Three fluoropyrimidine-based regimens in routine clinical practice after nab-paclitaxel plus gemcitabine for metastatic pancreatic cancer: An AGEO multicenter study.
Adenocarcinoma
/ drug therapy
Adult
Aged
Aged, 80 and over
Albumins
/ adverse effects
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Camptothecin
/ adverse effects
Deoxycytidine
/ adverse effects
Female
Fluorouracil
/ adverse effects
Humans
Irinotecan
/ adverse effects
Leucovorin
/ adverse effects
Male
Middle Aged
Organoplatinum Compounds
/ adverse effects
Oxaliplatin
/ adverse effects
Paclitaxel
/ adverse effects
Pancreatic Neoplasms
/ drug therapy
Prospective Studies
Treatment Failure
Gemcitabine
FOLFIRI
FOLFIRINOX
FOLFOX
Metastatic pancreatic cancer
Nab-paclitaxel plus gemcitabine
Second-line chemotherapy
Journal
Clinics and research in hepatology and gastroenterology
ISSN: 2210-741X
Titre abrégé: Clin Res Hepatol Gastroenterol
Pays: France
ID NLM: 101553659
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
04
02
2019
revised:
07
08
2019
accepted:
26
08
2019
pubmed:
15
10
2019
medline:
9
9
2021
entrez:
15
10
2019
Statut:
ppublish
Résumé
A combination of nab-paclitaxel plus gemcitabine (N+G) has recently become a standard first-line treatment in patients with metastatic pancreatic adenocarcinoma (MPA), but there are currently no published data concerning second-line treatment after N+G. The aim of this study was to evaluate the survival outcomes and tolerability of three usual fluoropyrimidine-based regimens FOLFOX, FOLFIRI and FOLFIRINOX after N+G failure in MPA patients. Patients receiving N+G as first-line regimen were prospectively identified in 11 French centers between January 2014 and January 2017. After disease progression or unacceptable toxicity, patients eligible for second-line therapy were enrolled in the study. The primary endpoint was overall survival following the second-line regimen. Secondary endpoints were objective response, progression-free survival and safety. Out of 137 patients treated with N+G as first-line regimen, 61 (44.5%) received second-line chemotherapy, including FOLFOX (39.4%), FOLFIRI (34.4%) or FOLFIRINOX (26.2%). Baseline characteristics were not different between the 3 groups. In particular, median age was 71.7 years, sex ratio was 1/1, and performance status (PS) was 0 in 11.5% of case. Main grade 3 toxicities were neutropenia (4.9%) and nausea (3.3%), without major differences between the groups. No toxic death was observed. Median second-line progression-free survival (PFS) and overall survival (OS) were 2.95 (95% CI: 2.3-5.4) and 5.97 months (95% CI: 4.0-8.0), respectively, with no difference between the 3 groups. Median OS from the start of first-line chemotherapy was 12.7 months (10.4-15.1) and was significantly better in patients receiving FOLFIRI after N+G failure, 18.4 months (95% CI: 11.7-24.1, P<0.05), as compared with FOLFOX or FOLFIRINOX (10.4 and 12.3 months, respectively). This study suggests that second-line fluoropyrimidine-based regimens after N+G failure are feasible, have a manageable toxicity profile in selected patients with MPA, and are associated with promising clinical outcomes, in particular when combined with irinotecan. Randomized phase 3 trials are needed to confirm this trend.
Sections du résumé
BACKGROUND
A combination of nab-paclitaxel plus gemcitabine (N+G) has recently become a standard first-line treatment in patients with metastatic pancreatic adenocarcinoma (MPA), but there are currently no published data concerning second-line treatment after N+G. The aim of this study was to evaluate the survival outcomes and tolerability of three usual fluoropyrimidine-based regimens FOLFOX, FOLFIRI and FOLFIRINOX after N+G failure in MPA patients.
METHODS
Patients receiving N+G as first-line regimen were prospectively identified in 11 French centers between January 2014 and January 2017. After disease progression or unacceptable toxicity, patients eligible for second-line therapy were enrolled in the study. The primary endpoint was overall survival following the second-line regimen. Secondary endpoints were objective response, progression-free survival and safety.
RESULTS
Out of 137 patients treated with N+G as first-line regimen, 61 (44.5%) received second-line chemotherapy, including FOLFOX (39.4%), FOLFIRI (34.4%) or FOLFIRINOX (26.2%). Baseline characteristics were not different between the 3 groups. In particular, median age was 71.7 years, sex ratio was 1/1, and performance status (PS) was 0 in 11.5% of case. Main grade 3 toxicities were neutropenia (4.9%) and nausea (3.3%), without major differences between the groups. No toxic death was observed. Median second-line progression-free survival (PFS) and overall survival (OS) were 2.95 (95% CI: 2.3-5.4) and 5.97 months (95% CI: 4.0-8.0), respectively, with no difference between the 3 groups. Median OS from the start of first-line chemotherapy was 12.7 months (10.4-15.1) and was significantly better in patients receiving FOLFIRI after N+G failure, 18.4 months (95% CI: 11.7-24.1, P<0.05), as compared with FOLFOX or FOLFIRINOX (10.4 and 12.3 months, respectively).
CONCLUSION
This study suggests that second-line fluoropyrimidine-based regimens after N+G failure are feasible, have a manageable toxicity profile in selected patients with MPA, and are associated with promising clinical outcomes, in particular when combined with irinotecan. Randomized phase 3 trials are needed to confirm this trend.
Identifiants
pubmed: 31607641
pii: S2210-7401(19)30193-7
doi: 10.1016/j.clinre.2019.08.009
pii:
doi:
Substances chimiques
130-nm albumin-bound paclitaxel
0
Albumins
0
Organoplatinum Compounds
0
folfirinox
0
Oxaliplatin
04ZR38536J
Deoxycytidine
0W860991D6
Irinotecan
7673326042
Paclitaxel
P88XT4IS4D
Leucovorin
Q573I9DVLP
Fluorouracil
U3P01618RT
Camptothecin
XT3Z54Z28A
Gemcitabine
0
Types de publication
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
295-301Informations de copyright
Copyright © 2019. Published by Elsevier Masson SAS.