Impact of age and gender on the safety and efficacy of chemotherapy plus bevacizumab in metastatic colorectal cancer: a pooled analysis of TRIBE and TRIBE2 studies.
Age Factors
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Bevacizumab
/ administration & dosage
Camptothecin
/ administration & dosage
Colorectal Neoplasms
/ drug therapy
Female
Fluorouracil
/ administration & dosage
Humans
Kaplan-Meier Estimate
Leucovorin
/ administration & dosage
Male
Middle Aged
Nausea
/ chemically induced
Neoplasm Metastasis
Organoplatinum Compounds
/ administration & dosage
Progression-Free Survival
Sex Characteristics
Treatment Outcome
Vomiting
/ chemically induced
FOLFOXIRI/bevacizumab
age
gender
metastatic colorectal cancer
Journal
Annals of oncology : official journal of the European Society for Medical Oncology
ISSN: 1569-8041
Titre abrégé: Ann Oncol
Pays: England
ID NLM: 9007735
Informations de publication
Date de publication:
01 12 2019
01 12 2019
Historique:
pubmed:
2
10
2019
medline:
28
7
2020
entrez:
2
10
2019
Statut:
ppublish
Résumé
The phase III TRIBE and TRIBE2 studies randomized metastatic colorectal cancer patients to first-line FOLFOXIRI/bevacizumab or a doublet (FOLFIRI or FOLFOX)/bevacizumab. The studies demonstrated a significant benefit from the triplet at the price of an increased incidence of chemotherapy-related adverse events (AEs). In both trials, males and females aged between 18 and 70 years with ECOG PS ≤2 and between 71 and 75 years with ECOG PS = 0 were eligible. We investigated the effect of FOLFOXIRI/bevacizumab versus doublets/bevacizumab according to age and gender. Subgroup analyses according to age (<70 versus 70-75 years) and gender were carried out for overall response rate (ORR), progression-free survival (PFS), and AE rates. Of 1187 patients, 1005 (85%) were aged <70 years and 182 (15%) 70-75 years; 693 (58%) were males and 494 (42%) females. There was no evidence of interaction between age or gender and the benefit provided by the intensification of the upfront chemotherapy in terms of ORR and PFS, or the increased risk of experiencing G3/4 AEs. Elderly patients and females experienced higher rates of overall G3/4 AEs (73% versus 60%, P < 0.01 and 69% versus 57%, P < 0.01, respectively). Notably, in the FOLFOXIRI/bevacizumab subgroup, G3/4 diarrhea and febrile neutropenia occurred in 27% and 16% of elderly patients, respectively, while females reported high incidences of any grade nausea (67%) and vomiting (50%). The improvements in terms of ORR and PFS of FOLFOXIRI/bevacizumab versus doublets/bevacizumab are independent of gender and age, with a similar relative increase in AEs among elderly patients and females. Initial dose reductions and possibly primary G-CSF prophylaxis should be recommended for patients between 70 and 75 years old treated with FOLFOXIRI/bevacizumab, and a careful management of antiemetic prophylaxis should be considered among females.
Sections du résumé
BACKGROUND
The phase III TRIBE and TRIBE2 studies randomized metastatic colorectal cancer patients to first-line FOLFOXIRI/bevacizumab or a doublet (FOLFIRI or FOLFOX)/bevacizumab. The studies demonstrated a significant benefit from the triplet at the price of an increased incidence of chemotherapy-related adverse events (AEs). In both trials, males and females aged between 18 and 70 years with ECOG PS ≤2 and between 71 and 75 years with ECOG PS = 0 were eligible. We investigated the effect of FOLFOXIRI/bevacizumab versus doublets/bevacizumab according to age and gender.
PATIENTS AND METHODS
Subgroup analyses according to age (<70 versus 70-75 years) and gender were carried out for overall response rate (ORR), progression-free survival (PFS), and AE rates.
RESULTS
Of 1187 patients, 1005 (85%) were aged <70 years and 182 (15%) 70-75 years; 693 (58%) were males and 494 (42%) females. There was no evidence of interaction between age or gender and the benefit provided by the intensification of the upfront chemotherapy in terms of ORR and PFS, or the increased risk of experiencing G3/4 AEs. Elderly patients and females experienced higher rates of overall G3/4 AEs (73% versus 60%, P < 0.01 and 69% versus 57%, P < 0.01, respectively). Notably, in the FOLFOXIRI/bevacizumab subgroup, G3/4 diarrhea and febrile neutropenia occurred in 27% and 16% of elderly patients, respectively, while females reported high incidences of any grade nausea (67%) and vomiting (50%).
CONCLUSIONS
The improvements in terms of ORR and PFS of FOLFOXIRI/bevacizumab versus doublets/bevacizumab are independent of gender and age, with a similar relative increase in AEs among elderly patients and females. Initial dose reductions and possibly primary G-CSF prophylaxis should be recommended for patients between 70 and 75 years old treated with FOLFOXIRI/bevacizumab, and a careful management of antiemetic prophylaxis should be considered among females.
Identifiants
pubmed: 31573612
pii: S0923-7534(20)32558-8
doi: 10.1093/annonc/mdz403
pii:
doi:
Substances chimiques
Organoplatinum Compounds
0
Bevacizumab
2S9ZZM9Q9V
Leucovorin
Q573I9DVLP
Fluorouracil
U3P01618RT
Camptothecin
XT3Z54Z28A
Types de publication
Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1969-1977Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.