Efficacy and safety of 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.

166 Background: Maintenance therapy with bevacizumab (Bev) plus capecitabine (Cap) is widely 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). 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. Forty patients were included (20 in phase IIa, 40 in phase IIb). In phase IIa, pts were orally administered with Fru (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 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: At cutoff date of Sep 5, 2024, In phase IIa, 20 pts (14 males and 6 females) were enrolled with the median age was 59.0 years (range 27-75), ECOG PS 1 (95.0%), liver metastasis (55.0%), left-sided colon and rectal primary (70.0%). 11 pts had received at least one tumor assessment. the DCR was 100.0% (11/11) and the mPFS was immature, but 4 pts showed the PFS of ≥ 8 months (8.3, 8.6, 9.2, 13.4 m, respectively). The most common treatment-emergent adverse events (TEAEs) were proteinuria (60.0%), hypoalbuminemia (40.0%), hypertension (35.0%); The most common grade ≥ 3 adverse events were hypertension (10.0%), proteinuria (5.0%), and platelet count decreased (5.0%). After fully considering about patient′s tolerance and safety, the phase IIb of Fru was adjusted from 5mg to 3mg, these results provided further evidence that 3mg can ensure the safety and tolerance. Conclusions: Fruquintinib alternating with bevacizumab plus capecitabine as maintenance therapy after first-line treatment in mCRC showed preliminary anti-tumor activity and manageable toxicity. The phase IIb is ongoing and warrants further exploration in mCRC. Clinical trial information: NCT05659290 .