554MO - Cetuximab plus FOLFOXIRI versus cetuximab plus FOLFOX in <italic>RAS</italic> wild-type patients with initially unresectable colorectal liver metastases: The TRICE randomized clinical trial

Background

The TRICE study was designed to determine whether intensifying the chemotherapy backbone in cetuximab-containing regimens could confer additional clinical benefits to RAS wild-type colorectal cancer (CRC) patients with initially unresectable liver metastases.

Methods

Patients were randomly assigned to receive either cetuximab plus FOLFOXIRI (triplet arm) or cetuximab plus FOLFOX (doublet arm) every 2 weeks. Primary efficacy analyses were conducted based on the intention-to-treat population, while safety analyses were performed on patients who received at least one line of chemotherapy. The primary end point was the objective response rate (ORR). Secondary end points included the median depth of tumor response (DpR), early tumor shrinkage (ETS), R0 resection rate, progression-free survival (PFS), overall survival (OS), and treatment-related adverse events.

Results

From January 2018 to December 2022, 146 patients were randomized to the cetuximab plus FOLFOXIRI (n = 72) or the cetuximab plus FOLFOX (n = 74) treatment arms. The ORR was comparable with 84.7% versus 79.7% in the triplet and doublet arms, respectively (OR = 0.71, 95% CI 0.30 to 1.67; P = .43). Although intensifying the chemotherapy backbone led to a higher median DpR (59.6% vs. 55.0%; P = .039), other secondary outcomes remained comparable between the two arms. At a median follow-up of 26.2 months, the median PFS was 11.7 months in the triplet arm vs. 13.4 months in the doublet arm (HR = 1.37, 95% CI 0.91 to 2.07; P = .13). Additionally, the triplet arm was associated with a higher incidence of grade 3-4 neutropenia (44.1% vs. 27.0%; P = .03) and diarrhea (5.9% vs. 0%; P = .03).

Conclusions

Although intensifying upfront systemic chemotherapy in RAS wild-type metastatic CRC patients offered a better depth of tumor response, there was an increase in neutropenia and diarrhea incidence with no significant difference in ORR, PFS, and R0 resection rate.

Clinical trial identification

NCT03493048.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.