First-line FOLFOXIRI-based Chemotherapy for Unresectable Metastatic Colorectal Cancer: Real-world Outcomes, Safety,...

In Japan, contemporary real-world data that simultaneously assess effectiveness, safety, conversion feasibility, and long-term outcomes of first-line FOLFOXIRI-based chemotherapy for unresectable metastatic colorectal cancer (mCRC) remain limited. Here, we aimed to evaluate the real-world efficacy, safety, and long-term outcomes of this treatment as well as to identify factors associated with conversion surgery.

We conducted a retrospective single-center cohort study of consecutive patients with first-line FOLFOXIRI (±targeted agent). Progression-free survival (PFS) encompassed the entire first-line treatment period. Survival outcomes were analyzed using Kaplan-Meier and log-rank tests, with hazard ratios (HRs) estimated by Cox models. Adverse events (AEs) were graded according to CTCAE v5.0.

Of 59 patients (median FOLFOXIRI cycles: 7), bevacizumab was administered to 74.6%. The objective response rate was 66.1% and the disease control rate was 88.1%. Conversion surgery was achieved in 27.1% of patients, with R0 resection in 23.7% of the cohort. Patients undergoing conversion surgery had longer PFS and overall survival (OS) than those who did not. Conversion was associated with rectal primaries and the absence of peritoneal metastasis. In RAS-stratified analyses, PFS was similar, whereas OS was shorter in RAS-mutant tumors. Grade ≥3 neutropenia and febrile neutropenia occurred in 72.9% and 25.4% of patients, respectively; severe non-hematological AEs were rare, and no treatment-related deaths occurred.

In Japanese practice, first-line FOLFOXIRI achieved substantial disease control and clinically meaningful survival with manageable toxicity. R0 conversion was achieved in the subset with longer survival. A conversion-oriented triplet induction strategy may be considered for rectal cancer without peritoneal metastasis, irrespective of RAS status.