The combination of fruquintinib and paclitaxel is a potential new second-line treatment for patients with advanced gastric or gastroesophageal junction cancer, according to data presented during the ASCO Plenary Series: February 2024 Session (Abstract 438780).
Results of the phase III FRUTIGA study, which was conducted in China, showed significantly improved progression-free survival in patients with advanced gastroesophageal junction adenocarcinoma treated with the novel combination compared to paclitaxel alone (5.55 months vs 2.73 months), particularly in patients with lymph node metastases. A higher response rate was also observed in the experimental arm compared with the control arm (42.5% vs 22.4%).
Authors of the study emphasized that this is the first phase III trial to demonstrate survival benefits with a new treatment alternative to ramucirumab-containing therapy in the second-line setting for advanced gastric or gastroesophageal junction adenocarcinoma.
“The positive results of FRUTIGA further enrich the evidence for the effectiveness of the VEGFR signaling pathway acting on advanced gastric/gastroesophageal adenocarcinoma, which had been previously supported by the efficacy of ramucirumab,” said lead study author Rui-Hua Xu, MD, PhD, of Sun Yat-sen University Cancer Center in Guangzhou, China. “Fruquintinib plus paclitaxel could be a promising second-line treatment option for patients with advanced gastric/gastroesophageal adenocarcinoma that progressed on first-line chemotherapy.”
Rui-Hua Xu, MD, PhD
As Dr. Xu reported, epidemiology data from 2021 show that approximately 49.5% of patients with gastric or gastroesophageal junction adenocarcinoma receive second-line treatment. However, treatment options are limited, representing an urgent medical need.
Fruquintinib, a highly selective and potent oral vascular endothelial growth factor (VEGF) receptor inhibitor of VEGFR 1, 2, and 3, is already approved in the United States and China for third- and later-line treatments of patients with metastatic colorectal cancer based on data from the FRESCO trial demonstrating significantly improved overall survival.
According to Dr. Xu, blocking VEGF receptors stops the formation of new blood vessels that are used to deliver nutrients needed for a tumor to grow and spread, essentially “starving” the tumor.
FRUTIGA Study Design
The FRUTIGA trial evaluated the efficacy and safety of fruquintinib plus paclitaxel vs placebo plus paclitaxel in patients with advanced gastric or gastroesophageal junction adenocarcinoma that progressed on fluoropyrimidine- or platinum-containing first-line chemotherapy. The dual primary endpoints of the study were progression-free and overall survival.
Dr. Xu and colleagues enrolled 703 patients in the study, with 699 patients receiving at least one dose of fruquintinib. Although patient demographics were well balanced in both study arms, Dr. Xu noted an imbalance of patients receiving subsequent antitumor therapies across the two groups (52.7% in the fruquintinib plus paclitaxel group vs 72.2% in the placebo plus paclitaxel group).
Higher Response Rates and Improved Survival
As Dr. Xu reported, the combination of fruquintinib and paclitaxel fulfilled the primary endpoint of progression-free survival vs paclitaxel and placebo in patients with advanced gastric or gastroesophageal junction adenocarcinoma. Progression-free survival in the fruquintinib group was more than two-fold higher than the placebo group (5.55 months vs 2.73 months, respectively).
After a median follow-up of 31.7 months, median overall survival was also higher in the fruquintinib and paclitaxel arm compared to the control arm (9.63 months vs 8.41 months), but this difference was not statistically significant. After adjusting for subsequent antitumor therapies, post hoc analyses showed a nominal statistically significant improvement in overall survival in the fruquintinib plus paclitaxel group.
Dr. Xu also noted that median progression-free survival was even more prolonged among patients with lymph node metastases and nondiffuse gastric/gastroesophageal adenocarcinoma (6.08 months in the fruquintinib group vs 2.69 months in the placebo group), and overall survival showed a nominal statistically significant improvement as well (9.56 months vs 7.85 months).
According to Dr. Xu, similar rates of treatment-emergent adverse events were observed in both groups. However, the incidence of grade 3 or higher serious events was higher in patients receiving fruquintinib. The most common treatment-emergent adverse events of grade 3 or higher were neutropenia (60.0% vs 36.4%), leukopenia (42.9% vs 23.5%), and anemia (11.7% vs 10.6%).
“Although chemotherapy-induced cardiac toxicity was higher in the fruquintinib group, most events were well controlled with active clinical intervention and management,” said Dr. Xu. “These results confirm the potential of fruquintinib and paclitaxel in improving the prognosis for this patient demographic.”
Disclosure: This study was funded by HUTCHMED Limited. For full disclosures of the study authors, visit coi.asco.org.
