Optimizing immunotherapy for gynecologic cancers

This review will provide an update on the most recent clinical developments in immuno-oncology in advanced gynecologic cancers and will also highlight ongoing studies in this field.

Although immune checkpoint blockade (ICB) therapy is rapidly altering the treatment landscape in a myriad of solid tumors, the efficacy of ICB therapy with antibodies directed against CTLA-4, PD-1, and PD-L1 in advanced gynecologic cancers has been limited. The exception has been the PD-1 inhibitor pembrolizumab in microsatellite instability high (MSI-H) or mismatch repair-deficient (dMMR) advanced endometrial cancers, highlighted by the recent conditional approval of pembrolizumab in recurrent/metastatic PD-L1-positive cervical cancers and the accelerated approval of pembrolizumab and lenvatinib in microsatellite stable (MSS) or mismatch repair-proficient (pMMR) advanced endometrial cancer. The discovery of novel, rational ICB combinatorial approaches in advanced gynecologic cancers is highly warranted.

Recent advances in the genomic characterization of gynecologic malignancies have informed clinical trial design. However, improved molecular and immunophenotypic biomarkers to more accurately identify patients who will most benefit from immunotherapeutic approaches are urgently needed. This is especially critical as we attempt to integrate immune-oncology agents, chemotherapy, targeted therapy, and radiation therapy in the management of gynecologic cancers.