Ovarian Cancer in the Era of Immune Checkpoint Inhibitors: State of the Art and Future Perspectives

SIMPLE SUMMARY: Ovarian cancer (OC) represents the fifth leading cause of cancer-related deaths among women. In the advanced disease setting, OC recurrence after chemotherapy is over 70% in the first 2 years, with few therapeutic options. Immunotherapy with the immune checkpoint inhibitors (ICIs) showed high efficacy and changed the therapeutic scenario of many tumors in the last 10 years. With our review, we aimed to summarize the clinical trials of ICIs in OC. In OC, ICIs clinical trials have reported poor outcomes in terms of patient response and survival, with some studies failing to reach their objectives. Combining immunotherapy with drugs targeting different pathways might enhance efficacy and overcome cancer resistance. The search for biomarkers predicting ICIs response is essential for the identification of patients most likely to benefit from ICI therapy. ABSTRACT: Background: Ovarian cancer (OC) represents the eighth most common cancer and the fifth leading cause of cancer-related deaths among the female population. In an advanced setting, chemotherapy represents the first-choice treatment, despite a high recurrence rate. In the last ten years, immunotherapy based on immune checkpoint inhibitors (ICIs) has profoundly modified the therapeutic scenario of many solid tumors. We sought to summarize the main findings regarding the clinical use of ICIs in OC. Methods: We searched PubMed, Embase, and Cochrane Databases, and conference abstracts from international congresses (such as ASCO, ESMO, SGO) for clinical trials, focusing on ICIs both as monotherapy and as combinations in the advanced OC. Results: 20 studies were identified, of which 16 were phase I or II and 4 phase III trials. These trials used ICIs targeting PD1 (nivolumab, pembrolizumab), PD-L1 (avelumab, aterolizumab, durvalumab), and CTLA4 (ipilimumab, tremelimumab). There was no reported improvement in survival, and some trials were terminated early due to toxicity or lack of response. Combining ICIs with chemotherapy, anti-VEGF therapy, or PARP inhibitors improved response rates and survival in spite of a worse safety profile. Conclusions: The identification of biomarkers with a predictive role for ICIs’ efficacy is mandatory. Moreover, genomic and immune profiling of OC might lead to better treatment options and facilitate the design of tailored trials.