443P - Phase III trial of afatinib vs erlotinib in patients (pts) with squamous cell carcinoma (SCC) of the lung (LUX-Lung 8): EGFR molecular aberrations...

Date 20 December 2015
Event ESMO Asia 2015 Congress
Session Poster presentation 2
Topics Anticancer Agents
Non-Small Cell Lung Cancer
Biological Therapy
Presenter Keunchil Park
Citation Annals of Oncology (2015) 26 (suppl_9): 125-147. 10.1093/annonc/mdv532
Authors K. Park1, W. Li2, C. Zhou3, E. Felip4, M. Cobo5, G.D. Goss6, J. Soria7, K. Syrigos8, N. Krämer9, V.K. Chand10, F. Solca11, S. Lu12
  • 1Samsung Medical Center, Sungkyunkwan University School of Medicine, 135-710 - Seoul/KR
  • 2Department Of Hematology & Oncology, First Hospital Affiliated to Jilin University, Jilin/CN
  • 3Department Of Medical Oncology, Tongji University Medical School Cancer Institute, Shanghai/CN
  • 4Department Of Oncology, Vall d’Hebron University Hospital, Barcelona/ES
  • 5Department Of Oncology, Hospital Carlos Haya, Malaga/ES
  • 6Division Of Medical Oncology, University of Ottawa, Ottawa/CA
  • 7Drug Development Department, Gustave Roussy Cancer Campus and University Paris-Sud, Paris/FR
  • 83rd Department Of Medicine, Athens School of Medicine, Athens/GR
  • 9Staburo Gmbh, Munich, Germany, on behalf of Boehringer Ingelheim Pharma GmBH & Co. KG, Biberach/DE
  • 10Medicine Ta Oncology, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield/US
  • 11Pharmacology And Translational Research, Boehringer Ingelheim GmbH, Vienna/AT
  • 12Shanghai Chest Hospital, affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai/CN



Aberrant expression of ErbB receptors and multiple defects in their signaling pathways are implicated in the pathobiology of SCC of the lung, providing rationale for ErbB inhibitors in this setting of major unmet medical need. Primary analysis of LUX-Lung 8 (LL8; 2nd-line afatinib [A], an irreversible ErbB family blocker vs erlotinib [E], a reversible EGFR tyrosine kinase inhibitor in pts with SCC of the lung) showed significantly better progression-free survival (PFS) with A. Here we report overall survival (OS), updated PFS and exploratory molecular analysis of tumor samples.


Pts with stage IIIB/IV disease were randomized 1:1 to A (40 mg/day) or E (150 mg/day) until progression. Primary endpoint: PFS; key secondary endpoint: OS; other endpoints: objective response (ORR), disease control (DCR), safety. Archived tumor samples from selected pts – with PFS >2 mos (presumed treatment benefit; n = 144) and a control group with PFS ≤2 mos (treatment refractory; n = 94) – were retrospectively analyzed using the FoundationOne™ next-generation sequencing (NGS) platform.


OS was significantly better with A (n = 398) vs E (n = 397); median 7.9 vs 6.8 mos, HR 0.81 [95% CI, 0.69–0.95], p = 0.008. PFS (median 2.6 vs 1.9 mos, HR 0.81 [95% CI, 0.69–0.96], p = 0.010); ORR (5.5 vs 2.8%; p = 0.055) and DCR (50.5 vs 39.5%; p = 0.002) were better for A vs E. Prespecified subgroup analyses for PFS and OS favored A. Grade ≥3 adverse events were similar with A and E (57.1 vs 57.5%). Preliminary NGS results (A: 130; E: 108 samples) focused on genomic alterations of EGFR. Only 14 EGFR short variants (A: 8; E: 6; 10 novel with unknown clinical significance) were detected. EGFR gene amplification frequency was also low (A: 9; E: 6). No correlation of EGFR aberrations with PFS/OS was observed. NGS analyses are ongoing.


OS was significantly improved with A vs E in pts with SCC of the lung in a 2nd-line setting. PFS and DCR were also significantly better. The improvements were not driven by the presence of EGFR short variants or amplifications and may relate to afatinib's ability to inactivate multiple ErbB signaling cascades. Based on LL8, A should be preferred over E in these pts.

Clinical trial identification

EudraCT No.: 2011-002380-24


K. Park: employment by Samsung Medical Center, and uncompensated advisory board participation for Boehringer Ingelheim. E. Felip: advisory board participation for Eli Lilly, Pfizer, Roche, Boehringer Ingelheim and MSD; and honoraria for lectures from AstraZeneca, Bristol-Myers Squibb and Novartis. G.D. Goss: advisory board participation for AstraZeneca, Boehringer Ingelheim and Bristol-Myers Squibb. J.-C. Soria: advisory board participation for Bayer, Bristol-Meyers Squibb, Sanofi, Roche and BiB. N. Krämer: consultant to Boehringer Ingelheim Pharma GmBH & Co. KG, Biberach, Germany and receives compensation for these services. V.K. Chand, F. Solca: employment by Boehringer Ingelheim. All other authors have declared no conflicts of interest.