TOPLINE:

Preoperative cisplatin, nab-paclitaxel, capecitabine, and gemcitabine (PAXG) prolonged event-free survival compared to modified fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX) in patients with resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC).

METHODOLOGY:

• Researchers conducted a randomised, open-label, factorial phase 3 trial including 261 patients with resectable or borderline resectable PDAC across 17 Italian academic hospitals.
• Patients were randomly assigned to receive either PAXG (capecitabine 1250 mg/m²
  daily and cisplatin 30 mg/m², nab-paclitaxel 150 mg/m², and gemcitabine 800 mg/m² every 14 days; n = 132; median age, 65 years; 48% men) or mFOLFIRINOX (fluorouracil 2400 mg/m², leucovorin 400 mg/m², irinotecan 150 mg/m², and oxaliplatin 85 mg/m² every 14 days; n = 128; median age, 63 years; 52% men) within 7 days of randomisation.
• Surgical resection was scheduled 4-8 weeks after completing intravenous chemotherapy, following standard clinical practice.
• The primary endpoint was event-free survival, and secondary endpoints included rates of radiologic response, carbohydrate antigen 19-9 (CA19-9) response, resection rates, pathologic outcomes, chemotherapy toxicity, quality of life, and overall survival.

TAKEAWAY:

• Treatment with PAXG extended median event-free survival to 16.0 months compared to 10.2 months for treatment with mFOLFIRINOX (hazard ratio, 0.63; P
  = .0018).
• The PAXG group showed higher rates of disease control (98% vs 91%; P = .0088), CA19-9 response (88% vs 64%; P < .0001), and pathologic stage < II (35% vs 23%; P = .030).
• At least one grade 3 or worse adverse event occurred in 66% of patients in the PAXG group and 61% of those in the mFOLFIRINOX group, which included one fatal event.
• Quality-of-life assessment showed clinically meaningful deterioration in fewer domains with PAXG vs mFOLFIRINOX, especially in scores for nausea and vomiting (P = .057).
• Preliminary results showed a median survival of 32.1 months in the PAXG group and 26.4 months in the mFOLFIRINOX group. The 2-year and 3-year overall survival rates were 66% and 48% in the PAXG group and 58% and 41% in the mFOLFIRINOX group, respectively.

IN PRACTICE:

"Preoperative PAXG could be considered a standard option for resectable or borderline resectable PDAC," the authors wrote.

SOURCE:

This study was led by Michele Reni, MD, Department of Medical Oncology, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy. It was published online on November 20, 2025, in The Lancet.

LIMITATIONS:

The choice and definition of event-free survival as the primary endpoint could be considered a limitation, although disease-free survival has been previously accepted as a reliable surrogate endpoint for overall survival in pancreatic cancer trials. The use of CA19-9 increases as an event criterion was not based on available evidence. The external validity of the study may be limited by its focus on high-volume academic centres and the upper age limit of 75 years.

DISCLOSURES:

This study was funded by MyEverest and Codice Viola. Several authors reported receiving honoraria, consulting fees, or travel expenses or having other ties with various sources. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.