Fruquintinib combined with FOLFIRI/mFOLFOX6 as second-line treatment in patients with RAS-mutant metastatic colorectal cancer (mCRC): A multicenter, open-label, phase II study.

151 Background: Anti-angiogenic drugs combined with chemotherapy could bring good clinical benefit to patients (pts) with mCRC, but the efficacy in pts with RAS mutant mCRC was limited. Fruquintinib is a highly selective oral inhibitor of vascular endothelial growth factor receptors (VEGFRs -1, -2, and -3) and was approved for previously treated mCRC. Our study was to explore the efficacy and safety of fruquintinib combined with FOLFIRI/mFOLFOX6 in the second line treatment of RAS-mutant mCRC (NCT05634590). Methods: Eligible pts with histologically confirmed RAS-mutant mCRC who had received first-line standard chemotherapy regimens were included in the study, and pts received Fru (4 mg, p.o. qd, 3 weeks on/1 week off, q4w) plus FOLFIRI/mFOLFOX6 (d1-15, q4w) until disease progression, unacceptable toxicities, or withdrew consent. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS)and safety. Results: As of Aug 30, 2024, 25 eligible pts were enrolled and received at least one time treatment. Baseline characteristics included median age (66.0 [range: 35-73]), female/male (56.0% / 44.0%), ECOG PS 1(68.0%), left-sided and right-sided colon (72.0% / 28.0%), liver metastasis (64.0%), prior anti-VEGF therapies (76.0%). 14 pts had received at least one tumor assessment. Five pts achieved partial response (PR), 9 pts achieved stable disease (SD), and the ORR was 35.7% (5/14) (95% confidence interval [CI]: 12.8-64.9), the DCR was 100.0% (14/14) (95% CI: 76.8-100.0). Compared to liver metastases, the ORR was higher without liver metastases (42.9% [95%CI 9.9-81.6]). The median PFS was 6.41 months (95% CI: 6.37 - NA), and median OS was not reached yet. In the subgroup analysis, Median PFS was also longer without liver metastases pts than with liver metastases (8.84 mo vs 6.41 mo; HR=1.230; 95%CI 0.2462-6.148; p=0.7775). Additionally, Grade ≥3 treatment-emergent adverse events (TEAEs) included platelet count decreased (18.2%), hypertension (9.1%) and neutrophil count decreased (9.1%). Conclusions: Fruquintinib combined with FOLFIRI/mFOLFOX6 as second-line in patients with RAS-mutant mCRC achieved a promising clinical benefit, with a manageable safety profile. This trial is ongoing and more updated clinical data will be presented in the future. Clinical trial information: NCT05634590 .