Japan’s MHLW Approves Fruquintinib in Pretreated mCRC After Chemotherapy

Japan’s Ministry of Health, Labour, and Welfare (MHLW) has approved fruquintinib (Fruzaqla) for the treatment of patients with unresectable metastatic colorectal cancer (mCRC) who have experienced disease progression following chemotherapy. The regulatory decision marks the first novel targeted therapy approved for mCRC regardless of biomarker status in Japan in more than 10 years.¹

The approval was primarily supported by findings from the phase 3 FRESCO-2 trial (NCT04322539). Data from the study published in The Lancet demonstrated that at a median follow-up of 11.3 months (interquartile range [IQR], 9.0-14.2) in the fruquintinib group (n = 461) and 11.2 months (IQR, 8.7-15.5) in the placebo arm (n = 230), the median overall survival (OS) was 7.4 months (95% CI, 6.7-8.2) vs 4.8 months (95% CI, 4.0-5.8), respectively (HR 0.66; 95% CI, 0.55-0.80; P < .0001). The median progression-free survival (PFS) was 3.7 months (95% CI, 3.5-3.8) vs 1.8 months (95% CI, 1.8-1.9), respectively (HR, 0.32; 95% CI, 0.27-0.39; P < .0001).²

“Takeda has now obtained approval in Japan for fruquintinib demonstrating the strength of our global data package and the potential of this novel medicine to provide a much-needed treatment option to patients with mCRC,” Weiguo Su, PhD, chief executive officer and chief scientific officer of HUTCHMED, stated in a news release.¹ “Takeda has been a leader in mCRC treatment in Japan for over a decade, and we are confident that it is well placed to bring fruquintinib to patients in Japan.”

In November 2023, the FDA approved fruquintinib for the treatment of adult patients with mCRC who previously received luoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type and medically appropriate, an anti-EGFR therapy. The agent is also approved for patients with mCRC in China and Europe.^1,3

FRESCO-2 was an international, double-blind, placebo-controlled study that enrolled patients at least 18 years of age (or at least 20 years of age in Japan) with histologically or cytologically documented metastatic colorectal adenocarcinoma who were previously treated with all current standard approved cytotoxic and targeted therapies, and experienced disease progression on or were unable to receive trifluridine/tipiracil (Lonsurf), regorafenib (Stivarga), or both. In order to be eligible for the study, patients also needed to have an ECOG performance status of 1 or less and measurable disease per RECIST 1.1 criteria. Those with mismatch repair or microsatellite instability-high disease also needed to have received an immune-checkpoint inhibitor, and patients with BRAF V600E–mutant disease needed to have received a BRAF inhibitor, if available.²

After enrollment, patients were randomly assigned 2:1 to receive fruquintinib at 5 mg or matched placebo orally once per day on days 1 through 21 in 28-day cycles, both in combination with best supportive care. The primary end point was OS. PFS was a key secondary end point; other secondary end points included objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and safety.

Additional findings from FRESCO-2 showed that the ORRs in the fruquintinib and placebo arms were 2% (95% CI, 0.6%-3.1%) vs 0% (95% CI, 0.0%-1.6%), respectively. The DCRs were 56% (95% CI, 50.9%-60.1%) vs 16% (95% CI, 11.6%-21.5%), respectively. The median DOR was 10.7 months (95% CI, 3.9–not estimable) in the fruquintinib and was 0 months in the placebo arm.

In terms of safety, patients in the investigational and placebo arms experienced any-grade adverse effects (AEs) at rates of 99% vs 93%, respectively. Common any-grade AEs included hypertension (37% vs 9%), asthenia (34% vs 23%), and decreased appetite (27% vs 17%). AEs leading to death occurred in 11% compared with 20%, respectively.

“The approval of fruquintinib in Japan is significant news for patients with mCRC, who have long needed additional effective treatment options,”Takayuki Yoshino, MD, PhD, deputy director of hospital, head, Division for the Promotion of Drug and Diagnostic Development, and chief, Department of Gastrointestinal Oncology, National Cancer Center Hospital East, in Kashiwa, Japan, added in the news release.¹ “The global FRESCO-2 study demonstrated the impact that this treatment can have on patients in the clinic. The increasing availability of screening and effective therapies in Japan has been driving patient outcomes in colorectal cancer, and we hope the introduction of fruquintinib will offer new hope to those with the condition.”

References

1. HUTCHMED announces Japan approval for Fruzaqla (fruquintinib) received by Takeda. News release. HUTCHMED. September 24, 2024. Accessed September 24, 2024. https://www.hutch-med.com/japan-approval-for-fruzaqla-fruquintinib/
2. 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
3. FDA approves fruquintinib in refractory metastatic colorectal cancer. FDA. November 8, 2023. Accessed September 24, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-fruquintinib-refractory-metastatic-colorectal-cancer