Dr Reni on the Efficacy of Preoperative PAXG in Stage I to III PDAC

"What we observed is that the PAXG regimen significantly prolonged EFS, both from a statistical and clinical perspective. In particular, the median EFS was prolonged…from 10.2 to 16.0 months, and the 3-year EFS [rate] was more than doubled, from 13% to 31% in the mFOLFIRINOX and PAXG arms, respectively."

Michele Reni, MD, a specialist in medical oncology in the Department of Medical Oncology at San Raffaele Scientific Institute, discussed findings from the phase 3 CASSANDRA trial (NCT04793932) evaluating the efficacy of preoperative PAXG (capecitabine, cisplatin, nab-paclitaxel [Abraxane], and gemcitabine) compared with mFOLFIRINOX (oxaliplatin, leucovorin, irinotecan, and fluorouracil) in patients with resectable or borderline resectable stage I to III pancreatic ductal adenocarcinoma.

Results from the trial presented at the 2025 ASCO Annual Meeting demonstrated that At a median follow-up of 24.5 months in the PAXG arm and 26.0 months in the mFOLFIRINOX arm, the median event-free survival (EFS) was 16.0 months (95% CI, 12.4-19.8) with PAXG vs 10.2 months (95% CI, 8.7-13.0) with mFOLFIRINOX (HR, 0.64; 95% CI, 0.48-0.86; P = .003). The respective 1-year EFS rates were 61% (95% CI, 56%-65%) vs 45% (95% CI, 41%-49%), and the 3-year EFS rates were 31% (95% CI, 25%-36%) vs 13% (95% CI, 9%-17%) in the respective arms.

According to Reni, these findings support the clinical relevance of the PAXG regimen in the neoadjuvant setting, particularly given the observed 6-month increase in median EFS and the more than twofold increase in 3-year EFS. He emphasized that the improvement in multiple clinical endpoints suggests a potential benefit in overall treatment durability and long-term disease control.

Ultimately, Reni stated that PAXG may represent the most suitable neoadjuvant option for patients with resectable or borderline resectable stage I to III pancreatic ductal adenocarcinoma. Further investigation may help confirm these findings and support broader incorporation of PAXG into standard treatment strategies for early-stage disease.