Sequential therapy of refractory metastatic pancreatic cancer with 5-FU/LV/irinotecan (FOLFIRI) vs. 5-FU/LV/oxaliplatin (OFF). The PANTHEON trial (AIO PAK 0116)

J Cancer Res Clin Oncol. 2024 Jul 1;150(7):332. doi: 10.1007/s00432-024-05827-x.

Abstract

Purpose: In patients with metastatic pancreatic cancer, after failure of gemcitabine/nab-paclitaxel, this trial compares the efficacy of second-line therapy with FOLFIRI vs. OFF (1:1 randomisation) with cross-over to the vice-versa regimen as third-line therapy.

Patients and methods: The primary endpoint was PFS (progression-free survival: time from randomization until progression or death) of second-line therapy. The trial aimed to demonstrate non-inferiority of FOLFIRI vs OFF (non-inferiority margin of a hazard ratio (HR) of 1.5, power of 80% and a significance level of 5%, 196 events needed). Secondary endpoints included overall survival (OS), progression-free survival of third-line therapy and safety. The trial is registered with EudraCT Nr. 2016-004640-11.

Results: The trial was terminated with 60 evaluable (37 with FOLFIRI, 23 with OFF) patients due to insufficient recruitment. PFS of second-line therapy was 2.4 (95% CI 2.3-2.6) months with FOLFIRI vs 2.4 (95% CI 2.2-2.7) months with OFF (HR: 0.80, 95% CI 0.45-1.42, P = 0.43). OS was comparable between the arms (HR: 0.95, 95% CI 0.54-1.66), P = 0.84). Only 4 out of 28 (14%) patients receiving third-line therapy achieved a disease control (partial remission or stable disease). Both second-line regimens were well tolerated without new or unexpected safety signals being observed.

Conclusion: The exploratory analysis of this early terminated trial suggests that FOLFIRI and OFF have similar efficacy ant toxicity as second-line therapy of PDAC after failure of gemcitabine/nab-paclitaxel. Third-line therapy regardless of regimen does not provide satisfactory efficacy in this sequential treatment algorithm.

Keywords: Chemotherapy; FOLFIRI; Fluoropyrimidine; Metastatic; Oxaliplatin; Pancreatic cancer.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives
  • Camptothecin / therapeutic use
  • Cross-Over Studies
  • Female
  • Fluorouracil* / administration & dosage
  • Fluorouracil* / therapeutic use
  • Humans
  • Irinotecan* / administration & dosage
  • Irinotecan* / therapeutic use
  • Leucovorin* / administration & dosage
  • Leucovorin* / therapeutic use
  • Male
  • Middle Aged
  • Oxaliplatin* / administration & dosage
  • Oxaliplatin* / therapeutic use
  • Pancreatic Neoplasms* / drug therapy
  • Pancreatic Neoplasms* / pathology
  • Progression-Free Survival

Substances

  • Fluorouracil
  • Leucovorin
  • Oxaliplatin
  • Irinotecan
  • Camptothecin

Supplementary concepts

  • IFL protocol