Pembrolizumab in vaginal and vulvar squamous cell carcinoma: a case series from a phase II basket trial

Jeffrey A How,Nicole D Fleming,Pamela T Soliman,Jing Gong,Aung Naing,Sarina A Piha-Paul,Filip Janku,Amir A Jazaeri,Bettzy Stephen

doi:10.1038/s41598-021-83317-7

Jeffrey A How, Nicole D Fleming + Show 7 more

Open Access

https://doi.org/10.1038/s41598-021-83317-7

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Abstract

Vaginal and vulvar squamous cell carcinoma (SCC) are rare tumors that can be challenging to treat in the recurrent or metastatic setting. We present a case series of patients with vaginal or vulvar SCC who were treated with single-agent pembrolizumab as part of a phase II basket clinical trial to evaluate efficacy and safety. Two cases of recurrent and metastatic vaginal SCC, with multiple prior lines of systemic chemotherapy and radiation, received pembrolizumab. One patient had significant reduction (81%) in target tumor lesions prior to treatment discontinuation at cycle 10 following confirmed progression of disease with new metastatic lesions (stable disease by irRECIST criteria). In contrast, the other patient with vaginal SCC discontinued treatment after cycle 3 due to disease progression. Both patients had PD-L1 positive vaginal tumors and tolerated treatment well. One case of recurrent vulvar SCC with multiple surgical resections and prior progression on systemic carboplatin had a 30% reduction in her target tumor lesions following pembrolizumab treatment with a PD-L1 positive tumor. Treatment was discontinued for grade 3 mucositis after cycle 5. Pembrolizumab may provide some clinical benefit to some patients with vaginal or vulvar SCC and is overall safe to utilize in this population. Future studies are needed to evaluate the efficacy of pembrolizumab in these rare tumor types and to identify predictive biomarkers of response.

Highlights

Vaginal and vulvar squamous cell carcinoma (SCC) are rare tumors that can be challenging to treat in the recurrent or metastatic setting
Due to the difficulty of performing large prospective randomized trials in these rare tumor populations, systemic chemotherapeutic regimens have generally been extrapolated from experience in the management of cervical cancer as these malignancies share similar epidemiologic risk factors, are predominantly of squamous cell carcinoma (SCC) histologic subtype, and are strongly associated with human papilloma virus (HPV) infection[2,3,4]
Given the propensity of vaginal and vulvar SCC to develop at older stages of life, treatment options may be further limited by associated toxicity and morbidity[3,4]

Summary

Introduction

Vaginal and vulvar squamous cell carcinoma (SCC) are rare tumors that can be challenging to treat in the recurrent or metastatic setting. As the first drug to receive FDA approval for a tissue agnostic indication, pembrolizumab may be of clinical benefit in other solid tumors and possibly among those with HPV-associated gynecologic cancers such as vaginal or vulvar SCC. As part of a clinical phase II basket trial for patients with advanced rare malignancies, we report three cases of SCC (two vaginal and one vulvar) who were treated with single-agent pembrolizumab.

Results

Conclusion