Combined pembrolizumab and bevacizumab therapy in heavily treated recurrent ovarian cancer

Background: Recurrence in epithelial ovarian cancer (EOC), especially in the late stage, remains a significant challenge, with a five-year survival rate of approximately 40% in advanced-stage disease. A recent phase 2 trial evaluating the combination of pembrolizumab, bevacizumab and oral cyclophosphamide in recurrent EOC demonstrated an objective response rate (ORR) of 47.5%. However, severe adverse events, primarily attributed to cyclophosphamide, were observed in 32.5% of patients. Methods: This retrospective study reviewed the therapeutic response and adverse effects in EOC patients who had received two to three prior lines of chemotherapy and were subsequently treated with pembrolizumab and bevacizumab between 2018 and 2021. Their response rates were assessed using the Gynecological Cancer Intergroup (GCIG) criteria based on serum cancer antigen 125 (CA-125) levels (categorized as response with normalization, response, non-response or progression) or the immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) if baseline CA-125 levels were within the normal range. Results: A total of 12 patients were included, comprising six (50.0%) with high-grade serous carcinoma, three (25.0%) with clear cell carcinoma, one (8.3%) with mucinous carcinoma, one (8.3%) with endometrioid carcinoma, and one (8.3%) with mixed histology. Among them, one patient (8.3%) exhibited a response with normalization of CA-125, four (33.3%) demonstrated a response, four (33.3%) showed no response, and three (25.0%) experienced disease progression. The ORR was 41.7%, with a higher response rate observed in clear cell carcinoma (66.7%), including the patient with response and CA-125 normalization. Notably, no severe adverse effects were reported during treatment. Conclusions: This study differs from prior trials incorporating cyclophosphamide by evaluating pembrolizumab and bevacizumab as a two-drug regimen, potentially offering a less toxic alternative for recurrent ovarian cancer. However, the retrospective design and small sample size necessitate cautious interpretations of the findings, and larger prospective trials are warranted to further investigate the efficacy of this combination.