Current Possibilities of Gynecologic Cancer Treatment with the Use of Immune Checkpoint Inhibitors

Abstract

Despite the ongoing progress in cancer research, the global cancer burden has increased to 18.1 million new cases and 9.6 million deaths in 2018. Gynecological cancers, such as ovarian, endometrial, and cervical cancers, considerably contribute to global cancer burden, leading to $5,862.6, $2,945.7, and $1,543.9 million of annual costs of cancer care, respectively. Thus, the development of effective therapies against gynecological cancers is still a largely unmet medical need. One of the novel therapeutic approaches is to induce anti-cancer immunity by the inhibition of the immune checkpoint pathways using monoclonal antibodies. The molecular targets for monoclonal antibodies are cytotoxic T lymphocyte-associated protein-4 (CTLA-4), programmed cell death protein-1 (PD-1), and programmed death-ligand 1 (PD-L1). The rationale for the use of immune checkpoint inhibitors in patients with gynecological cancers was based on the immunohistological studies showing high expression levels of PD-1 and PD-L1 in those cancers. Currently available immune checkpoint inhibitors include nivolumab, pembrolizumab, atezolizumab, avelumab, durvalumab, and ipilimumab. The efficacy and safety of these inhibitors, used as monotherapy and with combination with chemotherapy, is being currently evaluated in several clinical studies. As the results are promising, more clinical trials are being planned, which may lead to the development of efficient therapies for gynecological cancer patients.

Immune Checkpoint Blockade in Gynecologic Cancers: State of Affairs

“…Combination therapy has the potential to afford additive or synergistic benefits, as compared to single agent treatment, as well as to overcome resistance mechanisms that are observed with ICI monotherapy administration, due to the upregulation of alternative immune checkpoint molecules or to emerging resistance caused by the presence of cells such as myeloid-derived suppressor cells (MDSCs) [61][62][63][64][65]. Currently, several clinical trials are ongoing with ICI treatment in EC patients, which are used in combination with cytotoxic chemotherapy, other ICI, vaccines and other immunotherapies, or targeted therapies [25,26,29,32,66].…”

“…Other ovarian cancer clinical trials investigating ICI and in combination with other agents are summarized elsewhere [66,[131][132][133]. The outcome of these trials and the modest success rate to ICI when used in monotherapy or in combination therapy for ovarian cancer indicates that there are yet many unknowns in the realm of ICI therapy.…”

Predictive Values of Programmed Cell Death-Ligand 1 Expression for Prognosis, Clinicopathological Factors, and Response to Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Inhibitors in Patients With Gynecological Cancers: A Meta-Analysis

“…Although several therapeutic options (i.e. surgery, chemoradiotherapy and immunotherapy) have been recommended recently, some patients exhibit a poor response to these management strategies and experience relapses or metastases, ultimately dying from their diseases ( 4 ). Therefore, predictive biomarkers may be urgently necessary to early stratify these patients at a high risk of poor responses and unfavorable outcomes and then guide more individualized treatment regimens to further improve overall survival (OS).…”

Six-lncRNA Immune Prognostic Signature for Cervical Cancer

“…Immunotherapy is one of the most promising tools that may be used in future cervical cancer treatments. Immunotherapies consisting of anti-CTLA4 and anti-PD1 drugs have demonstrated efficacy in oropharyngeal cancer and cervical cancer ( Dorta-Estremera et al, 2019 ; Grywalska et al, 2019 ). The combination of the immune checkpoint blockade PD1 and HPV16 E6/E7-targeted therapy can induce better anti-tumor effects ( Dorta-Estremera et al, 2019 ; Zhen et al, 2019 ).…”