Current and emerging immunotherapies for recurrent cervical cancer

Approximately 4290 women in the United States and 311,000 women worldwide died of cervical cancer in 2021. The management of advanced, recurrent, and/or metastatic cervical cancer has been a difficult and frustrating task owing to the paucity of available treatments. The year 2021 proved to be a boon for oncologists and their patients with cervical cancer, however, thanks to the release of data from KEYNOTE-826, which led to the approval of pembrolizumab in combination with chemotherapy, as well as the full approval of pembrolizumab alone, in the first-line setting. By January of 2022, it is likely that cemiplimab will be approved for recurrent or metastatic cervical cancer. With the availability of programmed death 1 (PD-1) inhibition in the first-line setting, it becomes important to discuss the future of second-line treatment, given that combination immunotherapy treatment that includes a PD-1 inhibitor after initial PD-1 treatment has been proved effective in the melanoma setting. Proposed and trialed combinations in immunotherapy include PD-1 inhibition with anti-T-cell immunoreceptor with Ig and ITIM domains (TIGIT) agents, anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) agents, and long-peptide vaccine. This review discusses the KEYNOTE-158 and KEYNOTE-826 trials of pembrolizumab, along with the EMPOWER CERVICAL 1 (R2810-ONC-1676/GOG 3016/ENGOT cx9) trial of cemiplimab and a phase 3 trial of balstilimab in cervical cancer. It also discusses the rationale for the use of immunotherapy in the cervical cancer setting, the mechanisms of action of available and currently studied immunotherapies, biomarkers for predicting and assessing response to treatment, and mechanisms of secondary tumoral escape or resistance to immunotherapy.