Ovarian Cancer: Distinct Clusters of Chemotherapy Nonresponders Identified

A study presented at the 48th Annual Meeting of the Society of Gynecologic Oncology has identified 3 distinct clusters of patients with serous epithelial ovarian cancer who do not respond to achieve incomplete response to standard chemotherapy.¹

Approximately one-third of patients with serous epithelial ovarian cancer will not respond to initial platinum chemotherapy. Therefore, researchers at University of Iowa Hospitals and Clinics in Iowa City sought to classify nonresponders to initial chemotherapy through genomic and clinical characterization.

Investigators analyzed data from 88 patients with platinum-refractory or platinum-resistant serous ovarian cancer included in The Cancer Genome Atlas with complete biological and clinical information. Biological information evaluated included gene copy number variation, mRNA expression, gene somatic mutations, and DNA promoter methylation, while clinical variables included surgical treatment, microRNA expression, and TP53 mutation.

Investigators identified 3 distinct clusters of patients who did not respond to platinum-based chemotherapy. The first cluster had predominantly stage IV disease, underwent suboptimal debulking, had underexpression of miRNAs and mRNAs, hypomethylated DNA, “loss of function” TP53 mutations, and had overexpression of PDGFR-driven pathways.

In contrast, the second cluster had low miRNA expression, generalized hypermethylation, MUC17 mutations, and significant activation of the WNT/β-catenin pathway. The third cluster had more patients with stage III disease who had more optimal debulking, overexpression of miRNAs, mixed methylation patterns, and “gain of function” TP53 mutations.

However, researchers found that survival was similar between the 3 clusters of chemotherapy nonresponders (P =.48).

The findings suggest that anti-VEGF and tyrosine kinase inhibitors, anti-PD-1 inhibitors, and a combination of proteasome inhibitors and histone deacetylase inhibitors may be potential treatment strategies for clusters 1, 2, and 3, respectively.

Reference

1. McDonald ME, Salinas EA, Newtson AM, Goodheart MJ, Leslie KK, Gonzalez Bosquet J. Cluster analysis of chemotherapy non-responders for patients with serous epithelial ovarian cancer. Paper presented at: 48th Annual Meeting of the Society of Gynecologic Oncology; March 12-15, 2017; National Harbor, MD.