Fruquintinib alternating with bevacizumab plus capecitabine as maintenance therapy after first-line treatment in metastatic colorectal cancer (mCRC): A multicenter, open-label, phase II study.

Abstract

e15539 Background: Maintenance therapy with bevacizumab (Bev) plus capecitabine (Cap) is recommended to unresectable mCRC patients (pts). Fruquintinib (Fru) is a highly selective TKI that inhibits vascular endothelial growth factor receptor (VEGFR)-1,2,3. This study is to compare the therapeutic potential of alternating treatment with fruquintinib and bevacizumab plus capecitabine as maintenance therapy for mCRC (NCT05659290). Here, we report the updated results. Methods: Eligible mCRC pts aged 18-75 years with stable disease or better after induction treatment with chemotherapy in combination with Bev, ECOG PS 0-2, adequate bone marrow, liver, and renal function were enrolled. Sixty-one patients were included (20 in Phase Ⅱa, 41 in Phase Ⅱb). In Phase IIa, pts were orally administered with Fru (3~5 mg, qd, d1-14, q3w) alternating with Bev (7.5 mg/kg, iv.gtt, d1, q3w) plus Cap (850 mg/m 2 , orally, twice daily, d1-14, q3w). In Phase Ⅱb, pts were randomly assigned (1:1) to either maintenance treatment with Fru (3 mg, qd, d1-14, q3w) alternating with Bev plus Cap or Bev plus Cap. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR) and safety. Results: As of December 2025, in Phase Ⅱa (n = 20), the median PFS was 8.25 months ( 95% CI: 5.78-NA). PFS tended to be longer in patients with liver metastases compared to those without liver metastases (8.28 vs 4.80 months; p = 0.08), and in patients with left-sided tumors versus right-sided tumors (8.28 vs 4.48 months; p = 0.70).In Phase Ⅱb, patients were randomized to receive Fruquintinib + Bevacizumab + Capecitabine (Fru+Bev+Cap, n = 21) or Bevacizumab + Capecitabine (Bev+Cap, n = 20). The median ages were 60 (range 25–73) and 58 years (range 46–75), respectively. Baseline characteristics included left-sided primary tumors (57.1% vs 85.0%), liver metastases (71.4% vs 30.0%), and ≥2 metastatic sites (66.7% vs 60.0%). Thirty-five patients had undergone at least one tumor assessment. Median PFS was not mature in the Fru+Bev+Cap arm and was 8.18 months in the Bev+Cap arm (p = 0.30). The ORR was 6.25% versus 5.26%, and the DCR was 81.3% versus 73.7%, respectively. The most common treatment-emergent adverse events (TEAEs) in the Fru+Bev+Cap arm were hypertension (57.1%), proteinuria (42.9%), and decreased platelet count (23.8%). In the Bev+Cap arm, the most common TEAEs were hypertension (50.0%), hyperuricemia (35.0%), and decreased platelet count (20.0%). Conclusions: Fruquintinib alternating with bevacizumab plus capecitabine as maintenance therapy after first-line treatment in mCRC demonstrated promising antitumor activity and manageable toxicity. The ongoing Phase IIb trial warrants further investigation in this patient population. Clinical trial information: NCT05659290 .