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Review
March 31, 2021

Clinical Trials of Systemic Chemotherapy for Resectable Pancreatic Cancer: A Review

Author Affiliations
  • 1Department of Surgery, University of Arkansas for Medical Sciences, Little Rock
  • 2Department of Surgery, Duke University Medical Center, Durham, North Carolina
  • 3Department of Surgery, University of Toronto, Toronto, Ontario, Canada
  • 4Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
  • 5Department of Surgery, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
  • 6Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston
  • 7Division of Gastrointestinal Medical Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
  • 8Department of Medicine, Weill Cornell Medical College, New York, New York
  • 9Department of Surgery, The Ohio State University Wexner Medical Center, Columbus
  • 10Deputy Editor, JAMA Surgery
JAMA Surg. Published online March 31, 2021. doi:10.1001/jamasurg.2021.0149
Abstract

Importance  Adjuvant chemotherapy is the standard of care for resected pancreatic ductal adenocarcinoma (PDAC) based on level 1 evidence, but some studies suggest that a neoadjuvant approach (which is standard for borderline resectable PDAC) may be preferable for upfront resectable PDAC. An in-depth review was conducted of all randomized clinical trials that investigated neoadjuvant and adjuvant treatment of patients with resectable or resected PDAC, focusing on trial design, characteristics of enrolled population, and long-term outcomes.

Observations  The existing resectable PDAC trials have good internal validity but variable applicability because of their restrictive eligibility criteria. In these trials, overall survival is the criterion standard end point, but disease-free survival is more feasible, proximate, and specific to the assigned intervention (at the cost of subjective outcome assessment) and thus an acceptable end point in certain contexts. The prolonged survival in the PRODIGE 24 trial highlights both the success of mFOLFIRINOX (modified fluorouracil, leucovorin, irinotecan, and oxaliplatin) and the importance of patient selection. Neoadjuvant and perioperative trials have shown promising preliminary results; however, the number of patients who are not subsequently eligible for surgery reflects the limitations of this approach. Head-to-head comparisons of neoadjuvant and adjuvant treatments are limited to date in Western countries. Precision oncology with genomic and somatic testing for actionable mutations has promising preliminary results and may refine the management of PDAC, although the implications for early-stage disease and neoadjuvant therapy are unknown.

Conclusions and Relevance  This review found that adjuvant chemotherapy with mFOLFIRINOX is currently the standard of care in fit patients with resected PDAC; however, the role of neoadjuvant treatment is expanding. Precision oncology may help individualize the treatment regimen and sequence and improve outcomes. Enrollment of patients with resectable PDAC in clinical trials is strongly encouraged.

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