Preliminary results of fruquintinib in combination with FOLFIRI as second-line treatment for RAS-mutant metastatic colorectal cancer: A prospective, single-center phase 2 study.

Abstract

e15541 Background: Bevacizumab plus FOLFIRI therapy is currently the standard second-line treatment for RAS-mutant metastatic colorectal cancer (mCRC); however, its efficacy is limited. To improve outcomes in this subgroup, we investigated the efficacy and safety of fruquintinib in combination with FOLFIRI as a second-line treatment for RAS-mutant mCRC. Methods: This prospective, single-center phase 2 study enrolled patients with RAS-mutant mCRC who had progressed on or were intolerant to first-line treatment. In a 2-week cycle, fruquintinib was administered orally at a daily dose of 3 mg. Irinotecan was administered intravenously at a dose of 180 mg/m² on day 1, leucovorin (LV) was administered intravenously at a dose of 180 mg/m² on day 1, and fluorouracil was administered as an intravenous bolus at 400 mg/m² followed by a continuous infusion of 2400 mg/m² over 46 hours. Tumor assessments were performed every three cycles according to RECIST version 1.1. The primary endpoint was overall response rate (ORR), and secondary endpoints included overall survival (OS), progression-free survival (PFS), duration of response (DoR), and safety. Results: From August 31, 2022, to January 10, 2025, a total of 24 patients were enrolled, including 14 (58%) males with a median age of 59 years (range: 33-79 years), and 17 (71%) patients had an ECOG performance status (PS) of 1. The primary lesion was located in the rectum in 7 (29%) patients, the left-side colon in 11 (46%) patients, and the right-side colon in 6 (25%) patients. The most common metastatic site was liver (83%). For the primary endpoint, 21 patients underwent at least one efficacy assessment. The ORR was 14.3% (3/21), and the disease control rate (DCR) was 90.5% (19/21). With a median follow-up time of 5.1 months (95% CI: 1.6-8.6), the median PFS was 5.0 months (95% CI: 2.9-7.1). OS data were immature. The most common adverse events included leukopenia (67%), neutrophil count decrease (58%), and anemia (54%). The most common grade 3-4 adverse events were neutrophil count decrease (21%), leukopenia (17%), and thrombocytopenia (17%). Gastrointestinal disorders (grade 1-2) occurred in 58% of patients, including nausea, anorexia, and vomiting. Diarrhea occurred in 25% of patients, with 4% being grade 3. Conclusions: The study is ongoing. These preliminary results demonstrate that fruquintinib in combination with FOLFIRI has promising efficacy as a second-line treatment for RAS-mutant metastatic colorectal cancer, with moderate toxicity. Clinical trial information: NCT05522738 .