Gemcitabine plus nab-paclitaxel until progression or alternating with FOLFIRI.3, as first-line treatment for patients with metastatic pancreatic adenocarcinoma: The Federation Francophone de Cancérologie Digestive-PRODIGE 37 randomised phase II study (FIRGEMAX).
Adenocarcinoma
/ drug therapy
Adult
Aged
Albumins
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Camptothecin
/ administration & dosage
Deoxycytidine
/ administration & dosage
Disease Progression
Drug Substitution
Female
Fluorouracil
/ administration & dosage
France
Humans
Irinotecan
/ administration & dosage
Leucovorin
/ administration & dosage
Male
Middle Aged
Neoadjuvant Therapy
Neoplasm Metastasis
Paclitaxel
/ administration & dosage
Pancreatic Neoplasms
/ drug therapy
Progression-Free Survival
Treatment Outcome
Gemcitabine
FOLFIRI.3
Gemcitabine
Nab-paclitaxel
Pancreatic cancer
Sequential treatment
Journal
European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
23
01
2020
revised:
21
04
2020
accepted:
09
05
2020
pubmed:
6
7
2020
medline:
7
1
2021
entrez:
6
7
2020
Statut:
ppublish
Résumé
Chemotherapy is effective in metastatic pancreatic adenocarcinoma (mPA), but new approaches are still needed to improve patients' survival and quality of life. We have previously published good efficacy and tolerability results on a sequential treatment strategy of gemcitabine followed by an intensified FOLFIRI (5FU+irinotecan) regimen. In the present study, we evaluated the same sequence but replaced gemcitabine by the new gemcitabine + nab-paclitaxel standard first-line combination. We randomised chemotherapy-naive patients with proven mPA, bilirubin levels ≤1.5 upper limit of normal values and performance status 0-2 to alternately receive gemcitabine + nab-paclitaxel for 2 months then FOLFIRI.3 for 2 months in arm A, or gemcitabine + nab-paclitaxel alone until progression in arm B. The primary objective was to increase the 6-month progression-free survival (PFS) rate from 40% (H Between November 2015 and November 2016, 127 patients were enrolled. Main grade III-IV toxicities (% in arm A/B) were: diarrhoea (12.5/1.7), neutropenia (46.9/31, including febrile neutropenia: 1.6/0), skin toxicity (6.3/13.8), and peripheral neuropathy (6.3/8.6). No toxic deaths occurred. The objective response rate was 40.3% (95% confidence interval [CI]: 28.1-53.6) in arm A and 26.7% (95% CI: 16.1-39.7) in arm B. The primary end-point (6-month PFS rate) was 45.2% [one-sided 95% CI: 34.3-56.4] in arm A and 23.3% in arm B [one-sided 95% CI: 14.3-32.3] in the mITT population. In the PP population, median PFS and OS were 7.6 months and 6 months and 14.5 months and 12.2 months in arm A and B, respectively. The FIRGEMAX strategy with gemcitabine + nab-paclitaxel alternating with FOLFIRI.3 every 2 months, appears feasible and effective, with manageable toxicities, in patients able to reach >2mo of treatment. EudraCT: 2014-004449-28: NCT: 0282701.
Sections du résumé
BACKGROUND
Chemotherapy is effective in metastatic pancreatic adenocarcinoma (mPA), but new approaches are still needed to improve patients' survival and quality of life. We have previously published good efficacy and tolerability results on a sequential treatment strategy of gemcitabine followed by an intensified FOLFIRI (5FU+irinotecan) regimen. In the present study, we evaluated the same sequence but replaced gemcitabine by the new gemcitabine + nab-paclitaxel standard first-line combination.
PATIENTS AND METHODS
We randomised chemotherapy-naive patients with proven mPA, bilirubin levels ≤1.5 upper limit of normal values and performance status 0-2 to alternately receive gemcitabine + nab-paclitaxel for 2 months then FOLFIRI.3 for 2 months in arm A, or gemcitabine + nab-paclitaxel alone until progression in arm B. The primary objective was to increase the 6-month progression-free survival (PFS) rate from 40% (H
RESULTS
Between November 2015 and November 2016, 127 patients were enrolled. Main grade III-IV toxicities (% in arm A/B) were: diarrhoea (12.5/1.7), neutropenia (46.9/31, including febrile neutropenia: 1.6/0), skin toxicity (6.3/13.8), and peripheral neuropathy (6.3/8.6). No toxic deaths occurred. The objective response rate was 40.3% (95% confidence interval [CI]: 28.1-53.6) in arm A and 26.7% (95% CI: 16.1-39.7) in arm B. The primary end-point (6-month PFS rate) was 45.2% [one-sided 95% CI: 34.3-56.4] in arm A and 23.3% in arm B [one-sided 95% CI: 14.3-32.3] in the mITT population. In the PP population, median PFS and OS were 7.6 months and 6 months and 14.5 months and 12.2 months in arm A and B, respectively.
CONCLUSIONS
The FIRGEMAX strategy with gemcitabine + nab-paclitaxel alternating with FOLFIRI.3 every 2 months, appears feasible and effective, with manageable toxicities, in patients able to reach >2mo of treatment.
TRIAL REGISTRATION INFORMATION
EudraCT: 2014-004449-28: NCT: 0282701.
Identifiants
pubmed: 32623182
pii: S0959-8049(20)30285-9
doi: 10.1016/j.ejca.2020.05.018
pii:
doi:
Substances chimiques
130-nm albumin-bound paclitaxel
0
Albumins
0
Deoxycytidine
0W860991D6
Irinotecan
7673326042
Paclitaxel
P88XT4IS4D
Leucovorin
Q573I9DVLP
Fluorouracil
U3P01618RT
Camptothecin
XT3Z54Z28A
Gemcitabine
0
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
25-34Investigateurs
Cécile Julien
(C)
Nicolas Barriere
(N)
Julie Gigout
(J)
Simon Pernot
(S)
Céline Lepere
(C)
Aziz Zaanan
(A)
Géraldine Perkins
(G)
Raymond Despax
(R)
Jérôme Chamois
(J)
Xavier Artignan
(X)
Pauline Regnault
(P)
Benoît Dupont
(B)
Maxime Lesouef
(M)
Leila Bengrine Lefevre
(L)
Julie Vincent
(J)
François Ghiringhelli
(F)
Mme E Barbier
(ME)
Morgan Andre
(M)
Johann Dreanic
(J)
Catherine Brezault-Bonnet
(C)
Valérie Boige
(V)
Antoine Holllebecque
(A)
Bruno Valenza
(B)
Gildas Phelip
(G)
Philippe Dominici
(P)
Marion Chauvenet
(M)
Frederick Moryoussef
(F)
Pierre-Luc Etienne
(PL)
Dominique Besson
(D)
Mathilde Martinez
(M)
Pamela Biondiani
(P)
Benoît Avisse
(B)
Marie-Pierre Galais
(MP)
Aurélie Parzy
(A)
Salvatore Caruso
(S)
Jean-François Codoul
(JF)
Iulia Pripon
(I)
Mustapha Atlassi
(M)
Oana Cojocarasu
(O)
Etienne Suc
(E)
Ahmed Bedjaoui
(A)
Philippe Houyau
(P)
Yann Berge
(Y)
Dany Gargot
(D)
Vincent Bourgeois
(V)
Pierre-Emmanuel Henneresse
(PE)
Sandrine Lavau Denes
(S)
Valérie Lebrun Lyat
(V)
Dominique Genet
(D)
Jean Martin
(J)
Pr Pierre Michel
(PP)
David Sefrioui
(D)
Anne Escande
(A)
Louis-Marie Dourthe
(LM)
Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest statement T.J. reported receiving honoraria from Merck, Roche, Amgen, Lilly, Sanofi, Samsung, MSD, Servier, Celgene, Pierre Fabre; has been a member of the consulting or advisory role for Roche, Merck KGaA, Amgen, Lilly, MSD, Servier, Pierre Fabre, Sanofi, Samsung; speakers' Bureau for Servier, Amgen, Roche, Sanofi, Merck, Lilly, Pierre Fabre. R.Y. reported receiving honoraria from Roche, Sanofi, Merck, Amgen, Bayer and Servier. B.J-.B reported receiving honoraria from Amgen, AstraZeneca, Bayer, Merck Serono, Pierre Fabre, Roche, Sanofi, Servier. All the remaining authors have declared no conflicts of interest.