Abstract
Immunotherapy has changed the natural history of several malignancies that, a decade ago, had a very poor prognosis, such as lung cancer and melanoma. Consequently, many attempts have been done to expand the indications of immunotherapy agents, predominantly immune checkpoint inhibitors (ICIs), in other cancers, including gynecological malignancies. Alongside promising results in cervical and endometrial neoplasms, there are not clear data on the benefit of ICIs as single agent or in combination with antiangiogenic agents in ovarian cancer (OC) and ongoing trials are focusing on combining ICIs with standard chemotherapy or PARP inhibitors. This chapter summarized the evidences of ICIs in gynecological malignancies and report the ongoing trials in cervical, endometrial and OC.
Highlights
In the last decade immunotherapy has revolutionized the course of several cancers, such as lung, melanoma, and urogenital cancers.Immunotherapy essentially acts by boosting the endogenous immune system against tumor cells
In a preliminary phase Ia study atezolizumab was administered at the dose of 1,200 mg q3weeks to 15 advanced endometrial cancer (EC) patients reporting an overall response rate (ORR) of 13% and a disease control rate (DCR) of 26% without significant treatment related adverse events (AEs); it is worth noting that in tumors presenting both elevated programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs), the ORR appeared higher [36]
The rationale for combining immunotherapy with antiangiogenic agents lies on the ability of the latter to enhance T cell trafficking and infiltration into the tumor microenvironment [64]: in preclinical models, the inhibition of vascular endothelial growth factor (VEGF) signaling promoted antitumor immunity and enhanced the efficacy of immune checkpoint blockade [65], the combination of anti-VEGF and antiPD-L1 showed a synergistic anti-tumor effect in vivo [66]
Summary
In the last decade immunotherapy has revolutionized the course of several cancers, such as lung, melanoma, and urogenital cancers. Passive immunotherapy consists in administering immune compounds produced exogenously, stimulating an anti-tumor immune response The latter, includes immune checkpoint inhibitors (ICIs) and adoptive T cell therapy (ACT) [1]. In patients with PD-L1–positive tumors where 14.6% ORR was registered and the median DoR was not reached; 65.3% of patients experienced treatment-related AEs (12.2% grade ≥ 3), mainly hypothyroidism (10.2%), decreased appetite (9.2%), and fatigue (9.2%) [11] Based on this data, in June 2018 the FDA approved pembrolizumab for the treatment of advanced/recurrent, previously treated, CPS ≥ 1 CC, with CPS being the ratio of PD-L1 staining cells (both tumor cells, and immune cells) to the total number of viable tumor cells × 100. Besides the trials above mentioned (Table 1), ongoing trials are exploring the role of ICIs combined with chemo-radiation CX-11 [14], or neo-adjuvant chemotherapy MITO CERV 3 [15], in locally advanced disease, and in combination with systemic platinum-based chemotherapy in the advanced setting, either in chemo-naïv e patients (KEYNOTE-826 [16] and BEAT-CC trial [17]) or in previously treated patients (CX-8 GEMAB [18] and CX-9 REGENERON trial [19])
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