ASCO Expert Perspective
“In the FRUTIGA study, the combination of fruquintinib and paclitaxel fulfills the primary endpoint of progression-free survival versus paclitaxel in patients with advanced gastric or gastroesophageal junction adenocarcinoma. These findings suggest a new combination of fruquintinib and paclitaxel may be considered a potential option in the 2nd line setting.”
– Cathy Eng, MD, FACP, FASCO, ASCO Expert in gastrointestinal cancers

Results from a new phase 3 study conducted in China demonstrated a significant improvement in progression-free survival in patients with advanced stomach cancers. According to the authors, this is the first phase 3 trial to demonstrate survival benefits with a new treatment alternative to ramucirumab-containing therapy in the second-line setting for patients with advanced gastric or gastroesophageal junction adenocarcinoma. These results will be presented during the February 2024 session of the American Society of Clinical Oncology (ASCO) Plenary Series.

The FRUTIGA trial evaluated the efficacy and safety of fruquintinib plus paclitaxel versus 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 survival and overall survival.

Roughly 49.5% of patients with gastric or gastroesophageal junction adenocarcinoma receive second-line treatment based on available epidemiology data from 2021. Fruquintinib is already approved in the U.S. and China for third- and later-line treatments of patients with metastatic colorectal cancer.

Fruquintinib is an oral vascular endothelial growth factor (VEGF) receptor inhibitor of VEGFR 1, 2, and 3. VEGF controls the formation of new blood vessels and can be blocked with certain drugs, such as fruquintinib. 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.

There were 703 patients enrolled in the study, and 699 patients received at least 1 dose of a study drug. Patient demographics were well balanced in both arms of the study: patients in the fruquintinib group were a median age of 57 years, 70.9% male, and 99.7% Asian; patients in the placebo group were a median age of 59 years, 68.2% male, and 100% were Asian. There was, however, an imbalance of patients receiving subsequent antitumor therapies across the two groups – 52.7% in the fruquintinib plus paclitaxel group versus 72.2% in the placebo plus paclitaxel group.

Key Findings

• Patients in the fruquintinib group had significantly improved progression-free survival compared to patients in the placebo group (5.55 months vs. 2.73 months, respectively).
• The overall response rate was significantly higher in the fruquintinib group compared to the placebo group (42.5% vs. 22.4%, respectively).
• After a median follow-up period of 31.7 months, the median overall survival was 9.63 months in the fruquintinib and paclitaxel arm and 8.41 months in the placebo and paclitaxel arm, but was not statistically significant. Post-hoc analyses were performed to adjust for subsequent antitumor therapies, resulting in:
  • A nominal statistically significant improvement in overall survival in the fruquintinib plus paclitaxel group.
  • Among patients with lymph node metastases and non-diffuse gastric/gastroesophageal adenocarcinoma median progression-free survival was even more prolonged (6.08 months in fruquintinib group vs. 2.69 months in the placebo group) and overall survival also showed a nominal statistically significant improvement (9.56 months vs. 7.85 months).
  • The authors also plan to present the results of overall survival sensitivity analyses during the February session.

The most common treatment-emergent adverse events of Grade ≥3 were neutropenia (60.0% vs. 36.4%), leukopenia (42.9% vs. 23.5%), and anemia (11.7% vs. 10.6%).

“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. Fruquintinib plus paclitaxel could be a promising second-line treatment option for patients with advanced gastric/gastroesophageal adenocarcinoma that progressed on first-line chemotherapy,” said lead study author Rui-hua Xu, MD, PhD from Sun Yat-sen University Cancer Center in Guangzhou, China.

Abstract and presentation will be available here on February 6, 2024 at 3:00 PM (ET).

Link to Expert Disclosures

Link to Author Disclosures

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