Treatment Intensification with Hepatic Arterial Infusion Chemotherapy in Patients with Liver-Only Colorectal Metastases Still Unresectable After Systemic Induction Chemotherapy: Exploratory Findings From a Prematurely Closed Multicenter Randomized Phase II Study: SULTAN UCGI 30/PRODIGE 53 (NCT03164655).

BACKGROUND

Hepatic arterial infusion (HAI) oxaliplatin represents a promising treatment option in patients with unresectable liver-only colorectal metastases (CRLM).

METHODS

In this randomized phase II study, we evaluated the efficacy of an intensification strategy based on HAI oxaliplatin combined with systemic chemotherapy (sys-CT) as a salvage treatment in patients with CRLM still unresectable after first-line induction sys-CT. The primary objective was conversion to resection/ablation (CTR). A real-life retrospective cohort of consecutive patients treated with HAI oxaliplatin + sys-CT in the same setting was also analyzed.

RESULTS

The study was stopped prematurely because of slow enrollment. Among 26 patients (13 men [50%]; median age 60 years) enrolled in 2018-2021, 11 were randomized in arm A (HAI + sys-CT, percutaneously placed catheters) and nine in arm B (sys-CT). CRLM were synchronous in 89% of patients, and 55% had RAS mutations. The CTR was 64% (7/11) in arm A and 22% (2/9) in arm B (odds ratio 0.16; 95% confidence interval 0.02-1.2; p = 0.09). Objective tumor response was 80% (8/10) in arm A and 11% (1/9) in arm B. Median overall survival was not reached in arm A versus 16.6 months in arm B (p = 0.008). Progression-free survival was significantly longer in arm A (12.6 vs. 4.37 months, p = 0.002). In the retrospective cohort of 35 patients, objective tumor response and CTR were 64% and 34%, respectively. Overall, HAI-related toxicity was manageable.

CONCLUSIONS

Because the number of enrolled patients was lower than expected, our study could not confirm that salvage HAI combined with sys-CT improved CTR and survival outcomes compared with Sys-CT alone. However, these encouraging exploratory results warrant further prospective studies.

TRIAL REGISTRATION: ClinicalTrials.gov, (NCT03164655). Trial registration date: 11th May 2017. https://clinicaltrials.gov/ct2/show/NCT03164655.