A randomized phase II trial of fruquintinib plus capecitabine versus capecitabine alone as maintenance therapy following first-line chemotherapy in metastatic colorectal cancer (mCRC).

3534 Background: Maintenance therapy with capecitabine (Cap) is widely recommended to unresectable mCRC patients (pts). Fruquintinib (Fru) is a highly selective inhibitor of VEGFR1/2/3. We sought to compare the therapeutic potential of Fru plus Cap versus Cap as maintenance therapy for mCRC. Methods: Eligible pts with histologically confirmed mCRC who achieved disease control (including CR/PR and SD) after at least six cycles of first-line standard chemotherapy were included in the study. During phase Ib, pts received Fru (4 mg, p.o. qd, 3 weeks on/1 week off, q4w) plus Cap (850 mg/m 2 , p.o. bid, d1-7 and d15-21, q4w). In phase II, pts were randomized in a 1:1 ratio to receive either Fru (RP2D, 3mg, 3 weeks on/1 week off) plus Cap or Cap alone. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR) and safety. Results: As of November 15, 2025, 113 eligible patients were enrolled, including 6 in phase Ib and 107 in phase II. In this presentation, we report only the updated data from Phase II. 107 were randomly assigned to receive either fruquintinib plus capecitabine (Fru+Cap; n=52) or capecitabine alone (Cap; n=55). Baseline characteristics included median age: 61 years (range, 30-78) vs. 60 years (range, 31-80), male: 51.9% vs. 58.2%, left-sided colorectal primary tumors: 55.8% vs. 61.8% and RAS-mutant tumors: 53.8% vs. 52.7%. As first-line maintenance therapy, the median PFS1 (defined as time from randomization to disease progression or death) in the per-protocol population was 6.03 months with Fru+Cap versus 3.30 months with Cap (p=0.003). Furthermore, the Fru+Cap arm demonstrated significantly prolonged PFS2 (defined as the time from first receipt of first-line treatment to disease progression or death): 12.1 vs. 9.7 months, p=0.006. Consistent improvements were observed in objective response rate (ORR: 14.6% vs. 7.0%) and disease control rate (DCR: 75.6% vs. 51.2%). Grade ≥3 treatment-emergent adverse events (TEAEs) in Fru+Cap arm included hypertension (5.77%), palmar-plantar erythrodysesthesia syndrome (1.9%) and albuminuria (1.9%). Diarrhea (3.64%), palmar-plantar erythrodysesthesia syndrome (1.8%) and oral mucositis (1.8%) were the most frequently reported grade ≥3 TEAEs in Cap arm. Conclusions: PFS was significantly prolonged and ORR was improved in mCRC pts treated with Fru plus Cap as first-line maintenance treatment. The safety profile of the combination regimen was manageable and aligned with the expected toxicity patterns of the individual agents. Clinical trial information: NCT05451719 .