440O - Afatinib (A) vs gefitinib (G) in patients (pts) with EGFR mutation-positive (EGFRm+) NSCLC: overall survival (OS) data from LUX-Lung 7 (LL7)

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Thoracic cancers
Topics Anti-Cancer Agents & Biologic Therapy
Biomarkers
Non-Small-Cell Lung Cancer, Metastatic
Presenter James Chih-Hsin Yang
Citation Annals of Oncology (2016) 27 (suppl_9): ix139-ix156. 10.1093/annonc/mdw594
Authors K. Park1, E.H. Tan2, L. Zhang3, V. Hirsh4, K. O'Byrne5, M. Boyer6, J.C. Yang7, T. Mok8, K.H. Lee9, S. Lu10, Y. Shi11, S. Kim12, J. Laskin13, D. Kim14, S.A. Laurie15, K. Kölbeck16, J. Fan17, N. Dodd18, A. Märten19, L.G. Paz-Ares20
  • 1Medical Oncology, Samsung Medical Center Sungkyunkwan University School of Medicine, 135-710 - Seoul/KR
  • 2Division Of Medicial Oncology, National Cancer Center, Singapore/SG
  • 3State Key Laboratory Of Oncology In South China, Collaborative Innovation Center For Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou/CN
  • 4Department Of Oncology, McGill University, Montreal/CA
  • 5Cancer Section, 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
  • 8Department Of Clinical Oncology, Key Laboratory of South China, The Chinese University of Hong Kong, Hong Kong/CN
  • 9Medical Oncolgy, Chungbuk National University Hospital, Cheong-ju/KR
  • 10Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai/CN
  • 11Department Of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing/CN
  • 12Department Of Oncology, Asan Medical Center, Seoul/KR
  • 13Medical Oncology, BC Cancer Agency, Vancouver/CA
  • 14Department Of Internal Medicine, Seoul National University Hospital, Seoul/KR
  • 15Division Of Medical Oncology, The Ottawa Hospital Cancer Centre, Ottawa/CA
  • 16Pulmonary Diseases, Karolinska University Hospital-Solna, Stockholm/SE
  • 17Clinical Pharmacology, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield/US
  • 18Biostatistics, Boehringer Ingelheim Ltd UK, Bracknell/GB
  • 19Ta Oncology, Boehringer Ingelheim GmbH, Ingelheim am Rhein/DE
  • 20Medical Oncology, Hospital Universitario Doce de Octubre and CNIO, Madrid/ES

Abstract

Background

The irreversible ErbB family blocker, A, and the reversible EGFR TKI, G, are approved for 1st-line treatment (tx) of advanced EGFRm+ NSCLC. In the Phase IIb LL7 trial, A (40 mg/d) significantly improved PFS (HR 0.73 [95% CI 0.57–0.95], p = 0.017), ORR (70 vs 56%, p = 0.008) and time to tx failure (TTF; HR 0.73 [0.58–0.92], p = 0.007) vs G (250 mg/d) in this setting. Here, we present primary analysis of OS.

Methods

LL7 assessed A vs G in tx-naïve pts with stage IIIb/IV NSCLC and a common EGFR mutation (Del19/L858R). Co-primary endpoints were PFS, TTF and OS; other endpoints included ORR and AEs. Primary OS analysis was planned after ∼213 OS events and follow-up of ≥ 32 mos.

Results

At data cut-off (8 Apr 2016), median follow-up for OS was 42.6 mos. Median tx duration was 13.7 (A) vs 11.5 (G) mos. 73%/77% (A/G) of pts who discontinued A/G had ≥1 subsequent systemic anticancer tx. 46%/56% (A/G) received a subsequent EGFR TKI; 20 (14%)/23 (15%) pts (A/G) received a 3rd-generation EGFR TKI. There was a trend towards improved OS with A vs G (median 27.9 vs 24.5 mos; HR 0.86 [0.66–1.12], p = 0.258). Landmark 24-mo and 30-mo OS (A vs G) was 61% vs 51% and 48% vs 40%. Similar OS trends were seen with A vs G in pts with Del19 (30.7 vs 26.4 mos; HR 0.83 [0.58–1.17]) and L858R (25.0 vs 21.2 mos; HR 0.92 [0.62–1.36]) mutations. There was a trend towards improved OS with A vs G in pts who received a 3rd-generation EGFR TKI (NE vs 46.0 mos; HR 0.51 [0.17–1.52]). Consistent OS outcomes were observed across age groups in the A arm (median, mos: 27.9 [≥60 yrs]; 26.7 [≥65 yrs]; 25.1 [≥70 yrs]; 27.9 [≥75 yrs]). 74/62 (46%/39%; A/G) pts survived for >30 mos; of patients who received A, >30-mo survival rates were generally similar across countries of origin and mean average dose received. Similar to the primary analyses, updated PFS, TTF and ORR data were significantly improved with A vs G. The AE profile of A and G was virtually unchanged since the primary analysis.

Conclusions

In LL7, there was a trend towards improved OS with A vs G that was generally consistent across subgroups. Updated PFS (independent review), TTF and ORR all significantly favored A over G.

Clinical trial indentification

ClinTrials.gov:NCT01466660/EudraCT:2011-001814-33 (release date: 2011-12-29)

Legal entity responsible for the study

N/A

Funding

Boehringer Ingelheim

Disclosure

K. Park: Advisory board: BI; Corporate-sponsored research: AZ. L. Zhang: Advisory board: AstraZeneca, BMS; Corporate-sponsored research: BMS, Pfizer, Lilly; Honoraria: AZ, Roche, Lilly. V. Hirsh: Advisory board: AstraZeneca, Roche, Pfizer, Merck, Boehringer Ingelheim, Amgen, Lilly; Honoraria: AstraZeneca, Roche, Pfizer, Merck, Boehringer Ingelheim, Amgen, Lilly. K. O\'Byrne: Honoraria: Pfizer, Roche, AZD, BI, BMS, MSD, Lilly Oncology, Novartis; Consultancy/Advisory: Pfizer, Roche, AZD, Lilly Oncology, MSD, BI; Travel expenses: Roche, AZD, BI, MSD; Stock: CARP Pharmaceuticals; TCD Ref L002-310-01, US patent 13/601,703 entitled “Global Analysis of Serum mircoRNAs as Potential Biomarkers for Lung Adenocarcinoma [filed 31.08.12); Australian Provisional Patent Number 2015905380 entitled “Nucleic Acid Oligomers and Uses therof. M. Boyer: Advisory board: Merck, Bristol Myers, Pfizer Corporate-sponsored research: Merck, Bristol Myers, Boehringer Ingelheim, Amgen, Clovis, Astra Zeneca, Eli Lilly, Novartis. J.C-H. Yang: Advisory board (and honoraria TBC): Boehringer Ingelheim, Eli Lilly, Bayer, Roche/Genentech/Chugai, Astrazeneca, Astellas, MSD, Merck Serono, Pfizer, Novartis, Clovis Oncology, Celgene, Innopharma, Merrimack. T. Mok: Stock ownership: Sanomics Ltd; Advisory board: AZ, Roche/Genentech, Pfizer, Eli Lilly, BI, Merck Serono, MSD, Janssen, Clovis Oncology, BioMarin, GSK, Novartis, SFJ Pharmaceutical, ACEA Biosciences, Inc., Vertex Pharmaceuticals, Aveo & Biodesix, BMS, geneDecode Co., Ltd., OncoGenex Technologies Inc.; Board of directors: IASLC, Chinese Lung Cancer Research Foundation Ltd., Chinese Society of Clinical Oncology (CSCO), Hong Kong Cancer Therapy Society (HKCTS); Corporate-sponsored research: AZ, BI, Pfizer, Novartis, SFJ, Roche, MSD, Clovis Oncology, BMS. J. Fan, N. Dodd, A. Märten: Employment: Boehringer Ingelheim. L. Paz-Ares: Honoraria: Pfizer, Boehringer Ing, Lilly, Roche, BMS, MSD, Novartis, Amgen. All other authors have declared no conflicts of interest.