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).
Humans
Pancreatic Neoplasms
/ drug therapy
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Male
Fluorouracil
/ administration & dosage
Female
Middle Aged
Leucovorin
/ administration & dosage
Aged
Oxaliplatin
/ administration & dosage
Irinotecan
/ administration & dosage
Adult
Camptothecin
/ analogs & derivatives
Progression-Free Survival
Cross-Over Studies
Chemotherapy
FOLFIRI
Fluoropyrimidine
Metastatic
Oxaliplatin
Pancreatic cancer
Journal
Journal of cancer research and clinical oncology
ISSN: 1432-1335
Titre abrégé: J Cancer Res Clin Oncol
Pays: Germany
ID NLM: 7902060
Informations de publication
Date de publication:
01 Jul 2024
01 Jul 2024
Historique:
received:
02
04
2024
accepted:
31
05
2024
medline:
2
7
2024
pubmed:
2
7
2024
entrez:
1
7
2024
Statut:
epublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 38951245
doi: 10.1007/s00432-024-05827-x
pii: 10.1007/s00432-024-05827-x
doi:
Substances chimiques
Fluorouracil
U3P01618RT
Leucovorin
Q573I9DVLP
Oxaliplatin
04ZR38536J
Irinotecan
7673326042
Camptothecin
XT3Z54Z28A
Types de publication
Journal Article
Randomized Controlled Trial
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
332Informations de copyright
© 2024. The Author(s).
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