Conversion to resection of liver metastases from colorectal cancer with hepatic artery infusion of combined chemotherapy and systemic cetuximab in multicenter trial OPTILIV
Mené sur 66 patients présentant des métastases hépatiques non résécables ayant pour origine un cancer colorectal sans mutation du gène KRAS (âge : 33 à 76 ans), cet essai multicentrique européen de phase II évalue, du point de vue du taux d'hépatectomie R0-R1, de la survie sans progression et de la survie globale, l'intérêt d'une perfusion artérielle hépatique d'irinotécan, d'oxaliplatine et de 5-fluorouracile en combinaison avec le cétuximab administré par voie intraveineuse
Background : Systemic chemotherapy typically converts previously unresectable liver metastases (LM) from colorectal cancer to curative intent resection in around 15% of patients. This European multicenter phase II trial tested whether hepatic artery infusion (HAI) with triplet chemotherapy and systemic cetuximab could increase this rate to 30% in previously treated patients. Patients and methods : Participants had unresectable LM from wt KRAS colorectal cancer. Main non-inclusion criteria were advanced extra hepatic disease, prior HAI and grade 3 neuropathy. Irinotecan (180 mg/m2), oxaliplatin (85 mg/m2) and 5-fluorouracil (2800 mg/m2) were delivered via an implanted HAI access port and combined with intravenous cetuximab (500 mg/m2) every 14 days. Multidisciplinary decisions to resect LM were taken after every 3 courses. The rate of macroscopic complete resections (R0+R1) of LM, progression-free-survival (PFS) and overall survival (OS) were computed according to intent to treat. Results : The patient population consisted of 42 men and 22 women, aged 33-76 years, with a median of 10 LM involving a median of six segments. Up to 3 extra-hepatic lesions of <1cm were found in 41% of the patients. A median of six courses was delivered. The primary endpoint was met, with R0-R1 hepatectomy for 19 of the 64 previously-treated patients - 29.7% [95% CI, 18.5-40.9]. Grade 3-4 neutropenia (42.6%), abdominal pain (26.2%), fatigue (18%), and diarrhea (16.4%) were frequent. Objective response rate was 40.6% [28.6-52.3]. Median PFS and OS reached 9.3 [7.8-10.9] and 25.5 months [18.8-32.1] respectively. Those with R0-R1 hepatectomy had a median OS of 35.2 months [32.6-37.8], with 37.4% [23.6-51.2] alive at 4-years. Conclusion : The coordination of liver-specific intensive chemotherapy and surgery had a high curative intent potential that deserves upfront randomized testing.