Fruquintinib Approved in Japan for Unresectable Advanced or Recurrent CRC

This approval follows the 2023 FDA approval of fruquintinib for patients with metastatic CRC who have previously received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy plus anti-VEGF therapy, as well as patients with RAS wild-type disease who have received anti-EGFR therapy.

Fruquintinib (Fruzaqla) has been approved by the Japanese Ministry of Health, Labour and Welfare for the treatment of advanced or recurrent colorectal cancer (CRC) that is not curable nor resectable following progression after chemotherapy, according to a press release from Takeda.¹

The approval is based on results of the global phase 3 FRESCO-2 (NCT04322539) trial, which compared fruquintinib plus best supportive care with placebo plus best supportive care in patients with previously treated metastatic CRC.

“Although the mortality rate of CRC has been going down in recent years due to early screening and advances in treatment, the 5-year survival rate for metastatic CRC remains low and new treatment options are much in need,” Takayuki Yoshino, MD, PhD, deputy director of Hospital, head of the Division for the Promotion of Drug and Diagnostic Development, and chief of the Department of Gastrointestinal Oncology at the National Cancer Center Hospital East, in Kashiwa Japan, who served on the FRESCO-2 study steering committee, stated in the press release.¹ “The approval of [fruquintinib] in Japan offers new hope for patients and families of patients with metastatic CRC, as well as for health care personnel involved in CRC treatment. I feel that it is of great clinical significance.”

A total of 691 patients were enrolled and randomly assigned 2:1 to receive either fruquintinib (n = 461) or placebo (n = 230). Prior to enrollment on the study, patients had received a median of 4 lines (IQR, 3-6) of previous systemic therapy for metastatic CRC. Of the 691 patients, 502 (73%) had received more than 3 lines of therapy.

In the FRESCO-2 study, the median patient age was 64 years. Liver metastases were present in 72% of patients, and 63% of patients had RAS mutations. A prior history of anti-VEGF treatment was observed in 96% of patients, and 39% had previously received anti-EGFR therapy.

The median progression-free survival was 3.7 months (95% CI, 3.5-3.8) in the fruquintinib arm vs 1.8 months (95% CI, 1.8-1.9) in the placebo arm (HR, 0.32; 95% CI, 0.27-0.39; P <.0001). The median overall survival was 7.4 months (95% CI, (95% CI, 6.7-8.2) in the fruquintinib arm and 4.8 months (95% CI, 4.0-5.8) in the best supportive care arm (HR, 0.66; 95% CI, 0.55-0.80; P <.0001).

Grade 3 or higher adverse effects (AEs) were observed in 286 (63%) of 456 patients in the fruquintinib arm and 116 (50%) of 230 patients in the placebo arm. The most common were hypertension (14%), asthenia (8%), and hand-foot syndrome (6%).

FRESCO-2 was an international, randomized, double-blind study conducted at 124 hospitals and cancer centers across 14 countries. Patients were required to be 18 years or older (20 years or older in Japan) with histologically or cytologically documented metastatic colorectal adenocarcinoma following all standard approved cytotoxic and targeted therapies, and to have progressed on or were intolerant to trifluridine-tipiracil (Lonsurf), regorafenib (Stivarga), or both. Patients received fruquintinib 5 mg or matched placebo on days 1-21 in 28-day cycles plus supportive care. The primary end point was overall survival.

This approval follows the 2023 FDA approval of fruquintinib for patients with metastatic CRC who have previously received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy plus anti-VEGF therapy, as well as patients with RAS wild-type disease who have received anti-EGFR therapy.

“With this approval of [fruquintinib], we are able to further support patients living with this debilitating disease,” Teresa Bitetti, president of the global oncology business unit at Takeda, stated in the press release.¹ “Fruzaqla is now approved in the US, European Union, Japan, and a number of other countries around the world, and we remain committed to bringing this treatment to additional patients with metastatic CRC around the world who urgently need new therapeutic options.”

References

1. Takeda receives approval for FRUZAQLA (fruquintinib) in Japan for the treatment of unresectable advanced or recurrent colorectal cancer. News release. Takeda. September 24, 2024. Accessed September 24, 2024. https://tinyurl.com/yckbwjrk
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. Published online June 15, 2023. doi:10.1016/S0140-6736(23)00772-9