Correlation of HRD status with clinical and survival outcomes in patients with advanced-stage ovarian cancer.

Abstract

5568 Background: Nearly 50% of patients with high grade ovarian cancer (HGOC) harbor a germline or somatic mutation in BRCA1/BRCA2 or have tumors characterized by homologous recombination deficiency (HRD). HRD is associated with response to poly(ADP-ribose) polymerase inhibitors (PARPi) in HGOC. Although PARPi show great promise, there is interest in investigating how HRD status affects outcomes and can be used to objectively tailor other treatment strategies. We aimed to compare clinical and survival outcomes in HGOC stratified by HRD status. Methods: We performed a retrospective analysis of all advanced HGOC from April 2013 to June 2019. Patients were included if germline BRCA and HRD status was known. Clinical outcomes were analyzed and stratified by (1) germline BRCA+ (2) germline BRCA - and somatic BRCA/HRD+, or (3) BRCA-/HRD-. Progression free (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods stratified by HRD status and modeled via Cox proportional hazards regression. Results: 1271 patients with advanced HGOC presented during the study period of which 187 met inclusion criteria. 106 patients had germline BRCA mutation, 26 somatic BRCA/HRD+, and 55 BRCA/HRD-. Patients who had HRD- tumor had older median age at diagnosis (63 vs. 54 and 60 years, p<0.001), white race (89% vs. 74% and 68%), non-serous histology (20% vs. 6% and 0%, p=0.04), required more NACT chemotherapy cycles (4 vs. 3 and 3 cycles, p=0.03), and less complete gross resection (R0) at tumor reductive surgery (TRS) (60% vs. 83% and 77%, p=0.02). Patients who had BRCA/HRD- tumor had worse PFS (14.9 months) compared to germline BRCA+ (23.5 months) or somatic BRCA/HRD+ (20.2 months, p<0.001). Patients with BRCA/HRD- disease also had worse OS (42.3 months) compared to germline BRCA+ (68.8 months) or somatic BRCA/HRD+ (69.2 months). Multivariate analysis for PFS revealed that age (HR 1.02, 95% CI 1.00-1.04), p=0.01), stage (HR 5.7, 95% CI 1.39-23.4, p=0.02), R0 resection at TRS (HR 0.41, 95% CI 0.21-0.83, p=0.01), and BRCA/HRD- status (HR 1.63, 95% CI 1.07-2.48, p=0.02) were significant factors impacting PFS. Multivariate analysis for OS revealed that age (HR 1.07, 95% CI 1.03-1.10, p<0.001) and R0 resection at TRS (HR 0.19, 95% CI 0.08-0.44, p<0.001) were significant factors impacting OS. Conclusions: Germline BRCA-mutant, somatic BRCA/HRD+ HGOC was associated with improved PFS and OS regardless of primary TRS or NACT. BRCA-/HRD- was a negative prognostic factor for survival in HGOC.