Background
Prospective phase II RCT (AIO pancreatic cancer group) of 126 patients with resectable pancreatic ductal adenocarcinoma (cT1-3) without distant metastases and no prior tumor-specific treatment. Resectability was defined by clear fat planes around the celiac, hepatic, and superior mesenteric arteries.
Interventions and follow up
Arm A (perioperative): 2 pre-operative + 4 post-operative cycles of gemcitabine 1000 mg/m2 + nab-paclitaxel 125 mg/m2 on days 1, 8, 15 Q28D
Arm B (adjuvant): 6 cycles of adjuvant gemcitabine 1000 mg/m2 + nab-paclitaxel 125 mg/m2 on days 1, 8, 15 Q28D
Primary endpoint: DFS at 18 mo (modified ITT)
mFollow up: Approximately 18 mo
Arm B (adjuvant): 6 cycles of adjuvant gemcitabine 1000 mg/m2 + nab-paclitaxel 125 mg/m2 on days 1, 8, 15 Q28D
Primary endpoint: DFS at 18 mo (modified ITT)
mFollow up: Approximately 18 mo
Results
18-mo DFS rate (mITT): 33.3% (Arm A) vs 41.4% (Arm B); prespecified target of 55% not reached in either arm
mDFS (ITT): 11.5 mo (Arm A) vs 5.9 mo (Arm B)
mOS (ITT): 25.5 mo (Arm A) vs 16.7 mo (Arm B)
Treatment exposure: 90% in Arm A completed pre-operative chemotherapy; 58% in Arm B started adjuvant chemotherapy
mDFS (ITT): 11.5 mo (Arm A) vs 5.9 mo (Arm B)
mOS (ITT): 25.5 mo (Arm A) vs 16.7 mo (Arm B)
Treatment exposure: 90% in Arm A completed pre-operative chemotherapy; 58% in Arm B started adjuvant chemotherapy
Adverse events
Hematologic (grade 3-4, A vs B): Neutropenia 21.1% vs 12.3%; anemia 10.5% vs 1.8%
Constitutional (grade 3-4, A vs B): Fatigue 8.8% vs 5.3%
Constitutional (grade 3-4, A vs B): Fatigue 8.8% vs 5.3%
Conclusions
Perioperative gemcitabine/nab-paclitaxel was well tolerated, with encouraging mOS in the perioperative arm. The primary 18-mo DFS target of 55% was not reached in either arm; DFS numerically favored the adjuvant arm while OS numerically favored the perioperative arm, with greater chemotherapy exposure in the perioperative group. Neoadjuvant/perioperative therapy warrants further prospective study in resectable PDAC.
Key Limitations
Phase II, modest sample size; primary endpoint not met; not powered for definitive OS comparison; gemcitabine/nab-paclitaxel backbone rather than FOLFIRINOX; high attrition before adjuvant therapy in Arm B.
Clinical Context
NEONAX is hypothesis-generating; it did not establish perioperative chemotherapy as a new standard for clearly resectable PDAC. Adjuvant mFOLFIRINOX (PRODIGE-24) remains the preferred adjuvant standard for fit patients; ESMO guidelines reserve neoadjuvant therapy chiefly for borderline-resectable disease pending further randomized data.