Fruquintinib for Adult Patients With Metastatic Colorectal Cancer

Abstract

Background: Metastatic colorectal cancer (mCRC) represents a major clinical challenge, particularly for refractory patients who have exhausted standard treatments. Fruquintinib is an oral vascular endothelial growth factor receptor (VEGFR) inhibitor that has been approved by FDA for adult patients with mCRC who received prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, vascular endothelial growth factor (VEGF) inhibitor therapy, and an epidermal growth factor receptor targeted therapy if RAS wild type.

Areas of uncertainty: Despite advances in mCRC treatment, patients who progress after standard therapies face limited options. The efficacy of treatments tends to diminish and side effects can be intolerable. There is a need for therapies that can extend survival without worsening quality of life.

Data sources: In the pivotal FRESCO-2 phase 3 trial, 691 patients with heavily pretreated mCRC were studied. Fruquintinib was found to significantly improve survival times, with a median overall survival (OS) of 7.4 months compared with 4.8 months with a placebo. Progression-free survival (PFS) also showed significant improvement with fruquintinib of 3.7 months versus 1.8 months in the placebo group. This was the first trial to show that an oral VEGFR inhibitor can be effective in refractory patients.

Therapeutic advance: Fruquintinib represents a new treatment option for patients with mCRC who have limited therapeutic options. Fruquintinib has demonstrated statistically significant improvements in OS and PFS, in heavily pretreated patients. The FRESCO-2 trial demonstrated its efficacy, even in patients previously treated with trifluridine-tipiracil or regorafenib, showing a 34% reduction in OS and improved PFS.

Conclusions: Fruquintinib, approved by FDA for heavily pretreated patients with mCRC, addresses an unmet need in this population. Future research should focus on optimizing its integration into treatment plans and identifying biomarkers for personalized therapy.

Keywords: VEGFR 1-2-3; angiogenesis; checkpoint inhibitor; chemorefractory; colon cancer therapy; colorectal cancer; fruquitinib; immunotherapy; peritoneal metastasis; tyrosine kinase inhibitors.