Extending Pre-Operative Chemotherapy May Be Preferable for Resectable and Borderline Resectable Pancreatic Cancer
Key Clinical Takeaways
- Design/Population: In the phase 3 CASSANDRA trial, 170 patients with resectable or borderline resectable pancreatic ductal adenocarcinoma received 4 months of PAXG or mFOLFIRINOX and were then randomized to 2 additional months of chemotherapy before surgery (long-course, n = 88) or immediate surgery (short-course, n = 82).
- Key Outcomes: Median EFS and OS were similar between arms (EFS 13.6 vs 13.0 mo; OS 36.3 vs 32.8 mo; both P > .05), but long-course therapy significantly improved pCR (5% vs 0%; P = .04) and N0 resection rates (44% vs 25%; P = .01).
- Clinical Relevance: Extending pre-operative chemotherapy improved pathologic response and nodal clearance without compromising safety or resection rates, suggesting potential benefit of longer neoadjuvant duration in resectable pancreatic cancer.
Results from the phase 3 CASSANDRA trial demonstrate that extending pre-operative chemotherapy improved pathologic outcomes among patients with resectable or borderline resectable pancreatic ductal adenocarcinoma.
These results were presented by Michele Reni, MD, San Raffaele Research Hospital, Milan, Italy, at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, Germany.
This study randomized 170 patients to receive 4 months of either PAXG (cisplatin plus nab-paclitaxel, capecitabine, and gemcitabine) or mFOLFIRINOX (5-fluorouracil plus leucovorin, irinotecan, and oxaliplatin). Patients without progression or major toxicity were randomized again to continue chemotherapy for 2 additional months prior to surgery (long-course arm, n = 88) or proceed directly to surgery followed by 2 months of post-operative chemotherapy (short-course arm, n = 82). The primary end point was event-free survival (EFS), as calculated from the second randomization. Key secondary end points included overall survival (OS), resection rates, pathological complete response (pCR), N0 resection rates, R0 resection rates, and intra- or early post-operative M+ resection rates in both the intention-to-treat and per protocol populations (per protocol long-course arm, n = 79; per protocol short-course arm, n = 77).
In the intention-to-treat population, median EFS was 13.6 months in the long-course arm and 13 months in short-course arm (P = .94) with 3-year EFS rates of 29% and 23%, respectively (P = .94). Median OS was 36.3 months in the long-course arm and 32.8 months in the short-course arm with 3-year OS rates of 54% and 44%, respectively (P = .89). Resection rates were 78% in the long-course arm and 84% in the short-course arm (P = .34) and pCR rates were 5% and 0%, respectively (P = .04). N0 resection rate was 44% in the long-course arm and 25% in the short-course arm (P = .01). R0 resection rate was 60% in the long-course arm and 56% in the short-course arm (P = .59). Intra- or early post-operative M+ resection rates were 12% and 10%, respectively (P = .57).
In the per protocol population, median EFS was 15.5 months in the long-course arm and 15.2 months in the short-course arm with 3-year EFS rates of 32% and 24%, respectively (P = .69). Median OS was 50.4 months in the long-course arm and 32.8 months in the short-course arm with 3-year OS rates of 54% and 44% (P = .42). Resection rates were 80% in the long-course arm and 86% in the short-course arm (P = .28) and pCR rates were 4% and 1%, respectively (P =.30). N0 resection rate was 44% in the long-course arm and 26% in the short-course arm (P = .01). R0 resection rate was 61% in the long-course arm and 56% in the short-course arm (P = .50). Intra- or early post-operative M+ resection rates were 12% in both treatment arms (P = .96).
“Longer pre-operative [chemotherapy] significantly increased pCR and N0 resection rate in [resectable or borderline resectable pancreatic ductal adenocarcinoma], concluded Dr Reni et al. Though “EFS was not significantly prolonged […] data suggests that longer duration may be preferable.”
Source:
Reni M, Orsi G, Macchini M, et al. Results of a randomized phase III trial of short-course versus long-course pre-operative chemotherapy for stage I-III pancreatic ductal adenocarcinoma (PDAC). Presented at the 2025 ESMO Congress. October 17-21, 2025; Berlin, Germany. LBA85
