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

Journal Article (Journal Article)

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) naïve, had superior clinical outcomes to those previously treated with a TKI. As TKI naïve 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 naïve, 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 naïve, 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.

Full Text

Duke Authors

Cited Authors

  • Lisberg, A; Cummings, A; Goldman, JW; Bornazyan, K; Reese, N; Wang, T; Coluzzi, P; Ledezma, B; Mendenhall, M; Hunt, J; Wolf, B; Jones, B; Madrigal, J; Horton, J; Spiegel, M; Carroll, J; Gukasyan, J; Williams, T; Sauer, L; Wells, C; Hardy, A; Linares, P; Lim, C; Ma, L; Adame, C; Garon, EB

Published Date

  • August 2018

Published In

Volume / Issue

  • 13 / 8

Start / End Page

  • 1138 - 1145

PubMed ID

  • 29874546

Pubmed Central ID

  • PMC6063769

Electronic International Standard Serial Number (EISSN)

  • 1556-1380

Digital Object Identifier (DOI)

  • 10.1016/j.jtho.2018.03.035


  • eng

Conference Location

  • United States