Clinicopathological features of homologous recombination-deficient epithelial ovarian cancers: sensitivity to PARP inhibitors, platinum, and survival.

Abstract

Up to 50% of epithelial ovarian cancers (EOC) display defects in the homologous recombination (HR) pathway. We sought to determine the ramifications of the homologous recombination-deficient (HRD) status on the clinicopathologic features, chemotherapy response, and survival outcomes of patients with EOCs. HR status was determined in primary cultures from ascitic fluid in 50 chemotherapy-naïve patients by a functional RAD51 immunofluorescence assay and correlated with in vitro sensitivity to the PARP inhibitor (PARPi), rucaparib. All patients went on to receive platinum-based chemotherapy; platinum sensitivity, tumor progression, and overall survival were compared prospectively in HR-competent versus HRD patients. Compared with HR-competent patients, the HRD group was predominantly serous with a higher median CA125 at presentation. HRD was associated with higher ex vivo PARPi sensitivity and clinical platinum sensitivity. Median follow-up duration was 14 months; patients in the HRD group had lower tumor progression rates at 6 months, lower overall/disease-specific death rates at 12 months, and higher median survival. We therefore suggest that HRD as predicted by a functional RAD51 assay correlates with in vitro PARPi sensitivity, clinical platinum sensitivity, and improved survival outcome.

• Authors: Asima Mukhopadhyay, Elizabeth R Plummer, Ahmed Elattar, San Soohoo, Bisha Uzir, Jennifer E Quinn, W Glenn McCluggage, Perry Maxwell, Harriet Aneke, Nicola J Curtin, Richard J Edmondson
• Journal: Cancer research (Cancer Res) Vol. 72 Issue 22 Pg. 5675-82 (Nov 15 2012) ISSN: 1538-7445 [Electronic] United States
• PMID: 23066035 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2012 AACR.

Chemical References

• Enzyme Inhibitors
• Poly(ADP-ribose) Polymerase Inhibitors
• Carboplatin
• Paclitaxel

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carboplatin (administration & dosage)
• Carcinoma, Ovarian Epithelial
• Combined Modality Therapy
• DNA Breaks, Double-Stranded
• Enzyme Inhibitors (administration & dosage)
• Female
• Homologous Recombination
• Humans
• Kaplan-Meier Estimate
• Middle Aged
• Neoplasms, Glandular and Epithelial (drug therapy, genetics, pathology, surgery)
• Ovarian Neoplasms (drug therapy, genetics, pathology, surgery)
• Paclitaxel (administration & dosage)
• Poly(ADP-ribose) Polymerase Inhibitors