Single center retrospective analysis of neoadjuvant therapy in resectable pancreatic adenocarcinoma.

Abstract

e16467 Background: Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers and is expected to become the second leading cause of cancer-related death in the United States by 2030. Only 10-15% of patients are resectable at diagnosis. For those who undergo surgery, five-year survival is close to 20%. Current guidelines recommend surgery followed by adjuvant systemic therapy. Neoadjuvant therapy (NAT) to improve patient outcomes is controversial owing to conflicting evidence. 1 The NorPACT-1 trial, which evaluated resectable PDAC, showed improved median overall survival (mOS) in upfront surgery (US) cohort while subgroup analysis of resectable PDAC cohort in the PREOPANC trial found similar mOS between NAT and US. These findings are contradictory to the Roesel et al 2023 meta-analysis that reported improvements in OS and R0 resections in patient who received NAT. 2,3 Against this backdrop, we conducted a retrospective single-center study to evaluate outcomes from NAT vs. US in resectable PDAC patients. Methods: Data was collected on patients diagnosed with resectable PDAC over a 10-year period (1/1/2015-1/1/2025). Patient characteristics evaluated included age, sex, ECOG performance status, stage at diagnosis, tumor location (e.g., head, body, tail), and mismatch repair (MMR) gene status. Patients who received NAT were evaluated by regimen, number of cycles, delayed or missed cycles, grade ≥3 toxicities, and radiographic response based on RECIST criteria. Those who underwent surgery (i.e., following NAT vs. US) were evaluated for resection status (e.g., R0 vs. R1), adjuvant therapy received, and evidence of progression. Our primary end point was median OS. Secondary endpoints included progression-free survival (PFS) and R0 resection rates. All analysis were performed using SAS software version 9.4. Results: 119 patients met inclusion criteria; 84 received NAT followed by surgery and 35 completed US. Patient demographics between these cohorts were comparable. Median OS (3.38 vs. 3.36 years; HR = 0.86, 95% CI [0.52-1.43]; p = 0.33) and median PFS (1.77 vs. 1.29 years; HR = 0.80, 95% CI [0.50-1.27]; p = 0.35) were similar. R0 resection rates favored US over NAT (89 vs. 85.7%; p = 0.756). Conclusions: Our cohort included resectable PDAC who completed NAT followed by surgery or upfront surgery. We observed no significant difference in mOS or PFS between NAT and US. These results are more closely aligned with the findings of the PREOPANC trial’s subgroup analysis of resectable PDAC rather than the results of the NorPACT-1 trial. Although not statistically significant, R0 resection rates were numerically higher in the upfront surgery cohort, a finding that contrasts with PREOPANC. 2,3 The optimal treatment strategy for patients with resectable PDAC remains an area of active investigation with ongoing trials such as PREOPANC-3 and Alliance A021806 expected to further clarify the role of NAT.