Abstract B29: Outcomes of DNA repair-deficient pancreatic cancers: KU Cancer Center experience

Abstract

Abstract Background: DNA repair-defective pancreatic cancers are a subset that could be exploited therapeutically. BRCA 1 and 2 deficient pancreatic cancers have shown improved survival outcomes with platinum-based chemotherapy and/or PARP inhibitors. However, survival outcomes of pancreatic cancers harboring other DNA repair defects are not well understood. Methods: We retrospectively evaluated survival outcomes of 60 metastatic pancreatic cancer patients who had their tumors profiled by standard-of-care next-generation sequencing. Patients with deficient DNA repair genes such as BRCA1 (n=2), BRCA2 (n=12), ATM (n=7), PALB2 (n=1), NBN (n=1), and BRIP1 (n=1) were grouped into DNA repair-deficient group. The remaining patients were grouped into DNA repair-proficient group. Comparative survival analysis between the two groups was performed using Kaplan-Meir methods. Results: Demographic/baseline data for the DNA repair-deficient group (n=22) vs. the proficient group (n=38) are compared as follows: 12 vs. 20 males, 10 vs. 18 females, 20 vs. 33 with ECOG scores 0-1, 1 vs. 4 with a ECOG score 2+, 12 vs. 19 with tumors in the head, 7 vs. 6 with tumors in the body, 4 vs. 12 with tumors in the tail, 4 vs. 10 with a CA 19-9 of <34, 12 vs. 24 with a CA 19-9 of >34, 7 vs. 19 received initial gemcitabine-based therapy, and 15 vs. 19 received initial FOLFIRINOX chemotherapy. Survival analysis in DNA repair-deficient vs. proficient group revealed comparable median PFS of 7 months (95%CI 5-32 months) vs. 7 months (95% CI 4-30 months) [HR 0.97, p=0.9] but a longer median OS of 18 months vs. 12 months [HR 0.51, p=0.07]. Among DNA repair-deficient group, median OS was 12 months for patients who received first-line platinum-based chemo (n=15) vs. 5 months for first-line non-platinum chemo (n=7) [HR 0.57, p=0.39]. Conclusion: In addition to BRCA1/2 deficiency, pancreatic cancers that harbor other DNA repair defects also show trend towards improved OS when compared to DNA repair-proficient cancers. Treatment with first-line platinum-based chemo favored better OS in DNA repair-deficient cancers. Though median PFS appears comparable, the upper limit of 95% CI for PFS is higher for the DNA repair-deficient cancers. These findings did not meet statistical significance given our small sample size and need to be validated in a larger cohort. We currently have an ongoing clinical trial to investigate DNA repair defects in addition to BRCA1/2 in pancreatic cancers (NCT03553004). Citation Format: Anup Kasi, Suhaib Bajwa, Mohammed Al-Jumayli, Anwaar Saeed, Andrew Godwin. Outcomes of DNA repair-deficient pancreatic cancers: KU Cancer Center experience [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B29.