LUX-Lung 8: A Global Phase III Trial of Afatinib (A) vs Erlotinib (E) as Second-Line Treatment in Patients (Pts) With Advanced Squamous Cell Carcinoma (SCC) of the Lung Following First-Line Platinum-Based Chemotherapy

SESSION TITLE: Lung Cancer Treatment & Outcomes SESSION TYPE: Original Investigation Slide PRESENTED ON: Wednesday, October 28, 2015 at 07:30 AM - 08:30 AM PURPOSE: Effective treatments are needed for pts with SCC of the lung. Up to 85% of SCC lung tumors overexpress EGFR. Other ErbB receptors (HER2–4) and their downstream signaling pathways have also been implicated in the pathogenesis of SCC, providing rationale to develop tyrosine kinase inhibitor (TKI) treatment options. LUX-Lung 8 compared A, an irreversible ErbB family blocker, and E, a reversible EGFR TKI approved in this setting, in pts with SCC of the lung following failure of platinum-based chemotherapy. METHODS: 795 pts with stage IIIB/IV SCC were randomized 1:1 to receive A (40 mg/day; n=398) or E (150 mg/day; n=397) until progression. Primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS; to be reported after 632 deaths), objective response rate (ORR), disease control rate (DCR), patient-reported outcomes, and safety. Here we report the planned primary analysis after 414 PFS events had occurred while recruitment was ongoing. RESULTS: PFS was significantly improved for A vs E (median 2.4 vs 1.9 mos; HR [95% CI]: 0.82 [0.68-1.00]; p=0.043). A differentiation of PFS curves started at ~2 mos (first imaging time point) and significant differences in PFS were observed at 3 (42.9 vs 33.6%; p=0.032), 6 (22.1 vs 13.7%; p=0.040), and 9 (15.4 vs 7.4%; p=0.035) mos. More pts treated with afatinib achieved an objective response (ORR: 4.8 vs 3.0%; p=0.233); median duration of response was 9.2 vs 3.7 mos. DCR was significantly improved with A vs E (45.7 vs 36.8%; p=0.020). More pts had improved global health status/quality of life (HRQoL; 36.4 vs 27.1%; p=0.026), cough (43.6 vs 32.6%; p=0.010) and dyspnea (49.4 vs 44.8%; p=0.298) with A than E. Significantly fewer pts treated with A took pain medication (41.9% vs 51.8%; p=0.011). Median duration of exposure (59 and 57 days) and grade ≥3 adverse events (AEs; 50.2 and 49.1%) were similar with A and E. Interim results showed a trend towards improved OS with A; primary analysis of OS and preliminary results from next-generation sequencing of select tumor samples will be presented. CONCLUSIONS: A improved PFS, DCR and HRQoL compared with E, with manageable AEs. Final, updated data including OS, PFS and HRQoL will be presented. Positive OS may confirm A as a future second-line therapy option in SCC of the lung. CLINICAL IMPLICATIONS: The LUX-Lung 8 primary analysis provides encouraging data to support A as a future second-line treatment option for pts with SCC of the lung. DISCLOSURE: Vera Hirsh: Consultant fee, speaker bureau, advisory committee, etc.: Boehringer Ingelheim advisory board member Shirish Gadgeel: Consultant fee, speaker bureau, advisory committee, etc.: Consultant fees from Boehringer Ingelheim Jean-Charles Soria: Consultant fee, speaker bureau, advisory committee, etc.: Personal fees from Boehringer Ingehleim Enriqueta Felip: Consultant fee, speaker bureau, advisory committee, etc.: Consultation fees from Lilly, Pfizer, Roche and Boehringer Ingelheim, Consultant fee, speaker bureau, advisory committee, etc.: Speaker's bureaus for AstraZeneca and Novartis Shun Lu: Consultant fee, speaker bureau, advisory committee, etc.: Consulting fees from Boehringer Ingelheim Vassilis Georgoulias: Consultant fee, speaker bureau, advisory committee, etc.: Honoraria from GlaxoSmithKline, Novartis, Sanofi, Janssen-Cilag, Amgen, Astellas and Boehringer Ingelheim, Consultant fee, speaker bureau, advisory committee, etc.: Consulting/advisory fees from GlaxoSmithKline, Novartis, Sanofi, Janssen-Cilag, Amgen and Boehringer Ingelheim, Grant monies (from industry related sources): Research funding from GlaxoSmithKline, Novartis, Sanofi, Janssen-Cilag, Amgen and Boehringer Ingelheim Andrea Ardizzoni: Consultant fee, speaker bureau, advisory committee, etc.: Advisory board fees from Eli Lilly, Bristol-Myers Squibb, MSD, Boehringer Ingelheim and Merck Jamie Cromer: Employee: Employee of Boehringer Ingelheim Bushi Wang: Employee: Employee of Boehringer Ingelheim Vikram Chand: Employee: Employee of Boehringer Ingelheim The following authors have nothing to disclose: Manuel Cobo, Konstantinos Syrigos, Ki Hyeong Lee, Erdem Göker, Wei Li, Dolores Isla, Salih Zeki Guclu, Alessandro Morabito, Young Joo Min, Glenwood Goss No Product/Research Disclosure Information