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Randomized Controlled Trial
. 2024 Jul 1;150(7):332.
doi: 10.1007/s00432-024-05827-x.

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)

Dominik Paul Modest  1   2 , Volker Heinemann  3   4 , Philipp Schütt  5 , Stefan Angermeier  6 , Mike Haberkorn  7 , Oliver Waidmann  8 , Ullrich Graeven  9 , Kai Wille  10 , Volker Kunzmann  11 , Larissa Henze  12 , Christian Constantin  13 , Maike de Wit  14 , Claudio Denzlinger  15 , Alexej Ballhausen  16 , Annika Kurreck  16 , Ivan Jelas  16 , Annabel Helga Sophie Alig  16 , Arndt Stahler  16 , Sebastian Stintzing  16   3 , Helmut Oettle  17
Affiliations
Randomized Controlled Trial

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)

Dominik Paul Modest et al. J Cancer Res Clin Oncol. .

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.

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Conflict of interest statement

UG: honoraria/Advisory role: Boehringer INgelheim, AstraZeneca, Bristol-Myers-Squibb, MSD, Sanofi, Fujifilm, Novartis, Amgen. Travel support: GSK, Boehringer-Ingelheim, Amgen, Merck KGaA AHSA: Honoraria: MSD, Merck CD: Honoraria: Abbvie, Bayer, Celgene, Incyte, Janssen, Novartis HO: research funding: Bristol, Servier SS: honoraria: Amgen, AstraZeneca, Bayer, BMS, ESAI, Leo Pharma, Lilly, Merck, MSD, PierreFabre, Roche, Sanofi, Servier, Taiho, Takeda. Research funding: Merck, Pierre Fabre, Servier, Roche, MSD, Novartis, Biontech, ISofol, Mirati, Amgen AK: Honoraria: Merck AS: Honoraria: Roche, Servier, Taiho, Amgen, Pfizer, Lilly, Merck OW: honoraria: Amgen, Bayer, BMS, Celgene, Eisai, Incyte, Ipsen, MerckSerono, MSD, Novartis, Roche, Servier, AstraZeneca. Travel support: Abbvie, Bayer, BMS, Gilead, Ipsen, Medac, Merck. research funding (inst): Merck VH: Honoraria: Merck, Amgen, Roche, Sanofi, Sirtex, Servier, Pfizer, Pierre-Fabre, AstraZeneca, BMS; MSD, Novartis, Boehringer-INgelheim, Celgene, Terumo, Oncosil, Seagen. Support to institution: Merck, Amgen, Roche, Sanofi, Pfizer, Boeringer-Ingelheim, Sirtex, Servier DPM: Honoraria: Merck, Amgen, Servier, AstraZenenca, MSD, Sanofi, Lilly, Pierre-Fabre, Seagen, Onkowissen, IKF, MCI-Deutschland, Jörg Eickeler Veranstaltungen, Taiho, Takeda, Medscape, Cor2ED, G1, 21up, FOMF, Aptitude, GSK. Travel support: Merck, Amgen, Servier. Research funding (inst): Servier, Amgen

Figures

Fig. 1
Fig. 1
Study design. FOLFIRI denotes irinotecan, 5-fluorouracil and folinic acid. OFF denotes 5-fluorouracil, folinic acid and oxaliplatin
Fig. 2
Fig. 2
Consort diagram. FOLFIRI denotes irinotecan, 5-fluorouracil and folinic acid. OFF denotes 5-fluorouracil, folinic acid and oxaliplatin
Fig. 3
Fig. 3
Kaplan–Meier estimates of the full analysis set for PFS, PFS3, TTFS and OS. Indicated hazard ratios derived from Cox regression testing. P-values derived from log rank tests. A Kaplan–Meier estimate of progression-free survival of second-line therapy (primary endpoint), B Kaplan–Meier estimate of progression-free survival of third-line therapy (secondary endpoint), C Kaplan–Meier estimate of time to failure of strategy (secondary endpoint), D Kaplan–Meier estimate of overall survival (secondary endpoint),
See this image and copyright information in PMC

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