FRESCO-2: Fruquintinib for Patients With Refractory Metastatic Colorectal Cancer

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Researchers reported study results showing that fruquintinib, a small-molecule tyrosine kinase inhibitor of vascular endothelial growth factor receptors (VEGFR), significantly improved overall survival and progression-free survival in patients with refractory metastatic colorectal cancer. Findings from the global FRESCO-2 trial were presented by Dasari et al at the European Society for Medical Oncology (ESMO) Congress 2022 (Abstract LBA25).

The overall survival was 7.4 months for patients treated with fruquintinib vs 4.8 months in the placebo arm, while the median progression-free survival was 3.7 months with fruquintinib compared to 1.8 months in the placebo arm. These results represent a statistically significant improvement relative to controls.

“Patients with refractory metastatic colorectal cancer have very limited treatment possibilities and poor outcomes,” said principal investigator Arvind Dasari, MD, Associate Professor of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center. “These results are very encouraging and confirm that fruquintinib may be a novel treatment opportunity for patients who previously had no other options.”

Study Background

Despite treatment advances, patients with metastatic colorectal cancer still have poor long-term survival rates. After patients show disease progression through several lines of therapy, they typically live only 4 to 5 months. Therefore, there is a large need for treatment alternatives after current therapies are exhausted.

In the original 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 vs 9.3 months). At that time, standard of care for patients with metastatic colorectal cancer in China differed from the United States, the European Union, and Japan. In June 2020, the U.S. Food and Drug Administration granted fast track designation to fruquintinib for the treatment of some previously treated patients with colorectal cancer.

More on FRESCO-2

The randomized phase III FRESCO-2 clinical trial was conducted at 153 sites in the United States, Europe, Japan, and Australia. The double-blind study evaluated treatment with the novel oral therapy fruquintinib plus best supportive care compared to placebo plus best supportive care in heavily pretreated patients with treatment-resistant metastatic colorectal cancer. The primary endpoint was overall survival.

The FRESCO-2 trial randomly assigned 691 patients with advanced refractory metastatic colorectal cancer. Patients were eligible for treatment if they had documented metastatic colorectal cancer and were previously treated either with chemotherapy, anti-VEGF therapy, or immune checkpoint inhibitors (if their disease was microsatellite instability–high or mismatch repair–deficient). Patients had an Eastern Cooperative Oncology Group performance status scale score of 0 or 1, measurable disease, and expected survival of 12 weeks or more.

Patients received either fruquintinib or placebo daily for 3 weeks followed by 1 week off in 28-day cycles. Subsequent anticancer therapies were given to 29.4% of patients in the fruquintinib arm and 34.3% 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 patients in the fruquintinib group and 50.4% in the placebo group. The most frequent events seen in those receiving fruquintinib were hypertension (13.6%), asthenia (7.7%), and hand-foot syndrome (6.4%).

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

The investigators will continue to review quality-of-life data from trial participants, as these patients have high tumor burden and residual side effects from multiple therapies. Ongoing and future studies will explore additional fruquintinib treatment combinations for patients with colorectal cancer.

Disclosure: 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®.