Immune Checkpoint Inhibitors in Gynecological Cancers: Update of Literature and Perspectives of Clinical Research

Abstract

The presence of tumor infiltrating lymphocytes (TILs) influences the clinical outcome of cancer patients and immune checkpoint inhibitors (ICPI) have been approved for treating different types of malignancies. In this review, we assess the scanty data from literature and the perspectives of clinical research about the use of ICPI in gynecological cancers. These agents have obtained objective response rates ranging from 5.9% to 15% in early phase Ib-II trials, including patients with platinum-resistant ovarian cancer, whereas only anecdotal data are available for patients with recurrent, heavily pretreated endometrial cancer. Several ongoing trials are investigating ICPI alone or in combination with chemotherapy or with other biological agents in untreated and recurrent ovarian cancer, advanced and recurrent endometrial cancer, as well as advanced and recurrent cervical cancer. Breast cancer (BRCA)-mutated high-grade serous ovarian cancers, clear cell ovarian cancers with microsatellite instability (MSI), POLE ultramutated and MSI hypermutated endometrial cancers are likely to be sensitive to programmed cell death (PD-1)/PD-ligand 1 (PD-L1) pathway blockade, since these tumors show increased neoantigen load, increased CD8⁺ TIL number and PD-1 and PD-L1 overexpression. ICPI could have a role as maintenance treatment in patients with persistent, recurrent or metastatic cervical cancer in response after chemotherapy.

Keywords: CTLA; Immune checkpoint inhibitor; PD-1; PD-L1; cervical cancer; endometrial cancer; epithelial ovarian cancer; review.