For a study, researchers sought to find a few alternatives for treating advanced vulvar carcinoma. Patients in phase 2 multicohort, open-label KEYNOTE-158 study with advanced vulvar squamous cell carcinoma (SCC) were examined for response to pembrolizumab monotherapy (NCT02628067). Patients qualified if they had detectable illness according to RECIST v1.1, ECOG performance status 0-1, histologically or cytologically confirmed advanced vulvar SCC, prior therapy failure, and a tumor sample accessible for biomarker analysis. Intravenously, 200 mg of pembrolizumab was given Q3W for up to 35 cycles (about 2 years). In all patients and subgroups based on PD-L1 combined positive score (≥1 [PD-L1-positive] versus <1 [PD-L1-negative]), the objective response rate (ORR) per RECIST v1.1 was the main goal. There were 101 patients enrolled. The median period between the first dose and the data cutoff was 36.0 months. The ORR (95% CI) was 10.9% (5.6%-18.7%) for all patients was 9.5% (4.2%-17.9%), for the 84 patients with PD-L1-positive tumours it was 9.5% (4.2%-17.9%), and for the 7 patients with PD-L1-negative tumours it was 28.6% (3.7%-71.0%). The median decreased ovarian reserve (DOR) was 20.4 months (range 2.1+ to 28.0) among patients with a response. The median (95% CI) PFS and OS were, respectively, 2.1 (2.0-2.1) and 6.2 (4.9-9.4) months. About 50.5% of patients experienced treatment-related adverse events (AEs) (grade 3-5, 11.9%), and 5.0% of patients had their therapy stopped as a result. About 2 deaths (hepatitis, n=2) were thought to be connected to therapy. Pembrolizumab monotherapy was linked to long-lasting responses in a subset of individuals with vulvar SCC. Regardless of tumor PD-L1 status, responses happened. Pembrolizumab was generally well tolerated; no new safety indications were noted.