In the phase III FRESCO-2 trial reported in The Lancet, Dasari et al found that the VEGFR-1,2,3 inhibitor fruquintinib prolonged survival vs placebo in patients with refractory metastatic colorectal cancer.
Study Details
In the double-blind trial, 691 patients from sites in 14 countries were randomly assigned 2:1 between August 2020 and December 2021 to receive fruquintinib at 5 mg (n = 461) or placebo (n = 230) once daily on days 1 to 21 in 28-day cycles, both with best supportive care. Patients had received all current standard approved cytotoxic and targeted therapies, and their disease had progressed on or they were intolerant of trifluridine/tipiracil, regorafenib, or both. Patients had received a median of four lines (interquartile range [IQR] = 3–6 lines) of previous systemic therapy for metastatic disease, with 73% receiving more than three prior lines of therapy. The primary endpoint was overall survival.
Overall Survival
Median follow-up was 11.3 months (IQR = 9.0–14.2 months) in the fruquintinib group and 11.2 months (IQR = 8.7–15.5 months) in the placebo group. Median overall survival was 7.4 months (95% confidence interval [CI] = 6.7–8.2 months) in the fruquintinib group vs 4.8 months (95% CI = 4.0–5.8 months) in the placebo group (hazard ratio [HR] = 0.66, 95% CI = 0.55–0.80, P < .0001); the median overall survival rate at 9 months was 41% vs 28%.
Median progression-free survival was 3.7 months (95% CI = 3.5–3.8 months) in the fruquintinib group vs 1.8 months (95% CI = 1.8–1.9 months) in the placebo group (HR = 0.32, 95% CI = 0.27–0.39, P < .0001). After the end of study treatment, 29% of patients in the fruquintinib group and 34% in the placebo group received additional anticancer therapy during survival follow-up.
Adverse Events
Grade ≥ 3 adverse events occurred in 63% of patients in the fruquintinib group vs 50% of the placebo group; the most common adverse events in the fruquintinib group were hypertension (14% vs 1% in the placebo group), asthenia (8% vs 4%), and hand-foot syndrome (6% vs 0%). Serious adverse events occurred in 38% of each group. Adverse events led to discontinuation of treatment in 20% vs 21% of patients. Treatment-related death occurred in one patient in the fruquintinib group (from intestinal perforation) and one patient in the placebo group (from cardiac arrest).
The investigators concluded: “Fruquintinib treatment resulted in a significant and clinically meaningful benefit in overall survival compared with placebo in patients with refractory metastatic colorectal cancer. These data support the use of fruquintinib as a global treatment option for patients with refractory metastatic colorectal cancer. Ongoing analysis of the quality-of-life data will further establish the clinical benefit of fruquintinib in this patient population.”
Arvind Dasari, MD, of the Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, is the corresponding author of The Lancet article.
Disclosure: The study was funded by HUTCHMED. For full disclosures of the study authors, visit thelancet.com.
