Patients With Refractory Metastatic Colorectal Cancer May Experience Survival Benefits With Fruquintinib

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Targeted therapy with fruquintinib may improve overall survival and progression-free survival  in patients with refractory metastatic colorectal cancer, according to a novel study published by Dasari et al in The Lancet.


According to the American Cancer Society, colorectal cancer is the third leading cause of cancer-related mortality and the second most common cause of cancer mortality among male and female patients combined. Despite treatment advances, patients with metastatic colorectal cancer whose tumors have progressed following several lines of therapy still have poor long-term survival rates of about 4 to 5 months. Therefore, there is a large need for treatment alternatives after current therapies are exhausted.

Fruquintinib is a small-molecule tyrosine kinase inhibitor of the vascular endothelial growth factor receptor (VEGFR). In the phase III FRESCO study, which led to the drug’s approval in China in September 2018, fruquintinib given as third-line therapy or later improved median overall survival in patients with metastatic colorectal cancer compared with placebo (6.6 months vs 9.3 months).

At that time, the standard of care for patients with metastatic colorectal cancer in China differed from that in the United States, the European Union, and Japan. By June 2020, the U.S. Food and Drug Administration granted Fast Track designation to fruquintinib for the treatment of some patients with previously treated colorectal cancer.

“Patients with refractory metastatic colorectal cancer have very limited treatment possibilities and poor outcomes,” explained lead study author Arvind Dasari, MD, Associate Professor of Gastrointestinal Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center. “The results [of the new study] are very encouraging and confirm that fruquintinib may be a novel treatment opportunity for patients who previously had no other options,” he added.

Study Methods and Results

In the double-blind phase III FRESCO-2 trial ( identifier NCT04322539), the researchers randomly assigned 691 patients with advanced refractory metastatic colorectal cancer to either receive oral fruquintinib or placebo—both in combination with supportive care—daily for 3 weeks followed by 1 week of no treatment in 28-day cycles.

The patients were deemed eligible for treatment if they had documented metastatic colorectal cancer and were previously treated with chemotherapy, anti-VEGF therapy, or immune checkpoint inhibitors—if their disease was microsatellite instability–high or mismatch-repair deficient. The patients also had an Eastern Cooperative Oncology Group performance status score of 0 or 1, measurable disease, and expected survival of 12 weeks or more. The primary endpoint was overall survival.

After follow-up, the researchers discovered that compared with those who received placebo, patients who received fruquintinib experienced 7.4 vs 4.8 months of overall survival and 3.7 vs 1.8 months of progression-free survival—representing a statistically significant improvement in outcomes for those in the fruquintinib arm.

Further, the researchers reported that 29.4% of patients in the fruquintinib arm required subsequent anticancer therapies vs 34.3% of those in the placebo arm. The disease control rate was 55.5% for fruquintinib vs 16.1% for placebo.

Grade 3 or 4 treatment-related adverse events occurred in 62.7% of the patients who received fruquintinib—with the most frequent events being hypertension in 13.6%, asthenia in 7.7%, and hand-foot syndrome in 6.4%—and 50.4% of those who received placebo.


“This study supports the meaningful survival improvement and manageable safety profile of fruquintinib,” Dr. Dasari highlighted. “I am excited that this treatment could extend the lives of [patients with] advanced colorectal cancer and preserve their quality of life,” he concluded.

The researchers plan to continue analyzing the quality-of-life data from trial participants who have high tumor burdens and residual side effects from multiple therapies that are known to reduce quality-of-life measures. They expect their ongoing and future studies to explore additional fruquintinib treatment combinations for patients with colorectal cancer.

Disclosure: The research in this study was supported by Hutchison MediPharma Limited. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.