509TiP - Lux-Lung 8: A Randomized, Open-Label, Phase III Trial of Afatinib vs. Erlotinib in Patients with Advanced Squamous Cell Carcinoma of the Lung as Second-Line Therapy Following First-Line Platinum-Based Chemotherapy

Abstract

ABSTRACT Background Patients with advanced squamous cell carcinoma (SCC) of the lung have limited treatment options. Although treatment with the EGFR tyrosine kinase inhibitor erlotinib is indicated in the second- or third-line or maintenance setting, the benefit is limited. Afatinib is a novel, selective, orally bioavailable, ErbB family blocker, irreversibly blocking EGFR (ErbB1), HER2 (ErbB2) and HER4 (ErbB4). Based on its promising preclinical profile and clinical activity in trials of SCC of the head and neck and lung, we seek to determine if the irreversible inhibition of the ErbB family translates into clinical benefit for patients with SCC of the lung. Methods This trial will compare the efficacy of afatinib versus erlotinib as second-line treatment for patients with SCC of the lung, as measured by progression-free survival. Key patient eligibility criteria include: advanced NSCLC squamous or mixed histology, completion of at least 4 cycles of platinum-based doublet chemotherapy, eligible to receive EGFR-directed therapy as second-line therapy, ECOG PS 0–1, adequate organ function, availability of archived tumour tissue for correlative studies and no prior EGFR-directed therapy. Secondary endpoints are comparison of overall survival, objective response rate, disease control rate, tumour shrinkage, assessment of health-related quality of life and safety in both treatment groups. Eligible patients will be randomized (1:1) to receive either afatinib or erlotinib and stratified based on race (East Asian vs. other). Eight hundred patients are planned to be enrolled globally. Independent radiological assessment of the primary endpoint will be completed in a treatment-blinded manner. An independent data monitoring committee will monitor safety and efficacy of the trial. Disclosure G. Goss: Consultant or advisory relationship to Boehringer Ingelheim, compensated prior to conduct of the study. S. Lu: Consultant or advisory relationship, compensated, AstraZeneca China for Iressa. A. Ardizzoni: Other remuneration: GSK DSMC PRAME Study. V. Georgoulias: Consultant or advisory relationship, uncompensated for GSK, Novartis, Sanofi, Janssen-Cilag, Amgen. Honoraria and research funding from GSK, Novartis, Sanofi, Janssen-Cilag, Amgen. S. Gadgeel: Consultant or advisory relationship for Boehringer Ingelheim. V. Chand: Employee of Boehringer Ingelheim Pharmaceuticals, Inc. Y. Gu: Employee of Boehringer Ingelheim Pharmaceuticals, Inc. Y.S. Olivo: Employee of Boehringer Ingelheim Pharmaceuticals, Inc. J. Soria: Honoraria from Boehringer Ingelheim and Roche. All other authors have declared no conflicts of interest.