P11 Afatinib in Patients with EGFR Mutation-Positive (EGFRm+) NSCLC Harboring Uncommon Mutations: Overview of Clinical Data

Abstract

Approximately 10–12% of patients with EGFRm+ NSCLC have tumors harboring uncommon EGFR mutations; however, there is a paucity of clinical data on the sensitivity of these tumors to EGFR tyrosine kinase inhibitors (TKIs). The clinical activity of afatinib, an irreversible ErbB family blocker, has been assessed in patients with NSCLC harboring certain uncommon EGFR mutations. Here, we review the key clinical data available for afatinib in EGFRm+ NSCLC harboring uncommon EGFR mutations. Post-hoc analysis of the Phase II LUX-Lung 2, and Phase III randomized LUX-Lung 3, and 6, trials1 identified 75 afatinib-treated pts with NSCLC harboring uncommon EGFR mutations not previously treated with a TKI. The objective response rate (ORR) against G719X (n=18), L861Q (n=16) and S768I (n=8) single/compound mutations was 78%, 56% and 100%, respectively. Response rate was lower in patients with exon 20 insertions (n=23; 9%) or de novo T790M (n=14; 14%). In 38 patients with uncommon mutations/duplications in exons 18–21, progression-free survival (PFS) was 10.7 months (95% CI: 5.6–14.7) and overall survival was 19.4 months (95% CI: 16.4–26.9). The clinical activity of afatinib against uncommon mutations is substantiated by observations outside of the clinical trial setting. In a Phase IIIb single-arm open-label study of afatinib, 55 of 479 TKI-naïve patients had NSCLC harboring uncommon mutations.2 Among 35 pts with NSCLC harboring point mutations/duplications in exon 18–21, median PFS was 9.5 months (95% CI: 5.7‒not evaluable [NE]) and time to symptomatic progression was NE (95% CI: 8.2–NE).2 In an analysis of 165 patients with EGFRm+ NSCLC treated with first-line afatinib in real-world practice in South Korea, median PFS in those with uncommon mutations excluding T790M (n=10) was not reached with a median follow-up of 17.7 months (95% CI: 16.2–18.9).3 Afatinib has clinical activity in patients with NSCLC harboring uncommon EGFR mutations, including G719X, L861Q and S768I. These data could help inform clinical decisions in this patient population. 1. Yang. Lancet Oncol 2015;16:830-838 2. Marten. ELCC 2018 #158P 3. Kim. WCLC 2017 P3.01–023