Health Canada Green Lights Fruquintinib for Metastatic Colorectal Cancer

Health Canada has approved fruquintinib (Fruzaqla) for the treatment of adult patients with metastatic colorectal cancer (mCRC) who have been previously treated with or are not considered candidates for available standard therapies, including fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy; an anti-VEGF agent; an anti-EGFR agent for those with RAS wild-type disease; and either trifluridine-tipiracil (TAS-102; Lonsurf) or regorafenib (Stivarga).1

The regulatory decision was supported by data from the phase 3 FRESCO-2 (NCT04322539) and FRESCO (NCT02314819) trials.

“We welcome Health Canada’s authorization of [fruquintinib]. Knowing that there is a new therapy available will provide hope to patients and their families who have been waiting for new therapeutic options. This new treatment provides an additional opportunity for Canadians with mCRC to slow disease progression,” Barry D. Stein, president and CEO of Colorectal Cancer Canada, stated in a news release.

In November 2023, the FDA approved fruquintinib for the treatment of adult 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.2 This approval was also supported by data from FRESCO-2 and FRESCO.

FRESCO-2 Data

Findings from the international, randomized, double-blind, placebo-controlled FRESCO-2 trial showed that patients randomly assigned to receive fruquintinib (n = 461) experienced a median overall survival (OS) of 7.4 months (95% CI, 6.7-8.2) vs 4.8 months (95% CI, 4.0-5.8) for those randomly assigned to the placebo group (n = 230; HR, 0.66; 95% CI, 0.55-0.80; P < .0001).3

Regarding safety, grade 3 or higher adverse effects (AEs) were reported in 63% of patients who received fruquintinib (n = 456) and 50% of those given placebo (n = 230). The most common grade 3 or higher AEs experienced by patients treated with fruquintinib included hypertension (14%), asthenia (8%), and hand-foot syndrome (6%). One treatment-related death occurred in each group; intestinal perforation led to death in 1 patient in the fruquintinib group, and cardiac arrest led to death in 1 patient in the placebo group.

Investigators enrolled patients at least 18 years of age (or at least 20 years of age in Japan) with histologically or cytologically documented mCRC who had previously received all standard, approved cytotoxic and targeted therapies. Disease progression on or intolerance to TAS-102, regorafenib, or both was required.

Patients were randomly assigned 2:1 to receive fruquintinib at 5 mg or matching placebo once per day on days 1 to 21 of each 28-day cycle. Best supportive care was also given to patients in both arms. Treatment continued until disease progression, death, unacceptable toxicity, withdrawal of consent, discontinuation by the physician, or study completion or termination.

OS served as the trial’s primary end point. Secondary end points included progression-free survival (PFS) per RECIST 1.1 criteria, objective response rate (ORR), disease control rate (DCR), duration of response, and safety.

FRESCO Findings

Data from the randomized, double-blind, placebo-controlled, multicenter trial conducted in China showed that patients randomly assigned to receive fruquintinib (n = 278) experienced a median OS of 9.3 months (95% CI, 8.2-10.5) vs 6.6 months (95% CI, 5.9-8.1) for those randomly assigned to the placebo arm (n = 138; HR, 0.65; 95% CI, 0.51-0.83; P < .001).4 The median PFS was 3.7 months (95% CI, 3.7-4.6) in the fruquintinib arm vs 1.8 months (95% CI, 1.8-1.8) in the placebo arm (HR, 0.26; 95% CI, 0.21 to 0.34; P < .001).

Safety findings showed that grade 3/4 treatment-emergent AEs occurred in 61.2% of patients treated with fruquintinib vs 19.7% of patients given placebo. The rates of serious AEs were 15.5% and 5.8%, respectively. Hospitalization was required for 14.4% of patients in the fruquintinib arm vs 5.1% of patients in the placebo arm.

The study included patients 18 to 75 years of age with mCRC whose disease had progressed after at least 2 lines of chemotherapy and who were naive to a VEGFR inhibitor.

Patients were randomly assigned 2:1 to receive fruquintinib at 5 mg or placebo once per day on days 1 to 21 of each 28-day cycle.

OS was the trial’s primary end point. Secondary end points included PFS, ORR, DCR, and safety.

“Fruquintinib represents a new option in the treatment of mCRC. This therapy aims to slow disease progression, with the potential to help extend survival,” Hatim Karachiwala, MD, a medical oncologist at the Tom Baker Cancer Centre in Calgary, Alberta, added in the news release.1

References

1. Takeda’s Fruzaqla (fruquintinib) receives Health Canada market authorization for metastatic colorectal cancer (mCRC). News release. Takeda. January 20, 2025. Accessed January 20, 2025. https://www.biospace.com/press-releases/takedas-fruzaqla-fruquintinib-receives-health-canada-market-authorization-for-metastatic-colorectal-cancer-mcrc
2. FDA approves fruquintinib in refractory metastatic colorectal cancer. FDA. November 8, 2023. Accessed January 20, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-fruquintinib-refractory-metastatic-colorectal-cancer
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, randomised, double-blind, phase 3 study. Lancet. 2023;402(10395):41-53. doi:10.1016/S0140-6736(23)00772-9
4. Li J, Qin S, Xu RH, et al. Effect of fruquintinib vs placebo on overall survival in patients with previously treated metastatic colorectal cancer: the FRESCO randomized clinical trial. JAMA. 2018;319(24):2486-2496. doi:10.1001/jama.2018.7855