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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).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] versus1 [PD-L1-negative]).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).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.

Objectives: Advanced vulvar carcinoma typically affects the elderly and treatment options are limited. Moderate antitumor activity of pembrolizumab (ORR, 6%) was noted in a small population of patients (pts) with PD-L1-positive vulvar cancer in the phase 1b KEYNOTE-028 study. KEYNOTE-158 ( ClinicalTrials.gov , NCT02628067) is a larger, nonrandomized, multicohort, open-label, phase 2 study that evaluates pembrolizumab in pts with previously treated advanced cancers irrespective of tumor PD-L1 expression. We report results for pts in the vulvar carcinoma cohort receiving pembrolizumab monotherapy. Methods: Enrolled pts were aged ≥18 y with histologically/cytologically documented advanced vulvar squamous cell carcinoma with prior treatment failure; measurable disease per RECIST v1.1; ECOG performance status ≤1; and tumor samples available for biomarker analysis, including PD-L1. PD-L1 positivity was defined as combined positive score ≥1 with expression evaluated using the PD-L1 IHC 22C3 pharmDx assay (Agilent Technologies, Carpinteria, CA, USA). Pts received pembrolizumab 200 mg Q3W until disease progression, unacceptable toxicity, or completion of 35 treatment cycles. Tumor imaging was performed every 9 weeks for 1 y and every 12 weeks thereafter. Response was assessed per RECIST v1.1 by independent central radiologic review. The primary endpoint was ORR. Secondary endpoints included duration of response (DOR), PFS, OS, and safety. Results: A total of 101 pts were enrolled. As of October 5, 2020, median time from start of treatment to data cutoff was 36.0 (range, 15.4–55.2) months. Median age was 64.0 (range, 31–87) y; 9 (8.9%) pts had no prior therapy, 57 (56.4%) had 1, 23 (22.8%) had 2, and 11 (10.9%) had 3 or more lines of prior therapy. Tumors were PD-L1–positive in 84 pts (83.2%), PD-L1–negative in 7 pts (6.9%), and non-evaluable/not assessed in 10 pts (9.9%). Overall, ORR was 10.9% (95% CI, 5.6–18.7); 1 pt had a CR and 10 pts had PR. Among pts with PD-L1–positive tumors, 8 of 84 (9.5%; 95% CI, 4.2–17.9) had CR or PR; among pts with PD-L1–negative tumors, 2 of 7 (28.6%; 95% CI, 3.7–71.0) had CR or PR. Among pts with a response, median DOR was 20.4 months (range, 2.1+ to 28.0). Among all enrolled pts (n=101), median PFS was 2.1 months (95% CI, 2.0–2.1) and median OS was 6.2 months (95% CI, 4.9–9.4 months). Treatment-related AEs occurred in 51 pts (50.5%), including 12 pts (11.9%) who had grade 3–5 events (no event occurred in >1 pt). There were 2 deaths (2.0%) considered related to treatment (hepatitis, n=1; fulminant hepatitis, n=1). Neither pt had comorbidities or pre-existing liver disease to contribute to these events; no other contributing factors were identified. A total of 5 pts (5.0%) discontinued because of treatment-related AEs. Immune-mediated AEs occurred in 18 pts (17.8%). Conclusions: Pembrolizumab monotherapy was associated with durable responses in a subset of pts with vulvar carcinoma (ORR, 10.9%; median DOR, 20.4 months). Responses occurred in both PD-L1-positive and PD-L1-negative pts.