Hepatic arterial oxaliplatin plus intravenous 5-fluorouracil and cetuximab for first-line treatment of colorectal liver metastases: A multicenter phase II trial.

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.
Competing Interests: 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.
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