The role of immune checkpoint inhibition in the treatment of ovarian cancer

Abstract

The introduction of immune checkpoint inhibitors has revolutionized treatment of multiple cancers and has bolstered interest in this treatment approach. So far, emerging clinical data show limited clinical efficacy of these agents in ovarian cancer with objective response rates of 10-15% with some durable responses. In this review, we present emerging clinical data of completed trials of immune checkpoint inhibitors and review ongoing studies. In addition we examine the current knowledge of the tumor microenvironment of ovarian cancers with a focus on the significance of PD-L1 expression and tumor-infiltrating lymphocytes on predicting response to immune checkpoint blockade. We evaluate approaches to improve treatment outcomes through the use of predictive biomarkers and patient selection. Finally, we review management considerations including immune related adverse events and response criteria.

Keywords: CTLA-4; Fallopian tube cancer; Immune checkpoint inhibitors; Immunotherapy; Ovarian cancer; PD-1; PD-L1; Primary peritoneal cancer.

Fig. 1

Costimulatory and coinhibitory pathways regulate the T-cell response to antigen. APC: antigen-presenting cell, CTLA-4: cytotoxic T lymphocyte-associated protein 4, MHC: major histocompatibility complex, PD-1: programmed cell death protein 1; PD-L1: PD-1 ligand, TCR: T-cell receptor

Fig. 2

Ongoing or planned phase 3 trials in ovarian cancer with immune checkpoint inhibitors. a NCT02718417: Javelin Ovarian 100. b ENGOT-ov29-GCIG: ATALANTE. c NCT02580058: Javelin Ovarian 200. d NRG-GY009