Journal article
A Phase II Study of Pembrolizumab in EGFR-Mutant, PD-L1+, Tyrosine Kinase Inhibitor Naïve Patients With Advanced NSCLC
Journal of thoracic oncology, Vol.13(8), pp.1138-1145
08/2018
DOI: 10.1016/j.jtho.2018.03.035
PMCID: PMC6063769
PMID: 29874546
Abstract
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%.
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.
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.
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.
Details
- Title: Subtitle
- A Phase II Study of Pembrolizumab in EGFR-Mutant, PD-L1+, Tyrosine Kinase Inhibitor Naïve Patients With Advanced NSCLC
- Creators
- A Lisberg - University of California, Los AngelesA Cummings - University of California, Los AngelesJ W Goldman - University of California, Los AngelesK Bornazyan - University of California, Los AngelesN Reese - University of California, Los AngelesT Wang - University of California, Los AngelesP Coluzzi - University of California, Los AngelesB Ledezma - University of California, Los AngelesM Mendenhall - University of California, Los AngelesJ Hunt - University of California, Los AngelesB Wolf - University of California, Los AngelesB Jones - University of California, Los AngelesJ Madrigal - University of California, Los AngelesJ Horton - University of California, Los AngelesM Spiegel - University of California, Los AngelesJ Carroll - University of California, Los AngelesJ Gukasyan - University of California, Los AngelesT Williams - University of California, Los AngelesL Sauer - University of California, Los AngelesC Wells - University of California, Los AngelesA Hardy - University of California, Los AngelesP Linares - University of California, Los AngelesC Lim - University of California, Los AngelesL Ma - University of California, Los AngelesC Adame - University of California, Los AngelesEdward B Garon - University of California, Los Angeles
- Resource Type
- Journal article
- Publication Details
- Journal of thoracic oncology, Vol.13(8), pp.1138-1145
- DOI
- 10.1016/j.jtho.2018.03.035
- PMID
- 29874546
- PMCID
- PMC6063769
- ISSN
- 1556-0864
- eISSN
- 1556-1380
- Grant note
- R01 CA208403 / NCI NIH HHS P30 CA016042 / NCI NIH HHS
- Language
- English
- Date published
- 08/2018
- Academic Unit
- Orthopedics and Rehabilitation; Physical Therapy and Rehabilitation Science
- Record Identifier
- 9984294952102771
Metrics
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