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

Shapira-Frommer, R; Mileshkin, L; Manzyuk, L; Penel, N; Burge, M; Piha-Paul, SA; Girda, E; Lopez Martin, JA; van Dongen, MGJ; Italiano, A; Xu, L; Jin, F; Norwood, K; Ott, PA

Author(s): Shapira-Frommer, R; Mileshkin, L; Manzyuk, L; Penel, N; Burge, M; Piha-Paul, SA; Girda, E; Lopez Martin, JA; van Dongen, MGJ; Italiano, A; Xu, L; Jin, F; Norwood, K; Ott, PA;
Details: Publication Year 2022-08,Volume 166,Issue #2,Page 211-218
Journal Title: Gynecologic Oncology
Publication Type: Research article
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: Antibodies, Monoclonal, Humanized/adverse effects; B7-H1 Antigen/metabolism; *Carcinoma, Squamous Cell/drug therapy; Female; Humans; *Vulvar Neoplasms/drug therapy; Keynote-158; Monotherapy; Pembrolizumab; Vulvar cancer
Department(s): Medical Oncology
PubMed ID: 35361487
Publisher's Version: https://doi.org/10.1016/j.ygyno.2022.01.029
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-04-04 12:33:49

Last Modified: 2025-04-04 12:35:17