KEYNOTE-100 (NCT02674061) showed pembrolizumab (pembro) has clinical activity in patients (pts) with advanced ovarian cancer (AOC), and PD-L1 expression (combined positive score [CPS] ≥10) was associated with response. Other biomarkers possibly associated with response were evaluated.
Key inclusion criteria included epithelial ovarian, fallopian tube, or primary peritoneal cancer, confirmed recurrence following front-line platinum-based therapy, ECOG PS 0/1, and tumor sample. Pts received pembro 200 mg Q3W IV for 2 y or until progression, death, unacceptable toxicity, or consent withdrawal. Whole exome sequencing of paired tumor and normal samples determined homologous recombination deficiency genomic scar (HRD) and BRCA1/2 mutation status (BRCA) using standard algorithms. Associations of response with T-cell-inflamed 18-gene expression profile (T-cell-GEP) score, HRD, BRCA, and microsatellite instability-high (MSI-H) were evaluated.
T-cell-GEP, BRCA, and HRD data were available from the first 100 pts enrolled, while MSI-H was from the entire study population (n=319). Among patients with T-cell-GEP, distribution of GEP scores was significantly higher in responders than nonresponders (1-sided p=0.03 from Wilcoxon rank sum test; n=83). 7/83 pts (8.4%) had a response. In pts with available PD-L1 CPS and GEP (n=79; Spearman’s correlation ρ=0.57), the area under the receiver characteristic curves for CPS and T-cell-GEP were numerically similar (0.73 vs 0.72, respectively). No statistically significant differences were observed with HRD values among responders and nonresponders (1-sided p=0.29; n=71). No association between BRCA status (n=11 mutant; n=60 wild type) and response was observed (1-sided p=0.65). 6/71 pts (8.5%) in this population had a response. Of 319 paired samples tested for MSI-H, all were MSS.
In addition to PD-L1 CPS, T-cell-GEP was associated with a response to pembro monotherapy for treatment of AOC in a single-arm setting, while HRD biomarkers (HRD, BRCA) were not found to be associated with response.
Clinical trial identification
NCT02674061; release date, February 25, 2016
Medical writing assistance was provided by Christine McCrary Sisk, an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and by Matthew Grzywacz, ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.