As reported in The Lancet by Reni et al, analysis of the first randomization in an Italian 2 × 2 factorial phase III trial (PACT-21 CASSANDRA) has shown better event-free survival with preoperative PAXG (cisplatin, nab-paclitaxel, capecitabine, gemcitabine) vs mFOLFIRINOX (modified fluorouracil, leucovorin, irinotecan, oxaliplatin) in patients with stage I to III resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC).
Study Details
In the open-label multicenter trial, 260 patients were randomly assigned between November 2020 and April 2024 to receive preoperative PAXG (capecitabine at 625 mg/m² twice daily, cisplatin at 30 mg/m², nab-paclitaxel at 150 mg/m², and gemcitabine at 800 mg/m² every 14 days; n = 132) or mFOLFIRINOX (fluorouracil at 2,400 mg/m², leucovorin at 400 mg/m², irinotecan at 150 mg/m², and oxaliplatin at 85 mg/m² every 14 days; n = 128) for 4 months. This was followed by a second randomization to 2 months of additional chemotherapy either before or after surgery. The primary endpoint was event-free survival in the intention-to-treat population. The current report provides findings according to the first randomization.
Key Findings
After a median follow-up of 28.5 months (interquartile range = 20.2–38.2 months), median event-free survival was 16.0 months (95% confidence interval [CI] = 12.4–19.8 months) in the PAXG group vs 10.2 months (95% CI = 8.6–13.5 months) in the mFOLFIRINOX group (hazard ratio = 0.63, 95% CI = 0.47–0.84, P = .0018). Rates at 1 and 3 years were 61% vs 45% and 33% vs 13%, respectively.
Grade ≥3 adverse events were observed in 66% of patients in the PAXG group vs 61% of the mFOLFIRINOX group. The most common events included decreased neutrophils (43%), fatigue (9%), nausea (5%), and peripheral neuropathy (5%) in the PAXG group, and decreased neutrophils (29%), fatigue (8%), increased transaminases (8%), and nausea (6%) in the mFOLFIRINOX group.
The investigators concluded: “PAXG significantly improved [event-free survival] compared with mFOLFIRINOX in resectable or borderline resectable PDAC. Preoperative PAXG could be considered a standard option for resectable or borderline resectable PDAC. Accordingly, preoperative PAXG should be considered as the standard comparator group for future trials in this setting.”
Michele Reni, MD, of the Department of Medical Oncology, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy, is the corresponding author for The Lancet article.
Disclosure: The study was funded by MyEverest and Codice Viola. For full disclosures of all study authors, visit thelancet.com.
