Li J, et al. - Experts assessed the effectiveness and safety of oral fruquintinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, as third-line or later therapy in patients with metastatic colorectal cancer (CRC). A statistically significant increase in overall survival was resulted by oral fruquintinib vs placebo, among Chinese patients with metastatic CRC who had tumor progression after at least 2 prior chemotherapy regimens.

Methods

• Experts conducted FRESCO (Fruquintinib Efficacy and Safety in 3+ Line Colorectal Cancer Patients) a randomized, double-blind, placebo-controlled, multicenter, phase 3 clinical trial.
• Screening was conducted from December 2014 to May 2016 among 519 patients aged 18 to 75 years who had metastatic CRC that progressed after at least 2 lines of chemotherapy, but had not received VEGFR inhibitor therapy; 416 met the eligibility criteria and were stratified by prior anti-VEGF therapy and K-ras status.
• January 17, 2017 was the final date of follow-up.
• They randomly allocated patients in a 2:1 ratio to receive either fruquintinib, 5 mg (n=278) or placebo (n=138) orally, once daily for 21 days, followed by 7 days off in 28-day cycles, until disease progression, intolerable toxicity, or study withdrawal.
• Overall survival was the primary end point.
• Progression-free survival (time from randomization to disease progression or death), objective response rate (confirmed complete or partial response), and disease control rate (complete or partial response, or stable disease recorded ≥8 weeks post-randomization) were the key secondary efficacy endpoints.
• They also assessed the duration of response.
• Treatment-emergent adverse events were included in the safety outcomes.

Results

• As per data, out of the 416 randomized patients (mean age, 54.6 years; 161 [38.7%] women), 404 (97.1%) completed the trial.
• Findings suggested that, with fruquintinib, the median overall survival was significantly prolonged vs placebo (9.3 months [95% CI, 8.2-10.5] vs 6.6 months [95% CI, 5.9-8.1]); hazard ratio (HR) for death, 0.65 (95% CI, 0.51-0.83; P < .001).
• They noted a significant increase in the median progression-free survival with fruquintinib (3.7 months [95% CI, 3.7-4.6] vs 1.8 months [95% CI, 1.8-1.8] months); with a HR for progression or death of 0.26 (95% CI, 0.21 to 0.34; P < .001).