PARP and PD-1/PD-L1 checkpoint inhibition in recurrent or metastatic endometrial cancer. (August 2020)

• Record Type: Journal Article
• Authors: Post, Cathalijne C.B.; Westermann, Anneke M.; Bosse, Tjalling; Creutzberg, Carien L.; Kroep, Judith R.
• Is Part Of: Critical reviews in oncology/hematology. Volume 152(2020)
• Publication Date: 2020-08
• Subjects: Endometrial cancer -- Targeted therapy -- Immunotherapy -- Immune checkpoint inhibitor -- PARP -- PD-L1 -- PD-1; Oncology -- Periodicals; Hematology -- Periodicals; 616.994
• DOI: 10.1016/j.critrevonc.2020.102973
• Languages: English
• ISSNs: 1040-8428

Abstract

Graphical abstract: Highlights: Effective treatment options for metastatic/recurrent endometrial cancer are limited. Hypermutated (POLE/MMRd) tumors are particularly susceptible to PD-1/PD-L1 blockers. Homologous recombination deficient tumors may be sensitive to PARP inhibitors. PARP inhibitors and PD-1/PD-L1 checkpoint inhibitors may synergize. Three ongoing trials are investigating this combination in endometrial cancer. Abstract: The prognosis of recurrent or metastatic endometrial cancer is poor, with five-year survival of only 10–20 %. First-line therapy consists of either platinum-based chemotherapy or hormonal therapy. No standard subsequent-line therapy has been identified. In recent years, significant progress has been made in the knowledge on underlying molecular biology of endometrial cancer and potential targets for therapy have been identified. Targeted therapies as poly (ADP-ribose) polymerase (PARP) inhibitors and immunotherapy as PD-1/PD-L1 checkpoint inhibitors have the potential to be effective against specific subtypes of endometrial cancer. Preclinical studies have shown that combining these agents may result in a synergistic effect. In this review, we focus on the molecular basis of checkpoint inhibition and targeted therapy as PARP inhibition in endometrial cancer and summarize available clinical data, and ongoing and planned clinical trials that investigate these agents as mono- or combination therapies in endometrial cancer and where relevant, other gynecological cancers.