Neoadjuvant therapy in patients with pancreatic ductal adenocarcinoma (PDAC) with germline DNA damage repair (DDR) mutations: A dual institution retrospective study.

• DOI: 10.1200/jco.2024.42.16_suppl.4164
• Publication Date: 2024-06-21T17:57:17Z
• Authors: Murtaza Ahmed; Marco Ventin; Giulia Cattaneo; Arya Shahrzad; Anser Ali Abbas; Brent K Larson; John Davelaar; Simon K. Lo; Matthew Ebia; Ashley Wachsman; Srinivas Gaddam; Jun Gong; Nicholas Nissen; Kambiz Kosari; Alexandra Gangi; Andrew Eugene Hen...; Cristina R. Ferrone; Arsen Osipov
• Keywords: Neoadjuvant Therapy; DNA Damage Repair

4164 Background: Neoadjuvant approaches are routinely used in the treatment of resectable, borderline resectable (BR) and locally advanced (LA) PDAC. However, there few predictive biomarkers response to neoadjuvant therapy potentially PDAC patients. Mutations DDR genes occur frequently PDAC; however, their implications setting remain unclear. Methods: We conducted a dual center (Cedars-Sinai MGH), matched cohort retrospective analysis patients with BR or LA without mutations ( ATM, BARD1, BRCA1, BRCA2, CHEK2, CDKN2A, MLH1, MSH2, MSH3, MSH6, MUTYH, NTHL1, PALB2, PMS2, STK11, TP53) who received therapy. The Fisher’s exact test Chi square was for categorical variables long-rank disease-free survival (DFS) overall (OS). Results: A total 104 were included, which 52 had pathogenic germline mutation gene (DDR-positive) no (DDR-negative). Median age 63 years, 53% (n=55) male, 93% (n=97) FOLFIRINOX as first-line At diagnosis, 24% (n=25) stage, 39% (n=41) stage 37% (n=38) stage. Between two groups, difference median age, sex, regimen (all p≥0.4). rate surgical resection 73% DDR-positive group vs. 71% DDR-negative p>0.99). When classified by between rates, respectively, 100% 92% p=0.29) patients, 95% 90% p=0.58) 32% p=0.73) Only 4 all DDR-positive, achieved complete pathologic response. near 47.2% (n=17) 25.7% (n=9) p=0.06). DFS not reached 10.8 months (HR 0.37; p = 0.002). OS 88.3 41.3 0.55; p=0.04). For resected 57.1 0.45; p=0.048). non-resected 25.3 15.2 0.51; p=0.09). Conclusions: This study demonstrated that LA-PDAC have significantly prolonged increased rates. suggests benefit from across mutations.