HUTCHMED Announces Phase III FRUTIGA Results in Nature Medicine

HUTCHMED Limited has announced promising results from its Phase III FRUTIGA trial, which investigates the efficacy of combining fruquintinib with paclitaxel in treating second-line advanced gastric cancer in China. These findings were published in Nature Medicine and presented at the American Society of Clinical Oncology (ASCO) 2024 Annual Meeting.

Mechanism and Significance

Fruquintinib is an oral inhibitor targeting vascular endothelial growth factor receptors (VEGFRs) 1, 2, and 3. By blocking tumor angiogenesis, fruquintinib hampers the blood vessel growth vital for cancer progression. Gastric cancer, the fifth most common malignancy worldwide, responds to treatments targeting the VEGFR pathway due to its critical role in the disease's pathogenesis. The FRUTIGA trial's outcomes suggest fruquintinib as a viable therapeutic option for advanced gastric cancer patients.

Trial Design and Results

The FRUTIGA trial was a randomized, double-blind study conducted across 35 sites in China, involving 703 patients with advanced gastric or gastroesophageal junction adenocarcinoma. Participants were divided into two groups: one receiving fruquintinib combined with paclitaxel, and the other receiving paclitaxel monotherapy. The study achieved a positive outcome by demonstrating a statistically significant improvement in progression-free survival (PFS), a primary endpoint. Median PFS for the combination therapy was 5.6 months, compared to 2.7 months for paclitaxel alone (stratified hazard ratio [HR] = 0.569; p < 0.0001). Although an improvement was observed in overall survival (OS) (9.6 months vs. 8.4 months), it was not statistically significant.

The combination therapy showed significant improvements in several secondary endpoints, including objective response rate (ORR), disease control rate (DCR), and duration of response (DoR), and was well tolerated with a consistent safety profile.

Subgroup Analysis and Quality of Life

Further subgroup analysis, presented at ASCO, revealed consistent PFS and OS benefits across different patient segments, particularly in those with intestinal-type cancer and lymph node metastasis. Post-hoc analysis indicated that fruquintinib significantly outperformed placebo in PFS, OS, ORR, DCR, and DoR for patients with lymph node metastasis. This could be attributed to fruquintinib's potent inhibition of VEGFR-3, associated with lymph node metastasis and tumor invasion. Quality of life assessments indicated no adverse impacts compared to standard care, reinforcing the regimen’s viability as a treatment option.

Regulatory and Clinical Developments

Fruquintinib is already approved in China and the United States for treating metastatic colorectal cancer (CRC). A New Drug Application (NDA) for its use in combination with paclitaxel for advanced gastric or gastroesophageal junction adenocarcinoma in China was accepted by the China National Medical Products Administration (NMPA) in April 2023.

About Gastric Cancer and Fruquintinib

Gastric cancer originates in the stomach and is a leading cause of cancer-related deaths worldwide, with significant prevalence in China. Fruquintinib's selective inhibition of VEGFRs is designed to enhance efficacy while minimizing off-target effects, making it a suitable candidate for combination therapies. Co-developed and marketed in China under the brand name ELUNATE® by HUTCHMED and Eli Lilly and Company, fruquintinib has treated over 80,000 colorectal cancer patients as of mid-2023. In the U.S., Takeda markets fruquintinib under the brand name FRUZAQLA®, following approval based on extensive clinical trial data.

About HUTCHMED

HUTCHMED is a biopharmaceutical company focused on the discovery, development, and commercialization of targeted therapies and immunotherapies for cancer and immunological diseases. With a robust pipeline and a global presence, HUTCHMED continues to bring innovative therapies from discovery to market, aiming to improve patient outcomes worldwide.

Conclusion

The FRUTIGA trial's results bolster fruquintinib's potential as a significant treatment for advanced gastric cancer, offering new hope for patients with limited options. Further regulatory reviews and clinical developments are anticipated to expand its therapeutic applications globally.

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