Fruquintinib Approved for Refractory Metastatic Colorectal Cancer

Colorectal cancer.

The FDA has approved fruquintinib (Fruzaqla™, Takeda Pharmaceuticals, Inc.) for adult patients with metastatic colorectal cancer (mCRC) who received prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti–vascular endothelial growth factor (VEGF) therapy, and, if rat sarcoma (RAS) wild-type and medically appropriate, an anti–endothelial growth factor receptor (EGFR) therapy. This is the first approval of fruquintinib in the United States.  

Why it matters: “There is a paucity of effective systemic therapy options for patients with advanced, chemotherapy-refractory CRC,” wrote Arvind Dasari, MD, MS, an Associate Professor in the Department of Gastrointestinal Medical Oncology at MD Anderson Cancer Center, and colleagues, in their published results of the FRESCO-2 trial (NCT04322539), on which approval was based. “We aimed to evaluate the efficacy and safety of fruquintinib, a highly selective and potent oral inhibitor of VEGFRs 1, 2, and 3, in patients with heavily pretreated mCRC.”

What they studied: Safety and efficacy were studied in two clinical trials: FRESCO-2 and FRESCO (NCT02314819).

FRESCO-2 was a phase 3, multicenter, international, double-blind, placebo-controlled trial which enrolled 691 patients with mCRC who had disease progression during or after prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF biological therapy, an anti-EGFR biological therapy if RAS wild-type, and either trifluridine/tipiracil or regorafenib or both.

FRESCO was a phase 3, multicenter, double-blind, placebo-controlled trial, conducted in China, which enrolled 416 patients with mCRC who had disease progression during or after prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

Both trials randomized patients 2:1 to receive either 5 mg of fruquintinib orally, once daily, or placebo, for the first 21 days of each 28-day cycle in addition to the best supportive care. Treatment was continued until disease progression or unacceptable toxicity.

The primary end point measured in both trials was overall survival.

What they found: Both trials produced statistically significant and clinically meaningful results with fruquintinib. FRESCO-2 saw a median overall survival of 7.4 months with fruquintinib compared a median of 4.8 months in the placebo arm. FRESCO saw a median overall survival of 9.3 months with fruquintinib compared with a median of 6.6 months in the placebo arm.

What’s next: Further evaluation of fruquintinib’s quality of life data to establish its clinical benefit is currently ongoing.

Adverse events: The most common adverse events in ≥20% of patients were hypertension, palmar-plantar erythrodysesthesia, proteinuria, dysphonia, abdominal pain, diarrhea, and asthenia.

Conclusion: “Fruquintinib treatment resulted in a significant and clinically meaningful benefit in overall survival compared with placebo in patients with refractory mCRC,” concluded Dr. Dasari and colleagues. “These data support the use of fruquintinib as a global treatment option for patients with refractory mCRC.”

“The treatment-related, treatment-emergent adverse event (TEAE) profile of fruquintinib in Chinese patents with mCRC was comparable among different subgroups and consistent with that reported in the overall population,” concluded Jin Li, MD, PhD, Director of the Department of Oncology at Tongji University, Shanghai East Hospital in China, and colleagues, in their publication of the FRESCO trial.

Instructions: The recommended dosage of fruquintinib is 5 mg orally, once daily, with or without food, for the first 21 days of each 28-day cycle until disease progression or unacceptable toxicity.

For More Information

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

Li J, Qin S, Xu RH, et al (2018). Effect of fruquintinib vs placebo on overall survival in patients with previously treated metastatic colorectal cancer: the FRESCO randomized clinical trial. JAMA, 319(24):2486-2496. DOI:10.1001/jama.2018.7855

Li J, Guo W, Bai Y, et al (2020). Safety profile and adverse events of special interest for fruquintinib in Chinese patients with previously treated metastatic colorectal cancer: analysis of the phase 3 FRESCO trial. Adv Ther, 37(11):4585-4598. DOI:10.1007/s12325-020-01477-w

Clinicaltrials.gov (2023). A study of efficacy and safety of fruquintinib (HMPL-013) in participants with metastatic colorectal cancer (FRESCO-2). NLM identifier: NCT04322539.

Clinicaltrials.gov (2020). A phase 3 trial evaluating fruquintinib efficacy and safety in 3+ line colorectal cancer patients (FRESCO). NLM identifier: NCT02314819.

Fruzaqla™ (fruquintinib) prescribing information (2023). Takeda Pharmaceuticals, Inc. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217564s000lbl.pdf

US Food and Drug Administration (2023). FDA approves fruquintinib in refractory metastatic colorectal cancer. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-fruquintinib-refractory-metastatic-colorectal-cancer

Image credit: Patho. Licensed under CC BY-SA 3.0 DEED


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