Advances in the treatment of platinum resistant epithelial ovarian cancer: an update on standard and experimental therapies

Abstract

ABSTRACT Introduction: Platinum-resistant ovarian cancer (PROC) is broadly defined as disease recurrence within 6 months of completing platinum-based chemotherapy, either in the primary or recurrent setting. Although there is significant heterogeneity, PROC is generally associated with poor outcomes and low response rates to standard chemotherapy. There have been novel developments in therapeutics for PROC based on biomarkers and a more nuanced understanding of DNA repair and immunologic pathways. Areas covered: This review provides a summary of standard of care and experimental therapies for patients with PROC. Recent advances in our understanding of the DNA damage response and immunobiology of ovarian cancer have paved the way for single agent and combinatorial strategies involving PARP inhibitors, cell cycle checkpoint inhibitors, and immune checkpoint inhibitors to overcome PARP resistance, capitalize on high replication stress, and promote effective anti-tumor immunity, respectively. Furthermore, novel agents including antibody drug conjugates, bispecific antibodies, and recombinant fusion proteins show promise as experimental treatment options. Expert opinion: Standard and experimental treatment options available to patients with PROC have expanded. Testing for BRCA status, tumor mutational burden, and mismatch repair deficiency is recommended to guide therapy. Clinical trial participation is strongly encouraged with a focus on biomarker-driven trials targeting specific patient populations. Novel approaches such as ADCs, bispecific antibodies, targeting the GAS6/AXL and Notch pathways, and oncolytic virotherapy show considerable promise as emerging therapies.