mFOLFIRINOX efficacy as rescue regimen for patients with metastatic refractory colorectal cancer: The RE-PLAY trial.

Abstract

3554 Background: Doublets with Fluoropyrimidines (F), oxaliplatin (Ox), and irinotecan (Ir) are standard chemotherapy agents used to treat metastatic colorectal cancer (mCCR). The role of triplet combination with modified FOLFIRINOX (mFOLFIRINOX) in refractory patients (pts) previously treated with doublets or monotherapy sequential regimens remains unclear. Methods: This single-arm, open-label phase II trial employed a Simon two-stage design. Eligible pts had mCCR with documented progression after treatment with doublets or sequential monotherapy regimens containing F, Ox, and Ir. Pts with RAS wild-type tumors were required to be refractory to anti-EGFR therapy. The mFOLFIRINOX regimen consisted of 5-FU (2400 mg/m², continuous infusion over 46 hours), Ox (85 mg/m², D1), Ir (150 mg/m², D1), and leucovorin (200 mg/m², D1), administered every 14 days. The primary endpoint was the disease control rate (DCR) as assessed by RECIST v1.1. According to the Simon design, the study would be considered positive if 4 or more pts achieve disease control among 25 pts in the second stage. Secondary endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Results: Between October 2021 and October 2024, 25 pts were enrolled. Three pts did not receive treatment due to consent withdrawal (n = 1) or clinical deterioration from disease progression before treatment initiation (n = 2). All pts had proficient mismatch repair (pMMR) tumors; 16 (64%) had KRAS/NRAS mutations, and most tumors were left-sided (n = 20, 80%). At Intention to Treat analyses, 16.6% (n = 4) achieved a partial response, 44% (n = 11) had stable disease, and 28% (n = 7) experienced disease progression as their best radiologic response. The DCR was 60% (n = 15), and the ORR was 16.6% (n = 4). With a median follow-up of 6.8 months, 17 pts experienced disease progression or death. The median PFS was 5.7 months, and the median OS was 9.3 months. No significant differences in DCR, ORR, PFS, or OS were observed based on RAS mutation status or tumor sidedness; among 22 pts who received at least one cycle of mFOLFIRINOX, 68.1% (n = 15) experienced grade 3 or higher adverse events, including one treatment-related death. Conclusions: mFOLFIRINOX demonstrated efficacy as a rescue regimen for refractory mCCR previously refractory to doublets or sequential monotherapy regimens containing Ox, Ir, fluoropyrimidines, and anti-EGFR therapy. Clinical trial information: NCT05354817 .