# Immunotherapy and Advanced Vulvar Cancer: A Systematic Review and Meta-Analysis of Survival and Safety Outcomes

## TL;DR

This study reviews the use of immunotherapy in advanced vulvar cancer, finding modest effectiveness and acceptable safety, but highlights the need for better patient selection and biomarkers.

## Contribution

The study provides the first meta-analysis of immune checkpoint inhibitors in advanced vulvar squamous cell carcinoma, emphasizing response variability and biomarker needs.

## Key findings

- Pooled objective response rate to immunotherapy was 21% in advanced vulvar cancer.
- Combination therapy showed higher response rates (46%) compared to monotherapy (11%).
- Treatment-related adverse events occurred in 73% of patients, with 3% treatment-related deaths.

## Abstract

Advanced and recurrent vulvar squamous cell carcinoma remains difficult to treat, with limited therapeutic options and poor survival outcomes. Immune checkpoint inhibitors have shown promise in other HPV-associated cancers, but their role in VSCC is less defined. This systematic review and meta-analysis synthesized the current evidence on ICIs in advanced VSCC, demonstrating encouraging response rates in this challenging setting, with acceptable toxicity. Our findings highlight key limitations in biomarker reporting and underscore the need for more precise patient selection. This work provides a foundation for future clinical trials and biomarker-driven strategies aimed at improving outcomes in this rare and aggressive disease.

Background: Advanced and recurrent vulvar squamous cell carcinoma (VSCC) presents a major therapeutic challenge with limited treatment options and poor outcomes. Immune checkpoint inhibitors (ICIs) have shown efficacy in other HPV-associated malignancies, but their role in VSCC remains poorly defined due to the rarity of the disease and limited clinical trial data. Methods: We conducted a systematic review and meta-analysis following PRISMA guidelines and registered in PROSPERO (CRD420251067565). A comprehensive literature search identified prospective clinical trials evaluating ICIs in patients with advanced, unresectable, recurrent, or metastatic VSCC. The primary outcomes included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Risk of bias was assessed using the MINORS tool. Meta-analyses were performed using random-effects models, with subgroup analyses based on PD-L1 status and treatment regimens (monotherapy vs. combination therapy). Results: Six non-randomized single-arm trials involving 181 patients were included. The pooled ORR was 21%, with higher response rates observed in combination therapy (46%) compared to monotherapy (11%), though not statistically significant. Median PFS and OS were 2.2 months and 6.4 months, respectively. ORRs were similar between PD-L1-positive and PD-L1-negative subgroups. A safety analysis showed treatment-related adverse events (AEs) in 73% of patients and grade ≥ 3 AEs in 23%. The incidence of treatment-related death was 3%. Conclusions: ICIs demonstrate modest but durable efficacy and an acceptable safety profile in advanced VSCC. The current evidence supports their use in selected patients. However, response variability and the lack of reliable predictive biomarkers, such as PD-L1 or HPV status, underscore the need for biomarker-driven clinical trials and improved patient selection strategies.