Beyond extrapolation: Immunotherapy outcomes in recurrent vulvovaginal carcinoma

OBJECTIVES: To evaluate the efficacy, survival outcomes, and toxicity of immune checkpoint inhibitors (ICI) in patients with recurrent vulvar and vaginal carcinomas (VVC). METHODS: This retrospective cohort study included patients with recurrent VVC treated with ICI at a single tertiary care center between August 2016 and September 2025. Treatment response was assessed using RECIST 1.1 criteria. Objective response rate (ORR), duration of response (DOR), progression-free survival (PFS) and overall survival (OS) were evaluated. Survival outcomes were estimated using the Kaplan-Meier method. RESULTS: Twenty-one patients with recurrent VVC received ICI therapy, with a median age of 73.0 years (IQR, 62.4-77.9); 17 were evaluable for response. PD-L1 expression was positive (CPS ≥1) in 85.7% (n = 18). Pembrolizumab was the most administered ICI (76.2%, 16/21), and most patients received ICI monotherapy (66.7%, 14/21). The median number of ICI cycles was 4 (IQR, 2-6). The ORR was 29.4% (n = 5) with a median DOR of 14.0 months (IQR, 4.97-16.0). Median PFS was 3.0 months (95% CI 1.9-3.4) and median OS was 4.6 months (95% CI 3.7-8.5). Median PFS was 3.1 months for patients receiving combination therapy and 2.5 months for those receiving monotherapy (p = 0.50). Immune-related adverse events occurred in 38.1% (n = 8), including grade ≥ 3 events in 19.0% (n = 4). Disease progression was the most common reason for treatment discontinuation (57.1%, n = 12). CONCLUSIONS: ICI demonstrated modest activity in recurrent VVC, with durable responses observed in a small subset of patients. Although survival outcomes were limited overall, ICI therapy may provide meaningful benefit for select patients.