Phase II randomized multicenter trial | AIO/Pancreatic Cancer Group | Resectable PDAC | Annals of Oncology 2023 **Seufferlein et al.** Thomas Seufferlein Published in Annals of Oncology, 2023 [PubMed Link](https://pubmed.ncbi.nlm.nih.gov/36209981/) --- ### Essential Takeaway NEONAX compared perioperative versus adjuvant-only gemcitabine/nab-paclitaxel in resectable PDAC. Although the predefined DFS benchmark was not reached in either arm, perioperative therapy improved chemotherapy delivery, increased R0 resection rates, and numerically improved overall survival, supporting growing interest in systemic-first treatment strategies. --- ### Clinical Question In resectable PDAC, does perioperative gemcitabine/nab-paclitaxel improve outcomes compared with an adjuvant-only strategy? --- ### Population - Resectable PDAC - NCCN resectability criteria - ECOG 0–1 - No metastatic disease 127 patients enrolled across 22 German centers. --- ### Study Design #### Arm A — Perioperative Gemcitabine/Nab-Paclitaxel - 2 cycles neoadjuvant gemcitabine/nab-paclitaxel - Surgery - 4 cycles adjuvant gemcitabine/nab-paclitaxel #### Arm B — Adjuvant Gemcitabine/Nab-Paclitaxel - Upfront surgery - 6 cycles adjuvant gemcitabine/nab-paclitaxel --- ### Endpoints #### Primary Endpoint Disease-free survival (DFS) rate at 18 months in the modified intention-to-treat population. Predefined success threshold: - DFS rate ≥55% #### Secondary Endpoints - Overall survival (OS) - Median DFS - R0 resection rate - Chemotherapy completion - Toxicity/adverse events --- ### Key Results #### Primary Endpoint The predefined DFS benchmark was not reached in either arm. 18-month DFS: - Perioperative arm: - 33.3% - Adjuvant-only arm: - 41.4% --- #### Overall Survival Median OS numerically favored perioperative therapy: - 25.5 months vs 16.7 months Although the study was not powered for definitive OS comparison, this finding generated significant interest. --- #### Disease-Free Survival Median DFS numerically favored perioperative therapy: - 11.5 vs 5.9 months --- #### Chemotherapy Delivery A major finding was improved systemic therapy delivery with perioperative treatment. - 90% completed preoperative chemotherapy in Arm A - Only 58% initiated adjuvant chemotherapy in Arm B This reinforced the challenge of delivering intended postoperative therapy after pancreatic resection. --- #### Surgical Outcomes R0 resection rates favored perioperative therapy: - 88% vs 67% Curative-intent surgery remained feasible following neoadjuvant treatment. --- ### Toxicity Treatment was generally safe and well tolerated in both arms. Expected toxicities included: - neutropenia - fatigue - gastrointestinal adverse events - peripheral neuropathy --- ### Interpretation NEONAX became an important modern perioperative PDAC trial because it directly compared perioperative versus adjuvant-only systemic therapy in resectable disease. Although technically negative for its primary endpoint, the study reinforced several increasingly important principles: - postoperative chemotherapy delivery is difficult - systemic therapy before surgery is feasible - perioperative strategies may improve overall treatment exposure - biologic selection before surgery is increasingly valuable The trial also contributed to broader momentum toward neoadjuvant and perioperative treatment paradigms in resectable PDAC. --- ### Important Limitations #### Phase II Design - Not powered for definitive survival conclusions #### Primary Endpoint Negative - DFS benchmark was not achieved in either arm #### Gemcitabine/Nab-Paclitaxel Backbone - Modern practice increasingly favors mFOLFIRINOX in fit patients #### Small Sample Size - Limited statistical power #### Short Neoadjuvant Duration - Only 2 preoperative cycles administered --- ### Practice Impact NEONAX supported growing interest in perioperative systemic therapy strategies for resectable PDAC and reinforced the importance of treatment delivery before surgery whenever feasible. The study became part of the broader evidence base supporting: - systemic-first treatment approaches - biologic selection prior to surgery - neoadjuvant/perioperative management paradigms in modern pancreatic cancer care.