Behind the FDA Approval of Fruquintinib for Previously Treated mCRC

In season 4, episode 18 of Targeted Talks, Arvind Dasari, MD, MS, associate professor in the Department of Gastrointestinal Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston, Texas, dives into the recent approval of fruquintinib for patients with metastatic colorectal cancer (mCRC).

On November 8, 2023, the FDA granted approval to fruquintinib (HMPL-013) for the treatment of patients with mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type and medically appropriate, an anti-EGFR therapy.¹

Dasari explains that fruquintinib is a selective inhibitor of VEGFR-1, -2, and -3. Previously, the agent has inhibited the migration, proliferation, and survival of endothelial cells and also inhibited microvessel formation, tumor cell proliferation, and tumor cell death.

According to Dasari, data from the FRESCO-2 study (NCT04322539) support this regulatory decision. In the phase 3 study, fruquintinib led to a reduction in the risk of death by 34% when given to patients with refractory mCRC. The median overall survival (OS) seen with fruquintinib was 7.4 months compared with 4.8 months with best supportive care in the study. These data represent a significant improvement in OS (HR, 0.66; 95% CI, 0.55-0.80; P < .0001).^2,3

In terms of safety, Dasari highlights some of the adverse events observed in the study, including fatigue, hand-foot syndrome, and issues with liver function tests, but notes that they were rare, reflecting the good toxicity profile of the agent.

With this new approval, Dasari looks forward to the future development of fruquintinib beyond its current indication. He hopes to see the agent move into earlier lines of therapy and given in combination with other drugs to build upon its efficacy.

REFERENCES

1. Takeda receives U.S. FDA approval of FRUZAQLA™ (fruquintinib) for previously treated metastatic colorectal cancer. Takeda. News release. November 8, 2023. Accessed November 8, 2023. https://tinyurl.com/2rkwetvu

2. Dasati NA, Lonardi S, Garcia-Carbonero R, et al. LBA25 - FRESCO-2: A global phase III multiregional clinical trial (MRCT) evaluating the efficacy and safety of fruquintinib in patients with refractory metastatic colorectal cancer. Ann oncol. 2022;33 (suppl_7): S808-S869. doi:10.1016/annonc/annonc1089

3. Dasari A, Lonardi S, Garcia-Carbonero R, et al. Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): an international, multicentre, randomized, double-blind, phase 3 study. Lancet. 2023;402(10395):41-53. doi:10.1016/S0140-6736(23)00772-9