Survival benefit for BRCA-associated epithelial ovarian cancer (OC) is not explained by primary platinum sensitivity alone

Abstract

22030 Background: Patients (pts) with BRCA-associated OC appear to have a survival advantage over those with sporadic OC. It is unclear if this is due to a greater platinum sensitivity or a more indolent disease. In order to examine this issue, we investigated platinum sensitivity, DFS and OS in a cohort of stage III-IV ovarian cancer patients with known BRCA mutation status. Methods: We reviewed all stage III-IV non-mucinous ovarian, fallopian tube or primary peritoneal cancer pts who received primary chemotherapy through the Gynecologic Medical Oncology Service at MSKCC between 12/1/1996 and 9/30/2006 and also underwent BRCA mutation testing on one of two prospective follow-up studies conducted by the Clinical Genetics Service. Staging, treatment and follow-up information was obtained by record review. Recurrence was diagnosed by CT scan or rise in CA125. Platinum sensitivity was defined as recurrence at ≥ 6 months after completion of treatment. Impact on time to progression/death was determined by Kaplan-Meier analysis and a Cox proportional-hazards model adjusted for age at diagnosis (< 60, ≥ 60), debulking status (optimal, suboptimal) and platinum sensitivity (sensitive, resistant). Results: BRCA mutation status was available on 111 of 808 stage III-IV pts who received primary platinum based chemotherapy following surgical staging [33 (+), 78(−)]. BRCA (+) pts were younger (56.2 vs 60. 2; p=0.10) and less likely to be optimally debulked (55% vs 64%; p=0.40). 29 of 33 (88%) BRCA (+) and 62 of 78 (82%) BRCA (−) pts had platinum sensitive disease (p=0.58). Median DFS was 27 months in the BRCA (+) patients vs 24 months in the BRCA (−) patients (p=0.49). Median OS in BRCA (−) pts was 67.8 months and was not yet reached in BRCA (+) pts. On multivariate analysis, OS independently correlated with both platinum sensitivity (HR=0.16, 95% CI: 0.07-0.38) and BRCA (+) mutation status (HR=0.30; 95% CI; 0.10-0.88). Conclusion: In this cohort, we demonstrated that both platinum sensitivity and BRCA mutation status were independently associated with OS. These results suggest that additional factors, including possible differences in tumor biology, may account for some of the differential outcome seen between hereditary and sporadic ovarian cancer. No significant financial relationships to disclose.