Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): A phase 2b/3 randomised trial

Vincent A. Miller, Vera Hirsh, Jacques Cadranel, Yuh Min Chen, Keunchil Park, Sang We Kim, Caicun Zhou, Wu Chou Su, Mengzhao Wang, Yan Sun, Dae Seog Heo, Lucio Crino, Eng Huat Tan, Tsu Yi Chao, Mehdi Shahidi, Xiuyu Julie Cong, Robert M. Lorence, James Chih Hsin Yang

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Abstract

Background: Afatinib, an irreversible ErbB-family blocker, has shown preclinical activity when tested in EGFR mutant models with mutations that confer resistance to EGFR tyrosine-kinase inhibitors. We aimed to assess its efficacy in patients with advanced lung adenocarcinoma with previous treatment failure on EGFR tyrosine-kinase inhibitors. Methods: In this phase 2b/3 trial, we enrolled patients with stage IIIB or IV adenocarcinoma and an Eastern Cooperative Oncology Group performance (ECOG) performance score of 0-2 who had received one or two previous chemotherapy regimens and had disease progression after at least 12 weeks of treatment with erlotinib or gefitinib. We used a computer-generated sequence to randomly allocate patients (2:1) to either afatinib (50 mg per day) or placebo; all patients received best supportive care. Randomisation was done in blocks of three and was stratified by sex and baseline ECOG performance status (0-1 vs 2). Investigators, patients, and the trial sponsor were masked to treatment assignment. The primary endpoint was overall survival (from date of randomisation to death), analysed on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT00656136. Findings: Between May 26, 2008, and Sept 21, 2009, we identified 697 patients, 585 of whom were randomly allocated to treatment (390 to afatinib, 195 to placebo). Median overall survival was 10·8 months (95% CI 10·0-12·0) in the afatinib group and 12·0 months (10·2-14·3) in the placebo group (hazard ratio 1·08, 95% CI 0·86-1·35; p=0·74). Median progression-free survival was longer in the afatinib group (3·3 months, 95% CI 2·79-4·40) than it was in the placebo group (1·1 months, 0·95-1·68; hazard ratio 0·38, 95% CI 0·31-0·48; p

Original languageEnglish
Pages (from-to)528-538
Number of pages11
JournalThe Lancet Oncology
Volume13
Issue number5
DOIs
Publication statusPublished - May 2012

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Non-Small Cell Lung Carcinoma
Placebos
Drug Therapy
Lung
Random Allocation
Protein-Tyrosine Kinases
Survival
Treatment Failure
Disease-Free Survival
Disease Progression
gefitinib
Erlotinib Hydrochloride
BIBW 2992
Adenocarcinoma
Therapeutics
Research Personnel
Mutation

ASJC Scopus subject areas

  • Oncology

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Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1) : A phase 2b/3 randomised trial. / Miller, Vincent A.; Hirsh, Vera; Cadranel, Jacques; Chen, Yuh Min; Park, Keunchil; Kim, Sang We; Zhou, Caicun; Su, Wu Chou; Wang, Mengzhao; Sun, Yan; Heo, Dae Seog; Crino, Lucio; Tan, Eng Huat; Chao, Tsu Yi; Shahidi, Mehdi; Cong, Xiuyu Julie; Lorence, Robert M.; Yang, James Chih Hsin.

In: The Lancet Oncology, Vol. 13, No. 5, 05.2012, p. 528-538.

Research output: Contribution to journalArticle

Miller, VA, Hirsh, V, Cadranel, J, Chen, YM, Park, K, Kim, SW, Zhou, C, Su, WC, Wang, M, Sun, Y, Heo, DS, Crino, L, Tan, EH, Chao, TY, Shahidi, M, Cong, XJ, Lorence, RM & Yang, JCH 2012, 'Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): A phase 2b/3 randomised trial', The Lancet Oncology, vol. 13, no. 5, pp. 528-538. https://doi.org/10.1016/S1470-2045(12)70087-6
Miller, Vincent A. ; Hirsh, Vera ; Cadranel, Jacques ; Chen, Yuh Min ; Park, Keunchil ; Kim, Sang We ; Zhou, Caicun ; Su, Wu Chou ; Wang, Mengzhao ; Sun, Yan ; Heo, Dae Seog ; Crino, Lucio ; Tan, Eng Huat ; Chao, Tsu Yi ; Shahidi, Mehdi ; Cong, Xiuyu Julie ; Lorence, Robert M. ; Yang, James Chih Hsin. / Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1) : A phase 2b/3 randomised trial. In: The Lancet Oncology. 2012 ; Vol. 13, No. 5. pp. 528-538.
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AU - Miller, Vincent A.

AU - Hirsh, Vera

AU - Cadranel, Jacques

AU - Chen, Yuh Min

AU - Park, Keunchil

AU - Kim, Sang We

AU - Zhou, Caicun

AU - Su, Wu Chou

AU - Wang, Mengzhao

AU - Sun, Yan

AU - Heo, Dae Seog

AU - Crino, Lucio

AU - Tan, Eng Huat

AU - Chao, Tsu Yi

AU - Shahidi, Mehdi

AU - Cong, Xiuyu Julie

AU - Lorence, Robert M.

AU - Yang, James Chih Hsin

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