2615 Background: Alterations in the DNA mismatch repair pathway increase susceptibility to immune checkpoint inhibition (ICI). Tumors with BRCA-related DNA repair defects may have increased antigenicity, which could drive response to ICI. Responses to ICI in ovarian cancer (OC) have been modest. We seek to evaluate the association of BRCA mutations with response to ICI and survival in recurrent OC. Methods: A single-center, retrospective review identified 103 women with recurrent OC and known BRCA mutation status (90 germline and 33 somatic testing) who received ICI between 1/2013-7/2018 (98 on study). Clinical characteristics and duration of ICI (Long > = 24 vs. Short < 24 weeks) were compared by BRCA status. Kaplan Meier survival analysis was used to calculate progression-free (PFS) and overall survival (OS) from start of ICI, and CoxPH models/logrank test were used to assess survival differences by BRCA status. Results: Deleterious germline (g) or somatic (s) BRCA 1/2 mutations were present in 29 (28%) women (12 g BRCA1, 9 g BRCA2, 3 s BRCA1, 5 s BRCA2, 1 g BRCA1/s BRCA1, 3 g BRCA2/s BRCA2, and 1 g BRCA2/s BRCA1). Patients (pts) with BRCA mutations had more lines of treatment prior to ICI (median 5 vs. 4, p = 0.03) and a longer time from diagnosis to ICI (median 54 vs. 38.5 months (mo), p = 0.01), but there were no significant differences in other variables including histology (86% high grade serous), stage at diagnosis (96% Stage III/IV), and platinum status (83% resistant), p > 0.05. Four pts (15%) with BRCA mutations had long duration of ICI as compared with 20 pts (27%) in those without mutations, p = 0.20. Median PFS was 2.2 mo (95% CI 1.7-2.7) in those with BRCA mutations and 3.4 mo (95% CI 2.1-4.0) in those without mutations, HR 1.22 (95% CI 0.78-1.91, p = 0.38). At a median follow-up of 23.3 mo, median OS was 21.3 mo (95% CI 13.7-31.8) in those with BRCA mutations and 19.8 mo (95% CI 13.8-25.3) in those without. This was not significantly different, HR 1.00 (95% CI 0.54-1.87, p = 0.99), after adjustment for prior lines and time from diagnosis to ICI. Conclusions: In our study of heavily pretreated OC pts receiving ICI, BRCA 1/2 mutations were not associated with improved response or survival. These findings should be validated in larger studies.
Immune Stroma in Lung Cancer and Idiopathic Pulmonary Fibrosis: A Common Biologic Landscape?
