A Phase II Study of Pembrolizumab in EGFR-Mutant, PD-L1+, Tyrosine Kinase Inhibitor Naive Patients With Advanced NSCLC

Background: Despite the significant antitumor activity of pembrolizumab in NSCLC, clinical benefit has been less frequently observed in patients whose tumors harbor EGFR mutations compared to EGFR wild-type patients. Our single center experience on the KEYNOTE-001 trial suggested that pembrolizumab-treated EGFR-mutant patients, who were tyrosine kinase inhibitor (TKI) naive, had superior clinical outcomes to those previously treated with a TKI. As TKI naive EGFR-mutants have generally been excluded from pembrolizumab studies, data to guide treatment decisions in this patient population is lacking, particularly in patients with programmed death ligand 1 (PD-L1) expression >= 50%. Methods: We conducted a phase II trial (NCT02879994) of pembrolizumab in TKI naive patients with EGFR mutation positive, advanced NSCLC and PD-L1-positive (>= 1%, 22C3 antibody) tumors. Pembrolizumab was administered 200 mg every 3 weeks. The primary endpoint was objective response rate. Secondary endpoints included safety of pembrolizumab, additional pembrolizumab efficacy endpoints, and efficacy and safety of an EGFR TKI after pembrolizumab. Results: Enrollment was ceased due to lack of efficacy after 11 of 25 planned patients were treated. Eighty-two percent of trial patients were treatment naive, 64% had sensitizing EGFR mutations, and 73% had PD-L1 expression >= 50%. Only 1 patient had an objective response (9%), but repeat analysis of this patient's tumor definitively showed the original report of an EGFR mutation to be erroneous. Observed treatment-related adverse events were similar to prior experience with pembrolizumab, but two deaths within 6 months of enrollment, including one attributed to pneumonitis, were of concern. Conclusions: Pembrolizumab's lack of efficacy in TKI na ve, PD-L1+, EGFR-mutant patients with advanced NSCLC, including those with PD-L1 expression >= 50%, suggests that it is not an appropriate therapeutic choice in this setting. (C) 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.