Impact of age and gender on the efficacy and safety of upfront therapy with panitumumab plus FOLFOX followed by panitumumab-based maintenance: a pre-specified subgroup analysis of the Valentino study.
age
anti-EGFR
colorectal cancer
gender
metastasis
Journal
ESMO open
ISSN: 2059-7029
Titre abrégé: ESMO Open
Pays: England
ID NLM: 101690685
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
23
06
2021
revised:
23
07
2021
accepted:
28
07
2021
pubmed:
21
8
2021
medline:
30
10
2021
entrez:
20
8
2021
Statut:
ppublish
Résumé
The safety and efficacy outcome of elderly metastatic colorectal cancer (mCRC) patients fit enough to receive combination chemotherapy plus biological agents is an issue of growing interest. Also, gender-specific differential toxicity and efficacy of anti-epidermal growth factor receptor (EGFR)-based upfront treatments need to be explored. Valentino was a multicenter, randomized, phase II trial, investigating two panitumumab-based maintenance strategies following first-line panitumumab plus FOLFOX in RAS wild-type mCRC patients. We carried out a subgroup analysis, aimed at assessing the differences in efficacy, safety and quality of life (QoL) according to age (<70 versus ≥70 years) and gender (male versus female). Efficacy endpoints were progression-free survival (PFS), overall survival (OS) and overall response rate (ORR); safety endpoints were rates of any grade and grade 3/4 adverse events (AEs). No significant differences in terms of PFS, OS and ORR were observed between patients aged <70 or ≥70 years and the effect of the maintenance treatment arm on survival outcomes was similar in the two subgroups. The safety profile of both induction and maintenance treatment and the impact on QoL were similar in elderly and younger patients. No significant differences in PFS, OS, ORR or clinical benefit rate were observed according to gender. A significantly higher rate of overall grade 3/4 AEs (P = 0.008) and of grade 3/4 thrombocytopenia (P = 0.017), any grade and grade 3/4 neutropenia (P < 0.0001) and any grade conjunctivitis (P = 0.033) was reported in female as compared to male patients. Conversely, we reported a significantly higher incidence of any grade skin rash (P = 0.0007) and hypomagnesemia (P = 0.029) in male patients. The upfront choice of an anti-EGFR-based doublet chemotherapy followed by a maintenance strategy represents a valuable option in RAS wild-type mCRC irrespective of gender and age, though a careful evaluation of patients to maximize the risk/benefit ratio is warranted.
Sections du résumé
BACKGROUND
The safety and efficacy outcome of elderly metastatic colorectal cancer (mCRC) patients fit enough to receive combination chemotherapy plus biological agents is an issue of growing interest. Also, gender-specific differential toxicity and efficacy of anti-epidermal growth factor receptor (EGFR)-based upfront treatments need to be explored.
PATIENTS AND METHODS
Valentino was a multicenter, randomized, phase II trial, investigating two panitumumab-based maintenance strategies following first-line panitumumab plus FOLFOX in RAS wild-type mCRC patients. We carried out a subgroup analysis, aimed at assessing the differences in efficacy, safety and quality of life (QoL) according to age (<70 versus ≥70 years) and gender (male versus female). Efficacy endpoints were progression-free survival (PFS), overall survival (OS) and overall response rate (ORR); safety endpoints were rates of any grade and grade 3/4 adverse events (AEs).
RESULTS
No significant differences in terms of PFS, OS and ORR were observed between patients aged <70 or ≥70 years and the effect of the maintenance treatment arm on survival outcomes was similar in the two subgroups. The safety profile of both induction and maintenance treatment and the impact on QoL were similar in elderly and younger patients. No significant differences in PFS, OS, ORR or clinical benefit rate were observed according to gender. A significantly higher rate of overall grade 3/4 AEs (P = 0.008) and of grade 3/4 thrombocytopenia (P = 0.017), any grade and grade 3/4 neutropenia (P < 0.0001) and any grade conjunctivitis (P = 0.033) was reported in female as compared to male patients. Conversely, we reported a significantly higher incidence of any grade skin rash (P = 0.0007) and hypomagnesemia (P = 0.029) in male patients.
CONCLUSIONS
The upfront choice of an anti-EGFR-based doublet chemotherapy followed by a maintenance strategy represents a valuable option in RAS wild-type mCRC irrespective of gender and age, though a careful evaluation of patients to maximize the risk/benefit ratio is warranted.
Identifiants
pubmed: 34416469
pii: S2059-7029(21)00207-6
doi: 10.1016/j.esmoop.2021.100246
pmc: PMC8379288
pii:
doi:
Substances chimiques
Panitumumab
6A901E312A
Fluorouracil
U3P01618RT
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
100246Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Disclosure FP has received honoraria for speaker activities and participation in advisory boards from Sanofi, Amgen, Bayer, Merck-Serono, Lilly, Roche and Servier and research grants from BMS. SL has received honoraria for speaker activities and participation in advisory boards from Amgen, Bayer, Merck-Serono, Roche, Servier and Bristol-Myers Squibb. AZ has received honoraria for speaker bureau from Amgen, Merck, Servier and Bayer. SC has received honoraria for participation in advisory boards from Merck. MDB has received honoraria for speaker activities and participation in advisory boards from Amgen, Roche, Lilly, Servier, Incyte and Celgene. FM has received honoraria for speaker activities from Servier. The remaining authors have declared no conflicts of interest.