey D, Wind S, Wu YL. Effect of dose adjustment on the safety and efficacy of afatinib for EGFR mutation-positive lung adenocarcinoma: post hoc analyses of the randomized LUX-Lung 3 and 6 trials. Ann Oncol. 2016 Nov;27(11):2103-2110. doi: 10.1093/annonc/mdw322. Epub 2016 Sep 6.
PMID: 27601237DERIVEDSchuler M, Wu YL, Hirsh V, O'Byrne K, Yamamoto N, Mok T, Popat S, Sequist LV, Massey D, Zazulina V, Yang JC. First-Line Afatinib versus Chemotherapy in Patients with Non-Small Cell Lung Cancer and Common Epidermal Growth Factor Receptor Gene Mutations and Brain Metastases. J Thorac Oncol. 2016 Mar;11(3):380-90. doi: 10.1016/j.jtho.2015.11.014. Epub 2016 Jan 25.
PMID: 26823294DERIVEDKato T, Yoshioka H, Okamoto I, Yokoyama A, Hida T, Seto T, Kiura K, Massey D, Seki Y, Yamamoto N. Afatinib versus cisplatin plus pemetrexed in Japanese patients with advanced non-small cell lung cancer harboring activating EGFR mutations: Subgroup analysis of LUX-Lung 3. Cancer Sci. 2015 Sep;106(9):1202-11. doi: 10.1111/cas.12723. Epub 2015 Jul 25.
PMID: 26094656DERIVEDYang JC, Sequist LV, Geater SL, Tsai CM, Mok TS, Schuler M, Yamamoto N, Yu CJ, Ou SH, Zhou C, Massey D, Zazulina V, Wu YL. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015 Jul;16(7):830-8. doi: 10.1016/S1470-2045(15)00026-1. Epub 2015 Jun 4.
PMID: 26051236DERIVEDYang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O'Byrne K, Feng J, Lu S, Huang Y, Geater SL, Lee KY, Tsai CM, Gorbunova V, Hirsh V, Bennouna J, Orlov S, Mok T, Boyer M, Su WC, Lee KH, Kato T, Massey D, Shahidi M, Zazulina V, Sequist LV. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015 Feb;16(2):141-51. doi: 10.1016/S1470-2045(14)71173-8. Epub 2015 Jan 12.
PMID: 25589191DERIVEDYang JC, Hirsh V, Schuler M, Yamamoto N, O'Byrne KJ, Mok TS, Zazulina V, Shahidi M, Lungershausen J, Massey D, Palmer M, Sequist LV. Symptom control and quality of life in LUX-Lung 3: a phase III study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3342-50. doi: 10.1200/JCO.2012.46.1764. Epub 2013 Jul 1.
PMID: 23816967DERIVEDSequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3327-34. doi: 10.1200/JCO.2012.44.2806. Epub 2013 Jul 1.
PMID: 23816960DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Boehringer Ingelheim Call Center
- Organization
- Boehringer Ingelheim
Study Officials
- STUDY CHAIR
Boehringer Ingelheim
Boehringer Ingelheim
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 29, 2009
First Posted
July 30, 2009
Study Start
August 14, 2009
Primary Completion
February 9, 2012
Study Completion
March 16, 2017
Last Updated
April 6, 2018
Results First Posted
November 19, 2013
Record last verified: 2018-03