102P - LUX-Lung 8 phase III trial: Analysis of long-term response to second-line afatinib in patients with advanced squamous cell carcinoma (SCC) of the lung

Date 07 May 2017
Event ELCC 2017
Session Poster Display Session
Topics Cancer Immunology and Immunotherapy
Lung and other Thoracic Tumours
Presenter James Chih-Hsin Yang
Citation Annals of Oncology (2017) 28 (suppl_2): ii28-ii51. 10.1093/annonc/mdx091
Authors J.C. Yang1, G. Goss2, E. Felip3, S. Lu4, A. Ardizzoni5, S.M. Gadgeel6, V. Georgoulias7, N. Dupuis8, E. Ehrnrooth9, J. Soria10
  • 1National Taiwan University Hospital and National Taiwan University Cancer Center, 100 - Taipei/TW
  • 2University of Ottawa, Ottawa/CA
  • 3Vall d’ Hebron University Hospital, Barcelona/ES
  • 4Shanghai Chest Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai/CN
  • 5University Hospital, Bologna/IT
  • 6Karmanos Cancer Institute/Wayne State University, Detroit/US
  • 7University Hospital of Heraklion, Heraklion, Crete/GR
  • 8Biodesix Inc., Boulder/US
  • 9Boehringer Ingelheim, Danmark A/S/DK
  • 10Department Of Medicine, Gustave Roussy Cancer Campus and University Paris-Sud, Paris/FR

Abstract

Background

In LUX-Lung 8, afatinib (A; 40mg/day) significantly improved OS (median 7.9 vs 6.8 months, p = 0.008) and PFS (2.6 vs 1.9 months, p = 0.010) versus erlotinib (E; 150mg/day) in pts with pretreated SCC of the lung (n = 795). 12-month (36 vs 28%; p = 0.016) and 18-month survival (22 vs 14%; p = 0.013) were significantly higher with A than E, indicating that some pts derive prolonged benefit from A. This is a post-hoc analysis of baseline characteristics and efficacy/safety of A in long-term responders (LTRs; treatment for ≥12 months). Archived tumor samples and serum were analyzed to identify potential biomarkers.

Methods

Tumor samples were retrospectively analyzed using next-generation sequencing (NGS); EGFR expression was determined by IHC. Pre-treatment serum samples were analyzed with VeriStrat® and classified as VeriStrat-Good or VeriStrat-Poor.

Results

21/398 pts treated with A were LTRs. Six pts were still on treatment at the time of data cut-off. The median duration of treatment was 17.6 months (range: 12.3–27.6). Baseline characteristics were similar to the overall dataset (median age: 64 y [range: 54–81]; male: 76%; Asian: 29%; ECOG 0/1: 33%/67%; best response to chemotherapy CR or PR/SD: 48%/52%; current and ex-smokers: 90%). Median PFS was 16.6 months (range: 2.8–25.8); median OS was 21.1 months (12.9–31.6). The most common treatment-related AEs (all grade/grade 3) were: diarrhea (81%/5%); rash/acne (71%/5%); stomatitis (29%/5%). AEs generally occurred soon after treatment onset. Six pts had dose reductions due to related AEs. NGS data in ten LTRs will be presented. Genomic aberrations in the ErbB gene family were identified in 50% of these pts (overall dataset: 26.5%). Of 17 pts assessed by VeriStrat, 88% were VeriStrat-Good (overall dataset: 62%). IHC data were available for only one LTR (EGFR-).

Conclusions

Baseline characteristics of LTRs to A were similar to the overall dataset. A conferred median OS of almost 2 years in this subgroup. A was well tolerated with predictable, transient AEs. Though biomarker data look promising, the cohort was too small to identify any clear NGS/VeriStrat predictive signals; further studies are required.

Clinical trial identification

LUX-Lung 8: EudraCT No: 2011-002380-24

Legal entity responsible for the study

Boehringer Ingelheim

Funding

Boehringer Ingelheim

Disclosure

J.C-H. Yang: Ad board and honoraria: BI, Lilly, Bayer, Roche/Genentech/Chugai, Astellas, MSD, Merck Serono, Pfizer, Novartis, Clovis, Celgene, Merrimack, Yuhan Pharmaceuticals, BMS, Ono pharmaceutical Daiichi, Sankyo, and AZ. G. Goss: Participated on advisory boards for AstraZeneca, Boehringer Ingelheim, Pfizer, Eli Lilly, Bristol-Myers Squibb, and Celgene. E. Felip: Participated on advisory boards for Eli Lilly, Pfizer, Roche, MSD, and Boehringer Ingelheim. Felip has receieved lecture fees from AstraZeneca, Bristol-Myers Squibb, and Novartis. A. Ardizzoni: Received honoraria and participated on advisory boards for Bristol-Myers Squibb, MSD, Eli-Lilly, and Boehringer Ingelheim. Ardizzoni has received honoraria from Pfizer and Bayer. S.M. Gadgeel: Participated on advisory boards for Boehringer Ingelheim, Pfizer, Genentech, ARIAD, AstraZeneca, Bristol-Myers Squibb, and Roche. N. Dupuis: Employee of and owns stock in Biodesix. E. Ehrnrooth: Employee of Boehringer Ingelheim. J-C. Soria: Astrazeneca, Astex, GSK, Gammamabs, Lilly, MSD, Merus, Pfizer, Pharmamar, Pierre Fabre, Roche, Sanofi, Servier, Symphogen, Takeda. All other authors have declared no conflicts of interest.