Background
Phase II RCT included 147 (102 eligible) patients with resectable pancreatic adenocarcinoma randomized to perioperative chemotherapy. Neoadjuvant/adjuvant setting.
Interventions and follow up
Arm A: mFOLFIRINOX (oxaliplatin 85 mg/m², irinotecan 180 mg/m², 5-FU 2400 mg/m² over 46h, q14d) x6 cycles neoadjuvant + 6 cycles adjuvant
Arm B: Gemcitabine 1000 mg/m² + nab-paclitaxel 125 mg/m² D1,8,15 q28d x3 cycles neoadjuvant + 3 cycles adjuvant
Primary endpoint: 2-year OS per arm (vs 40% historical threshold)
mFollow up: NR
Arm B: Gemcitabine 1000 mg/m² + nab-paclitaxel 125 mg/m² D1,8,15 q28d x3 cycles neoadjuvant + 3 cycles adjuvant
Primary endpoint: 2-year OS per arm (vs 40% historical threshold)
mFollow up: NR
Results
2-year OS, arm A: 47% (95% CI 31%-61%; P=.15 vs threshold)
2-year OS, arm B: 48% (95% CI 31%-63%; P=.14 vs threshold)
Outcome: Neither arm exceeded the prespecified 40% threshold
2-year OS, arm B: 48% (95% CI 31%-63%; P=.14 vs threshold)
Outcome: Neither arm exceeded the prespecified 40% threshold
Adverse events
Neoadjuvant (grade ≥3, A vs B): diarrhea 11% vs 4%, neutropenia 19% vs 27%
Adjuvant (grade ≥3, A vs B): neutropenia 0% vs 27%, neuropathy 16% vs 4%
Treatment delivery: resection 73% vs 70%; all treatment completed 49% vs 40%
Adjuvant (grade ≥3, A vs B): neutropenia 0% vs 27%, neuropathy 16% vs 4%
Treatment delivery: resection 73% vs 70%; all treatment completed 49% vs 40%
Conclusions
Neither perioperative mFOLFIRINOX nor gemcitabine/nab-paclitaxel met the prespecified 2-year survival threshold versus historical control in resectable pancreatic cancer; neither was selected for phase III testing.
Key Limitations
Pick-the-winner phase II design with comparison to historical, not concurrent surgery-first control. Modest sample size; not powered for direct head-to-head comparison. Optimal perioperative regimen for resectable disease remains undefined.
Clinical Context
Adjuvant mFOLFIRINOX remains a standard for resected pancreatic cancer (PRODIGE 24/CCTG PA.6). The role of neoadjuvant therapy for clearly resectable disease is still investigational; ESMO supports upfront surgery with adjuvant chemotherapy in this setting.