Real-world observational study of fruquintinib in combination with irinotecan and capecitabine as second-line treatment in patients with advanced colorectal cancer.

e15539 Background: To improve outcomes for patients with advanced colorectal cancer, chemotherapy can be combined with anti-VEGF and anti-EGFR agents. This study aimed to evaluate the efficacy and safety of fruquintinib in combination with irinotecan and capecitabine as a second-line treatment for patients with advanced colorectal cancer. Methods: This is a prospective, single-arm, real-world observational trial, enrolled patients aged 18 to 75 years with histologically confirmed metastatic colorectal adenocarcinoma. Eligible participants were those with second-line metastatic colorectal adenocarcinoma who had experienced failure with first-line standard therapy (recurrence within six months after the completion of adjuvant chemotherapy was classified as first-line treatment failure). All patients received treatment with fruquintinib (4 mg, po, qd, day 1-14) plus irinotecan (180 mg/m², ivgtt, day 1) (Note: 150 mg/m² for patients with UGT1A1*28 and UGT1A1*6 homozygous or double heterozygous variants) and capecitabine (1000 mg/m², po, bid, day 1-14) of each 21-day cycle. Irinotecan was discontinued after 6–8 cycles. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. An exploratory endpoint assessed changes in biomarkers and their impact on the immune microenvironment during treatment. Results: Between November 10, 2023, and November 20, 2024, 17 patients were enrolled and received treatment. At baseline, the median age was 63 years (range, 54–71 years), and 52.9% of the patients were male. ECOG PS 0/1 was 94.1%(16/17), and the primary tumor site was right-sided colon in 23.5% (4/17), left-side colorectum in 29.4% (5/17), and rectum in 47.0% (8/17). Of the 15 patients who completed at least one efficacy assessment, 1 patient (6.6%) achieved a partial response (PR), 6 patients (40.0%) had stable disease (SD), and 5 patients (33.3%) experienced disease progression (PD). The ORR was 26.7% (95% CI, 4–15), and the DCR was 60.0% (95% CI, 9–15). The median PFS was 9.53 months (95% CI, 7.66–NA). The most frequent grade 3/4 TRAEs were neutropenia (3/17, 17.6%), thrombocytopenia (2/17, 11.8%), and diarrhea (2/17, 11.8%). Conclusions: These results show the preliminary efficacy and safety of fruquintinib in combination with irinotecan and capecitabine as a second-line treatment for patients with advanced colorectal cancer. Clinical trial information: NCT06169202 .