Hepatic arterial oxaliplatin plus intravenous 5-fluorouracil and cetuximab for first-line treatment of colorectal liver metastases: A multicenter phase II trial.
5-fluorouracil
Cetuximab
Hepatic arterial infusion chemotherapy
Liver metastases
Metastatic colorectal cancer
Oxaliplatin
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:
12 2023
12 2023
Historique:
received:
14
08
2023
revised:
17
10
2023
accepted:
19
10
2023
medline:
27
11
2023
pubmed:
6
11
2023
entrez:
3
11
2023
Statut:
ppublish
Résumé
The efficacy and tolerability of hepatic arterial infusion (HAI) oxaliplatin plus systemic 5-fluorouracil and cetuximab as frontline treatment in patients with colorectal liver metastases (CRLM) are unknown. In this multicenter, single-arm phase II study, patients with CRLM not amenable to curative-intent resection or requiring complex/major liver resection, and no prior chemotherapy for metastatic disease, received HAI oxaliplatin and intravenous 5-fluorouracil, leucovorin and cetuximab, every two weeks until disease progression, limiting toxicity or at least 3 months after complete response or curative-intent resection/ablation. The primary endpoint was overall response rate (ORR). 35 patients, mostly with bilateral (89%), multiple CRLM (>4, 86%; >10, 46%) were enrolled in eight centers. The ORR was 88% (95% CI, 71%-96%) among evaluable patients (n = 32), and 95% (95% CI 70-100%) among the 22 wild-type RAS/BRAF evaluable patients. After a median follow-up of 8.8 years (95% CI, 8.7-not reached), median progression-free survival was 17.9 months (95% CI, 15-23) and median overall survival (OS) was 46.3 months (95% CI, 40.0-not reached). 23 of the 35 patients (66%), including 22 (79%) of the 25 patients with wild-type RAS tumor, underwent curative-intent surgical resection and/or ablation of CRLM. HAI catheter remained patent in 86% of patients, allowing for a median of eight oxaliplatin infusions (range, 1-19). Treatment toxicity was manageable, without toxic death. HAI oxaliplatin plus systemic 5-fluorouracil and cetuximab appears highly effective in the frontline treatment of patients with unresectable CRLM and should be investigated further.
Sections du résumé
BACKGROUND
The efficacy and tolerability of hepatic arterial infusion (HAI) oxaliplatin plus systemic 5-fluorouracil and cetuximab as frontline treatment in patients with colorectal liver metastases (CRLM) are unknown.
METHODS
In this multicenter, single-arm phase II study, patients with CRLM not amenable to curative-intent resection or requiring complex/major liver resection, and no prior chemotherapy for metastatic disease, received HAI oxaliplatin and intravenous 5-fluorouracil, leucovorin and cetuximab, every two weeks until disease progression, limiting toxicity or at least 3 months after complete response or curative-intent resection/ablation. The primary endpoint was overall response rate (ORR).
RESULTS
35 patients, mostly with bilateral (89%), multiple CRLM (>4, 86%; >10, 46%) were enrolled in eight centers. The ORR was 88% (95% CI, 71%-96%) among evaluable patients (n = 32), and 95% (95% CI 70-100%) among the 22 wild-type RAS/BRAF evaluable patients. After a median follow-up of 8.8 years (95% CI, 8.7-not reached), median progression-free survival was 17.9 months (95% CI, 15-23) and median overall survival (OS) was 46.3 months (95% CI, 40.0-not reached). 23 of the 35 patients (66%), including 22 (79%) of the 25 patients with wild-type RAS tumor, underwent curative-intent surgical resection and/or ablation of CRLM. HAI catheter remained patent in 86% of patients, allowing for a median of eight oxaliplatin infusions (range, 1-19). Treatment toxicity was manageable, without toxic death.
CONCLUSION
HAI oxaliplatin plus systemic 5-fluorouracil and cetuximab appears highly effective in the frontline treatment of patients with unresectable CRLM and should be investigated further.
Identifiants
pubmed: 37922632
pii: S0959-8049(23)00702-5
doi: 10.1016/j.ejca.2023.113400
pii:
doi:
Substances chimiques
Oxaliplatin
04ZR38536J
Cetuximab
PQX0D8J21J
Fluorouracil
U3P01618RT
Leucovorin
Q573I9DVLP
Types de publication
Multicenter Study
Clinical Trial, Phase II
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
113400Informations de copyright
Copyright © 2023 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: DM: Consulting/advisory role: AbbVie, Amgen, AstraZeneca, Bayer, Bionest Partners, BMS, Incyte, Merck Serono, MSD, Pierre Fabre, Roche, Sanofi, Simon-Kutcher & Partners, Servier, Taiho. Honoraria for lectures: Amgen, AstraZeneca, Bayer, BMS, Foundation Medicine, Incyte, Leo Pharma, Merck Serono, MSD, Pierre Fabre, Roche, Sanofi, Servier, Veracyte, Viatris. Personal fees for a writing engagement: Medscape. Travel expenses for medical congresses: Amgen, Bayer, BMS, Merck Serono, MSD, Pierre Fabre, Roche, Sanofi, Servier, Viatris. BV: none. MF: honoraria for lectures: Novartis. Travel expenses for medical congresses: Ipsen. RG: Consulting/advisory role: Pierre Fabre, BMS, Servier, MSD. Honoraria for lectures: MSD, Servier, Ipsen, BMS, Viatris. Travel expenses for medical congresses: MSD, Ipsen, Roche, Pierre Fabre, Advanced Accelerator Applications (AAA). CC: none. JE: Consulting/advisory role: MSD, Eisai, BMS, AstraZeneca, Bayer, Roche, Ipsen, Basilea, Merck Serono, Incyte, Servier, Beigene. Travel expenses for medical congresses: Amgen. Research funding (institutional): BMS, Beigene. MPG: honoraria: Servier, BMS. Travel expenses for medical congresses: AAA, Bayer, Servier, Amgen. LBG: honoraria: AstraZeneca, Servier, KSK, MSD, Bayer, Eisai. DS: travel expenses for medical congresses: Servier, Pierre Fabre. EDB: none. TDB: Consulting/advisory role: Terumo, Boston Scientific. Research funding (institutional): Quantum, Terumo. DG: honoraria for lectures: Merck Serono, Amgen, Sanofi, Servier. PD: Consulting/advisory role: MSD. Honoraria for lectures: AstraZeneca, MSD. Travel expenses for medical congresses: MSD. LL: none. VB: Consulting/advisory role: Merck Serono, Ipsen, Bayer, Eisai, BMS, Roche, AstraZeneca. Honoraria for lectures: Merck Serono, Novartis, Roche, Bayer, MSD, Amgen, Ipsen, AstraZeneca. Travel expenses for medical congresses: Amgen, Merck Serono, Sanofi Genzyme, Bayer, Roche, MSD, Ipsen, AstraZeneca. Research funding (institutional): Merck Serono. MG: none. JPP: none. MD: honoraria for advisory boards or as a presenter in symposium: Merck Serono, MSD, Amgen, Roche, Bayer, Ipsen, Pfizer, Servier, Pierre Fabre, Lilly, Sanofi, Servier, Daiichi Sankyo.