Efficacy and Safety of Targeted Therapy and Immunotherapy in Advanced Vulvar Squamous Cell Carcinoma: A Scoping Review.

Introduction: Vulvar squamous cell carcinoma (VSCC) is a rare gynecological tumor with limited treatment options for advanced stages. Current chemotherapy, adapted from cervical cancer protocols, often results in poor outcomes. This scoping review evaluates the efficacy and safety of immunotherapy and targeted therapies in advanced VSCC.

Material And Methods: After extensive assessment, examination, and curation of relevant literature data, eight trials focused on immunotherapy or targeted therapy for advanced, recurrent, or metastatic VSCCs were identified and selected. The findings have been compiled and synthesized into a narrative overview, adhering to the PRISMA-ScR guidelines.

Results: The study analyzed four unpublished and four published trials, evaluating the efficacy and safety of immunotherapy or targeted therapy for VSCCs. Pembrolizumab was assessed in the KEYNOTE-028 and KEYNOTE-158 trials, showing objective response rates (ORRs) of 6% and 10.9%, respectively, and median overall survival (OS) between 3.8 and 6.2 months. CheckMate 358 reported a 20% ORR for nivolumab. Combination strategies (ipilimumab plus nivolumab and pembrolizumab plus vorinostat) demonstrated efficacy with median OS of 7.6 and 17.5 months, respectively. Toripalimab showed an ORR of 33.3%. Safety profiles were generally manageable, with common adverse events like fatigue and gastrointestinal disorders. Serious adverse events included grade 5 immune-related hepatitis and chronic kidney disease.

Conclusion: Immunotherapy may be considered an option for VSCCs in the second-line setting. Despite the limited research on targeted therapies for VSCCs, combination approaches with immunotherapy demonstrate promising potential. Prioritizing the identification of biomarkers that predict responses to immune checkpoint inhibitors is essential.