Pembrolizumab Induces Notable Response Rate in Patients With Pretreated Vulvar Squamous Cell Carcinoma

Patients with heavily pretreated vulvar squamous cell carcinoma experienced responses with pembrolizumab monotherapy in a nonrandomized phase 2 trial, regardless of PD-L1 status.

Results of the phase 2 KEYNOTE-158 trial (NCT02628067) that were presented at the Society of Gynecological Oncology (SGO) 2021 Virtual Annual Meeting on Women’s Cancer demonstrated that patients with previously treated vulvar squamous cell carcinoma who received single-agent pembrolizumab experienced durable responses, and this was seen across PD-L1 expression levels.

In the nonrandomized, multicohort, open-label study, investigators saw an objective response rate (ORR) of 10.9% (95% CI, 5.6%-18.7%) in patients with vulvar squamous cell carcinoma treated with pembrolizumab. One patient had a complete response (CR) and 10 patients had a partial response (PR). Responses were also found to be durable with a median duration of response (DOR) of 20.4 months after a median follow-up of 36 months (range, 15.4-55.2) among responding patients.

“Although 11% had a confirmed response to the study, irrespective of PD-L1 status, another 18% [had] stable disease, making an overall clinical benefit rate of 28.7%,” explained Ronnie Shapira Frommer, MD, who presented the abstract on KEYNOTE-158 at the virtual event. According to Frommer, this was a meaningful treatment group (n = 101) because there is currently no standard of care. Of note, 95 patients discontinuing treatment at some point during the study.

Stratifying outcomes by PD-L1 tumor status, both positive and negative tumors had meaningful responses to pembrolizumab monotherapy. Eight of 84 patients with a PD-L1–positive status responded, for an ORR of 9.5% (95% CI, 4.2%-17.9%), one of whom had a CR and 7 with PRs. In comparison, of the 7 patients with tumors that were PD-L1 negative, 2 had PRs for an ORR of 28.6% (95% CI, 3.7%-71%).

In the overall treatment population, median progression-free survival (PFS) was 2.1 months (95% CI, 2.0-2.1) with a median overall survival (OS) of 6.2 months (95% CI, 4.9-9.4). The OS rate was considered meaningful by the investigators, as 50.5% of the patients were alive after 6 months and 14% were alive after 24 months.

Only 3.6% of 78 patients from baseline saw a reduction in tumor size, but responses were still evident in both patients with PD-L1–positive and -negative status, said Frommer, director of the Ella Lemelbaum Institute for Immuno-Oncology and head of the Onco-Gynecological Unit at the Sheba Medical Center in Israel. These responses were also evident in the first and second rounds of treatment follow-up.

Enrolled patients were 18 years or older who had advanced vulvar squamous cell carcinoma with prior treatment failure and an ECOG performance status of 0 or 1. PD-L1 positivity in tumors was defined as a combined positive score of 1 or more evaluated by using the PD-L1 IHC 22C3 pharmDx assay. Pembrolizumab at 20 mg was given to patients once every 3 weeks until disease progression, unacceptable toxicity, or completion of 35 treatment cycles. Tumor imaging was done every 9 weeks for 1 year and every 12 weeks afterward. The primary end point of the study was ORR with secondary end points including DOR, PFS, OS, and safety.

Safety of pembrolizumab monotherapy was in line with other studies of the drug and immune checkpoint inhibitors as a whole. Fifty percent of patients on the study experienced adverse events (AEs) with 11% considered grade 3 or above; 5% of patients discontinued treatment due to AEs. Other discontinuations from the trial were due to radiologic disease progression (46.5%), clinical disease progression (29.7%), and consent withdrawal (4%).

The most common treatment-related AE was nausea experienced by 7.9% of patients, followed by diarrhea (6.9%), hypothyroidism (6.9%), asthenia (5.9%), decreased appetite (5.9%), fatigue (5.9%), pruritus (5.9%), hyperthyroidism (5%), and rash (5%). There were 2 cases of treatment-related death due to severe hepatitis. Eighteen percent of patients that experienced a treatment-related AE experienced endocrinopathy.

Immune-mediated AEs were experienced at any grade by 17.8% of patients with 5.9% experiencing AEs grade 3 or above. This led to discontinuation of treatment in 3% of patients. The most common immune-mediated AEs were hypothyroidism (9.9%), hyperthyroidism (5.9%), pneumonitis (3%), hepatitis (2%), severe skin reaction (2%), colitis (1%), thyroiditis (1%), and vasculitis (1%).


Frommer RS, Mileshkin L, Manzyuk L, et al. Pembrolizumab for Vulvar Squamous Cell Carcinoma: Results From the Phase 2 KEYNOTE-158 Study. Abstract presented at: Society of Gynecological Oncology 2021 Virtual Annual Meeting on Women’s Cancer; March 19-21, 2021; Virtual. Abstract 11603.