Efficacy and safety of pembrolizumab for patients with previously treated advanced vulvar squamous cell carcinoma: Results from the phase 2 KEYNOTE-158 study

Abstract

Objective: Treatment options for advanced vulvar cancer are limited. We evaluated pembrolizumab monotherapy in patients with advanced vulvar squamous cell carcinoma (SCC) enrolled in the phase 2 multicohort, open-label KEYNOTE-158 study (NCT02628067).

Methods: Eligible patients had histologically or cytologically documented advanced vulvar SCC with prior treatment failure, measurable disease per RECIST v1.1, ECOG performance status 0-1, and a tumor sample available for biomarker analysis. Pembrolizumab 200 mg was administered intravenously Q3W for up to 35 cycles (approximately 2 years). The primary endpoint was objective response rate (ORR) per RECIST v1.1 by independent central radiologic review in all patients and subgroups based on PD-L1 combined positive score (≥1 [PD-L1-positive] versus <1 [PD-L1-negative]).

Results: 101 patients were enrolled. Median time from first dose to data cutoff was 36.0 months. The ORR (95% CI) was 10.9% (5.6%-18.7%) among all patients, 9.5% (4.2%-17.9%) among the 84 patients with PD-L1-positive tumors, and 28.6% (3.7%-71.0%) among the 7 patients with PD-L1-negative tumors. Among patients with a response, median DOR was 20.4 (range, 2.1+ to 28.0) months. Median (95% CI) PFS and OS were 2.1 (2.0-2.1) and 6.2 (4.9-9.4) months, respectively. Treatment-related AEs occurred in 50.5% of patients (grade 3-5, 11.9%) and led to discontinuation of treatment in 5.0% of patients. Two deaths were considered treatment-related (hepatitis, n = 2).

Conclusions: Pembrolizumab monotherapy was associated with durable responses in a subset of patients with vulvar SCC. Responses occurred regardless of tumor PD-L1 status. No new safety signals emerged; overall, pembrolizumab was well tolerated.

Keywords: KEYNOTE-158; Monotherapy; Pembrolizumab; Vulvar cancer.

Conflict of interest statement

Declaration of competing interest Ronnie Shapira-Frommer: study funding to the institution from Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD), to support study conduct; honoraria for serving as a speaker from MSD, BMS, AstraZeneca, Novartis, and Roche; personal fees for advisory boards from MSD, Clovis Oncology, and VBL Therapeutics. Linda Mileshkin: study funding to the institution from MSD to support study conduct. Ludmila Manzyuk: study funding to the institution from MSD to support study conduct. Nicolas Penel: study funding to the institution from MSD to support study conduct. Sarina A. Piha-Paul: study funding to the institution from MSD to support study conduct; clinical trial research support from AbbVie, Inc., ABM Therapeutics, Inc., Acepodia, Inc., Alkermes, Aminex Therapeutics, Amphivena Therapeutics, Inc., BioMarin Pharmaceutical, Inc., Boehringer Ingelheim, Bristol Myers Squibb, Cerulean Pharma, Inc., Chugai Pharmaceutical Co., Ltd., Curis, Inc., Cyclacel Pharmaceuticals, Daiichi Sankyo, Eli Lilly, ENB Therapeutics, Five Prime Therapeutics, F-Star Beta Limited, F-Star Therapeutics, Ltd., Gene Quantum, Genmab A/S, GlaxoSmithKline, Helix BioPharma Corp., HiberCell, Inc., Immunomedics, Inc., Incyte Corp., Jacobio Pharmaceuticals Co., Ltd., Lytix Biopharma AS, MedImmune, LLC, Medivation, Inc., Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Novartis Pharmaceuticals, Pieris Pharmaceuticals, Inc., Pfizer, Principia Biopharma, Inc., Puma Biotechnology, Inc., Rapt Therapeutics, Inc., Seattle Genetics, Silverback Therapeutics, Synlogic, Taiho Oncology, Tesaro, Inc., TransThera Bio, and NCI/NIH (CCSG Shared Resources Grant# P30Ca016672). Matthew Burge: honoraria and study funding to the institution from MSD to support study conduct. Eugenia Girda: study funding to the institution from MSD to support study conduct. Jose A. Lopez Martin: study funding to the institution from MSD to support study conduct; grants, personal fees, and non-financial support from MSD during the conduct of the study; grants, personal fees, and non-financial support from BMS; grants from Merck-Serono; grants and personal fees from Pfizer; personal fees from Bayer|grants and personal fees from Lilly; grants, personal fees, and non-financial support from PharmaMar; grants, personal fees, and non-financial support from Roche; grants and personal fees from Novartis; and personal fees from Pierre-Fabre; current employee of PharmaMar (beginning after this study was conducted). Marloes G.J. van Dongen: study funding to the institution from MSD to support study conduct. Antoine Italiano: study funding to the institution from MSD to support study conduct, grants from MSD, grants from BMS, grants and personal fees from Bayer, personal fees from Springworks, grants from AstraZeneca, grants and personal fees from Roche, grants from Ipsen, grants from PharmaMar. Lei Xu: employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Owns stock in Merck & Co., Inc., Kenilworth, NJ, USA. Fan Jin: employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Owns stock in Merck & Co., Inc., Kenilworth, NJ, USA. Kevin Norwood: employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Owns stock in Merck & Co., Inc., Kenilworth, NJ, USA. Patrick Ott: study funding to the institution from MSD to support study conduct; grants from BMS, Genentech, Celldex, Cytomx, Pfizer, Neon Therapeutics, Armo Biosciences, AstraZeneca, Xencor, and Oncorus; personal fees from Alexion, Amgen, BMS, Genentech, Celldex, Cytomx, Pfizer, Novartis, Neon Therapeutics (now BioNTechUS), and Array.

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