140PD - LUX-Lung 7: A Phase IIb, global, randomised, open-label trial of afatinib vs gefitinib as first-line treatment for patients (pts) with advanced non...

Date 14 April 2016
Event European Lung Cancer Conference 2016 (ELCC) 2016
Session Targeting EGFR and ALK driven tumours
Topics Cytotoxic agents
Non-small-cell lung cancer
Therapy
Biological therapy
Presenter Keunchil Park
Citation Journal of Thoracic Oncology (2016) 11 (supplement 4): S57-S166. S1556-0864(16)X0004-4
Authors K. Park1, E. Tan2, L. Zhang3, V. Hirsh4, K. O'Byrne5, M. Boyer6, J.C. Yang7, T.S.K. Mok8, M. Kim9, L. Paz-Ares10
  • 1Samsung Medical Center, Sungkyunkwan University School of Medicine, 135-710 - Seoul/KR
  • 2Division Of Medicial Oncology, National Cancer Center, Singapore/SG
  • 3Cancer Center, Sun Yat-Sen University, Guangzhou/CN
  • 4Department Of Oncology, McGill University, Montreal/CA
  • 5Translational Research Institute, Princess Alexandra Hospital and Queensland University of Technology, Brisbane/AU
  • 6Department Of Medical Oncology, Chris O'Brien Lifehouse, Camperdown/AU
  • 7Department Of Oncology, National Taiwan University Hospital and National Taiwan University, Taipei/TW
  • 8Key Laboratory Of South China, Department Of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong/CN
  • 9Medicine Ta Oncology, Boehringer Ingelheim GmbH, Ingelheim/DE
  • 10Hospital Universitario Doce De Octubre, and CNIO, Madrid/ES

Abstract

Background

Afatinib is an irreversible ErbB family blocker approved for first-line treatment of advanced EGFR-mutant (m+) NSCLC. This global, randomised, open-label, Phase IIb trial prospectively compared the efficacy and safety of afatinib to the reversible EGFR tyrosine kinase inhibitor gefitinib for first-line treatment of pts with EGFRm+ NSCLC.

Methods

Pts with stage IIIB/IV EGFRm+ NSCLC were randomised (1:1) to afatinib or gefitinib, stratified by mutation type (Del19 or L858R) and brain metastases (presence/absence). There were 3 co-primary endpoints: progression free survival (PFS) by independent review, time to treatment failure (TTF) and overall survival (OS). Secondary endpoints included objective response rate (ORR), disease control rate, tumour shrinkage and safety.

Results

Pts received daily afatinib (40 mg; n = 160) or gefitinib (250 mg; n = 159) until radiological disease progression or beyond if deemed beneficial by investigator. Baseline characteristics were balanced in treatment arms (Asian: 58.8% vs 55.3%, EGFR Del19: 57.5% vs 58.5%), respectively, with slightly more females in the gefitinib arm (56.9% vs 66.7%). PFS was significantly improved with afatinib vs gefitinib (HR = 0.73; 95% CI, 0.57–0.95; p = 0.017), as was TTF (HR = 0.73; 95% CI, 0.58–0.92; p = 0.007). Consistent treatment benefit was seen across the subgroups including mutation type and race. Independently assessed ORR was significantly higher with afatinib vs gefitinib (70% vs 56%, p = 0.008). OS data are not mature. Common grade ≥3 related adverse events (AEs) were: diarrhoea (12.5%) and rash/acne (9.4%) with afatinib, and alanine aminotransferase increase (8.2%) with gefitinib. There was no drug-related interstitial lung disease for afatinib (vs 4 gefitinib pts; 2.5%). Discontinuation due to drug-related AEs was the same in each arm (6.3%).

Conclusions

Afatinib significantly improved PFS compared with gefitinib as first-line treatment of EGFRm+ pts. Afatinib treatment benefit was also seen for TTF and ORR. The AE profiles for both drugs were manageable and discontinuation due to AEs was equally low.

Clinical trial identification

NCT01466660

Legal entity responsible for the study

Boehringer Ingelheim

Funding

Boehringer Ingelheim

Disclosure

K. Park: Advisory board participation for AstraZeneca, Boehringer Ingelheim, Clovis, Eli Lilly, Hanmi, Novartis, Ono and Roche. E.-H. Tan: Advisory board participation for, and honoraria from, Boehringer Ingelheim and Novartis. L. Zhang: Advisory board participation for Boehringer Ingelheim and AstraZeneca. V. Hirsh: Honoraria from Boehringer Ingelheim. K. O'Byrne: Consultation fees from Pfizer, Roche, AZD, Boehringer Ingelheim, BMS, MSD, Lilly Oncology and Novartis; honoraria for speaker's bureaus from Pfizer, Roche, AZD, Lilly Oncology, Boehringer Ingelheim; owner of stock in CARP Pharmaceuticals and Bluesky Biosciences; organiser of the annual Brisbane Cancer Conference hosted by the Princess Alexandra Hospital Research Foundation which raises money from sponsors including AZD, Roche, MSD, BMS, Astellas, Boehringer Ingelheim, Celgene, Ipsen, Janssen, Lilly Oncology, Merck, Novartis, Pfizer, Takeda, Illumina and Thermofisher. M. Boyer: MB reports advisory board participation for Pfizer, AstraZeneca and Merck; corporate-sponsored research for Boehringer Ingelheim, Pfizer, AstraZeneca, Roche/Genentech and Merck; and honoraria from Boehringer Ingelheim, Pfizer and AstraZeneca. J. Yang: Advisory board participation for, and honoraria from, Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genentech, AstraZeneca, Astellas, Bayer, MSD, Merck Serono, Pfizer, Novartis, Clovis Oncology and Celgene. T. Mok: Stock or other ownership from Sanomics LTD.; honoraria from AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, BI, Merck Serono, MSD, Janssen, Clovis Oncology, BioMarin, GSK, Amgen, Novartis, SFJ Pharmaceutical, ACEA Biosciences, Vertex Pharmaceuticals, BMS, AVEO & Biodesix, Prime Oncology; advisory board participation for AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, BI, Merck Serono, MSD, Janssen, Clovis Oncology, BioMarin, GSK, Novartis, SFJ Pharmaceutical, ACEA Biosciences, Vertex Pharmaceuticals, AVEO & Biodesix, BMS, geneDecode Co., Ltd.; speakers bureau for AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, BI, MSD, Amgen, Janssen, Clovis Oncology, GSK, Novartis, BMS, Prime Oncology. M. Kim: MK reports full-time employment by Boehringer Ingelheim. L. Paz-Ares: Advisory board participation from Lilly, BMS, Pfizer, Roche, MSD, Clovis and Boehringer Ingelheim.