Phase II randomized multicenter trial | SWOG Cooperative Group | Resectable PDAC | JAMA Oncology 2021 **Sohal et al.** Davendra P. S. Sohal Published in JAMA Oncology, 2021 [PubMed Link](https://pmc.ncbi.nlm.nih.gov/articles/PMC7821078/) --- ### Essential Takeaway SWOG S1505 demonstrated feasibility of perioperative multi-agent chemotherapy in resectable PDAC using either mFOLFIRINOX or gemcitabine/nab-paclitaxel. Although neither regimen achieved the predefined 2-year OS target, the study supported the practicality of perioperative systemic therapy and accelerated broader adoption of neoadjuvant treatment paradigms. --- ### Clinical Question Can modern perioperative chemotherapy regimens be safely and effectively delivered in resectable PDAC, and is either regimen promising for further development? --- ### Population - Resectable PDAC - ECOG 0–1 - No metastatic disease Central radiographic review was performed to confirm resectability. --- ### Study Design #### Arm 1 — Perioperative mFOLFIRINOX - 3 months neoadjuvant mFOLFIRINOX - Surgery - 3 months adjuvant mFOLFIRINOX #### Arm 2 — Perioperative Gemcitabine/Nab-Paclitaxel - 3 months neoadjuvant gemcitabine/nab-paclitaxel - Surgery - 3 months adjuvant gemcitabine/nab-paclitaxel --- ### Endpoints #### Primary Endpoint 2-year overall survival (OS) #### Secondary Endpoints - Resection rate - R0 resection rate - Pathologic response - Toxicity/adverse events - Treatment completion rates --- ### Key Results #### Overall Survival Neither regimen achieved the predefined 2-year OS target of 58%. Median OS: - mFOLFIRINOX: - 23.2 months - Gemcitabine/nab-paclitaxel: - 23.6 months No meaningful efficacy difference was observed between regimens. --- #### Surgical Outcomes - High rates of surgical resection were achieved in both groups - Favorable R0 resection rates were observed following perioperative therapy These findings demonstrated feasibility of delivering surgery after modern neoadjuvant chemotherapy. --- #### Treatment Completion A substantial proportion of patients were unable to complete all planned perioperative therapy, highlighting logistical and physiologic challenges of prolonged multimodality treatment. --- ### Toxicity Both regimens demonstrated expected multi-agent chemotherapy toxicities, including: - neutropenia - fatigue - gastrointestinal adverse events Overall tolerability was considered acceptable in appropriately selected patients. --- ### Additional Findings #### Supported Perioperative Therapy Concepts SWOG S1505 helped demonstrate that: - preoperative chemotherapy - surgery - postoperative chemotherapy could be successfully integrated in resectable PDAC. #### Reinforced Systemic-First Thinking The study contributed to growing interest in: - biologic selection - early systemic disease control - improved delivery of multi-agent therapy through perioperative treatment paradigms. --- ### Interpretation SWOG S1505 became an important transitional perioperative PDAC trial because it prospectively evaluated modern systemic regimens within a structured perioperative framework. Although neither arm met the predefined efficacy target, the study reinforced the growing role of systemic-first treatment strategies and helped normalize perioperative therapy concepts in resectable pancreatic cancer. --- ### Important Limitations #### Phase II Design - Not powered for definitive regimen comparison #### No Upfront Surgery Control Arm - Unable to directly compare against traditional surgery-first management #### Treatment Attrition - Many patients were unable to complete full perioperative therapy #### Highly Selected Population - Central resectability review - Fit patients treated at experienced centers --- ### Practice Impact SWOG S1505 supported broader adoption of perioperative systemic therapy strategies in resectable PDAC and reinforced several key principles: - modern chemotherapy can be delivered preoperatively - biologic selection is important - prolonged perioperative treatment remains challenging Although not independently practice-changing, the trial became an important bridge between traditional adjuvant paradigms and modern neoadjuvant/perioperative strategies.