Phase II multicenter randomized trial | PRODIGE Investigators | Resectable PDAC | European Journal of Cancer 2022 **Dahan et al.** Laurent Dahan Published in European Journal of Cancer, 2022 [PubMed Link](https://pubmed.ncbi.nlm.nih.gov/35714672/) --- ### Essential Takeaway PANACHE01-PRODIGE48 evaluated perioperative chemotherapy strategies in resectable PDAC using either mFOLFIRINOX or FOLFOX compared with upfront surgery. The trial demonstrated feasibility of perioperative treatment approaches and suggested improved treatment completion with neoadjuvant strategies, further supporting movement toward systemic-first management in resectable pancreatic cancer. --- ### Clinical Question Can perioperative chemotherapy strategies improve feasibility and treatment delivery compared with upfront surgery in resectable PDAC? --- ### Population - Resectable PDAC - ECOG 0–1 - No metastatic disease Patients were considered candidates for curative-intent pancreatic resection. --- ### Study Design #### Arm 1 — Perioperative mFOLFIRINOX - 4 cycles neoadjuvant mFOLFIRINOX - Surgery - 8 cycles adjuvant mFOLFIRINOX #### Arm 2 — Perioperative FOLFOX - 4 cycles neoadjuvant FOLFOX - Surgery - 8 cycles adjuvant FOLFOX #### Arm 3 — Upfront Surgery - Immediate surgery - Adjuvant chemotherapy per investigator choice --- ### Endpoints #### Primary Endpoint Feasibility of completing the full therapeutic sequence #### Secondary Endpoints - Overall survival (OS) - Disease-free survival (DFS) - Resection rate - R0 resection rate - Toxicity/adverse events - Treatment completion rates --- ### Key Results #### Feasibility Perioperative strategies demonstrated acceptable feasibility and treatment completion rates. mFOLFIRINOX appeared more promising than FOLFOX in terms of oncologic activity. --- #### Treatment Delivery Preoperative therapy improved the likelihood that patients received intended systemic treatment. The study reinforced persistent challenges associated with delivering prolonged postoperative therapy alone after pancreatic resection. --- #### Surgical Outcomes - Curative-intent resections remained feasible following neoadjuvant therapy - Favorable R0 resection rates were observed in perioperative arms --- ### Toxicity Expected multi-agent chemotherapy toxicities were observed, including: - neutropenia - fatigue - gastrointestinal adverse events mFOLFIRINOX demonstrated greater toxicity but stronger apparent oncologic activity compared with FOLFOX. --- ### Additional Findings #### Supported Perioperative Treatment Paradigms PANACHE01 contributed to growing evidence that: - systemic therapy can be delivered safely before surgery - perioperative strategies may improve chemotherapy exposure - biologic selection before surgery is increasingly important #### Reinforced Preference for mFOLFIRINOX The trial further supported mFOLFIRINOX as the preferred intensified perioperative backbone in fit patients. --- ### Interpretation PANACHE01-PRODIGE48 became an important exploratory perioperative PDAC trial because it prospectively evaluated modern systemic treatment strategies against traditional surgery-first management. Although not powered for definitive survival conclusions, the study reinforced several evolving themes in pancreatic oncology: - perioperative treatment is feasible - treatment delivery matters - systemic-first approaches are increasingly favored in resectable disease The trial also contributed to broader transition away from surgery-first paradigms. --- ### Important Limitations #### Phase II Design - Not powered for definitive survival comparisons #### Relatively Small Sample Size - Limited statistical power #### Exploratory Nature - Primarily designed as a feasibility study #### Evolving Standards - Conducted during rapid evolution of neoadjuvant and perioperative treatment paradigms --- ### Practice Impact PANACHE01-PRODIGE48 supported growing interest in perioperative systemic therapy strategies for resectable PDAC and reinforced feasibility of delivering preoperative chemotherapy. The study contributed to broader acceptance of: - biologic selection before surgery - perioperative chemotherapy approaches - intensified systemic therapy in fit patients Although not independently practice-changing, PANACHE01 became part of the growing body of evidence supporting modern perioperative management strategies in pancreatic cancer.