HUTCHMED (China) Limited announced results from FRUTIGA, HUTCHMED's Phase III trial of fruquintinib in combination with paclitaxel for the treatment of second-line advanced gastric cancer in China. Updated efficacy data in key subgroups and data on quality of life (QoL) within this publication were also presented on June 1 at the American Society of Clinical Oncology (ASCO") 2024 Annual Meeting. Fruquintinib is a selective oral inhibitor of vascular endothelial growth factor receptors (VEGFRs") 1, 2 and 3. It works as an anti-cancer therapy by blocking tumor angiogenesis, a proliferation of blood vessels that is critical for cancer growth.

The VEGFR pathway plays a key role in the pathogenesis of gastric cancer, which is the fifth most common malignant cancer worldwide, with 1.1 million new cases per year. The FRUTIGA trial results published by Nature Medicine suggest that fruquintinib could be another effective treatment option for gastric cancer patients. FRUTIGA was a 1:1 randomized, double-blind, Phase III study conducted across 35 sites in China (NCT03223376).

It evaluated fruquintinib in combination with paclitaxel chemotherapy, compared with paclitaxel monotherapy, for second-line treatment in 703 patients with advanced gastric or gastroesophageal junction adenocarcinoma. The study was declared positive due to a statistically significant improvement in progression-free survival (PFS"), one of two dual primary endpoints. Median PFS for patients who received fruquintinib plus paclitaxel was 5.6 months, compared to 2.7 months for those who received paclitaxel monotherapy (stratified hazard ratio [ HR"] = 0.569; p < 0.0001).

An improvement was also observed in the dual primary endpoint of median overall survival (OS"), (9.6 months vs. 8.4 months) but this was not statistically significant. Fruquintinib plus paclitaxel demonstrated statistically significant improvements in multiple other endpoints including objective response rate (ORR"), disease control rate (DCR) and duration of response (DoR).

It was well tolerated, with a safety profile consistent with expectations and previously reported studies. In further analysis of key subgroups presented at ASCO, PFS and OS results were consistent with the primary analysis compared to the intention-to-treat (ITT) population. There was a clear PFS benefit observed for fruquintinib plus paclitaxel in the majority of subgroups, with particular benefit in both PFS and OS in the intestinal-type and lymph node metastasis subgroups.

An exploratory post-hoc analysis for patients with lymph node metastasis revealed superior benefits of fruquintinib versus placebo in PFS, OS, ORR, disease control rate and duration of response. A possible mechanism for this effect is fruquintinib's potent inhibition of VEGFR -3, which is closely linked to lymph node metastasis and tumor invasion. Further analysis of patient-reported quality of life (QoL") revealed no adverse impact on QoL at end of treatment compared to current standard of care.

Together, these additional findings, alongside previously reported results, support fruquintinib plus paclitaxel as another treatment option in this indication. Key results from FRUTIGA were previously disclosed at the American Society of Clinical Oncology (ASCO) Plenary Series Session on February 6, 2024.