LUX-Lung 6: A randomized, open-label, phase III study of afatinib (A) vs gemcitabine/cisplatin (GC) as first-line treatment for Asian patients (pts) with EGFR mutation-positive (EGFR M+) advanced adenocarcinoma of the lung

Background: EGFR M+ NSCLC is a distinct lung cancer subtype requiring specific treatment. A is an oral, irreversible, ErbB Family Blocker, blocking EGFR (ErbB1), HER2 (ErbB2) and ErbB4 receptors and subsequent cancer cell growth and survival. This study compared the safety and efficacy of first-line A with GC in EGFR M+ Asian NSCLC pts. Methods: Following central testing for EGFR mutations, 364 pts (Stage IIIB/IV, PS 0–1, chemo-naïve) were randomized 2:1 (A: 242; GC: 122) to daily A 40 mg or IV GC (standard regimen). Primary endpoint was progression-free survival (PFS) by central independent review. Results: Baseline characteristics were balanced in both arms. PFS was significantly prolonged with A compared with GC by independent review (median PFS 11.0 vs 5.6 months, HR=0.28; p<0.0001). Objective response (66.9% vs 23.0%; p<0.0001) and disease control (92.6% vs 76.2%; p<0.0001) rates (ORR/DCR) were significantly higher with A. Most common Grade 3 drug-related AEs were rash/acne (14.6%), diarrhea (5.4%), stomatitis/mucositis (5.4%) with A; neutropenia (17.7%), vomiting (15.9%), leukopenia (13.3%) with GC. Related AEs led to discontinuation in 5.9% (A) and 39.8% (GC) of pts. Patient reported-outcomes and additional safety data will be presented. Conclusions: A significantly improved outcomes (PFS, ORR, DCR) compared with GC in pts with EGFR M+ NSCLC. AEs were as expected, with a more favorable safety profile with A. LUX-Lung 6 is the largest prospective trial in EGFR M+ NSCLC showing that A will be a clinically important option for treatment of these patients.