Postoperative Adverse Events Following Neoadjuvant Therapy and Surgery for Borderline Resectable Pancreatic Cancer in a Phase 2 Clinical Trial (Alliance A021501)

Ann Surg Oncol. 2024 Oct;31(10):7033-7042. doi: 10.1245/s10434-024-15670-6. Epub 2024 Jul 15.

Abstract

Background: Postoperative adverse events (AEs) in patients with borderline resectable pancreatic ductal adenocarcinoma (BR-PC) treated with neoadjuvant therapy and pancreatectomy in the national cooperative group setting have not been previously characterized. We conducted a preplanned secondary analysis of patients enrolled on the Alliance A021501 clinical trial to quantify perioperative AE rates.

Methods: The A021501 phase 2 trial randomized patients with BR-PC to receive 8 doses of mFOLFIRINOX (Arm 1) or 7 doses of mFOLFIRINOX and hypofractionated radiotherapy (Arm 2), followed by pancreatectomy (December 31, 2016 to May 31, 2019). Adverse events were assessed 90 days after pancreatectomy.

Results: Of 126 enrolled patients, 51 (40%) underwent pancreatectomy (n = 32, Arm 1; n = 19, Arm 2) at 28 institutions. Five (10%) patients required reoperation within 90 days; 56% of patients (n = 27/48) experienced at least one grade 3 or higher AE (50% vs. 67%, p = 0.37). Ninety-day mortality was 2.0%. Readmission was less frequent in Arm 1 (16% vs. 42%, p = 0.05), but there were no differences between study arms in rates of reoperation (13% vs. 5%), pancreatic fistula or intra-abdominal abscess requiring drainage (9% vs. 16%), or wound infection (6% vs. 16%). Pancreatic fistula or intra-abdominal abscess requiring drainage was associated with receipt of adjuvant therapy (p = 0.012). No difference in overall survival was observed based on occurrence of postoperative AEs (hazard ratio = 1.1; 95% confidence interval 0.5-2.6).

Conclusions: In this multicenter study, rates of postoperative AEs were consistent with those previously reported. Multimodality trials of preoperative therapy for BR-PC may be performed in the cooperative group setting with careful quality assurance and safety monitoring.

Trial registration: Clinicaltrials.gov identifier: NCT02839343.

Keywords: Chemoradiation; Pancreatic cancer; Perioperative chemotherapy; Postoperative complications; Surgery.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Carcinoma, Pancreatic Ductal* / pathology
  • Carcinoma, Pancreatic Ductal* / surgery
  • Carcinoma, Pancreatic Ductal* / therapy
  • Combined Modality Therapy
  • Female
  • Fluorouracil* / administration & dosage
  • Follow-Up Studies
  • Humans
  • Irinotecan / administration & dosage
  • Leucovorin / administration & dosage
  • Male
  • Middle Aged
  • Neoadjuvant Therapy*
  • Oxaliplatin* / administration & dosage
  • Pancreatectomy*
  • Pancreatic Neoplasms* / pathology
  • Pancreatic Neoplasms* / surgery
  • Pancreatic Neoplasms* / therapy
  • Postoperative Complications* / etiology
  • Prognosis
  • Survival Rate

Substances

  • Oxaliplatin
  • Fluorouracil
  • Irinotecan
  • Leucovorin
  • folfirinox

Associated data

  • ClinicalTrials.gov/NCT02839343