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Key Trials Show Utility of Agents Across Therapeutic Classes in Gastric/GEJ Cancer

Caroline Seymour
Published: Friday, Mar 15, 2019

Hope E. Uronis, MD, MHS

Hope E. Uronis, MD, MHS

Although there has been an increase in the incidence of esophageal and gastroesophageal junction (GEJ) adenocarcinoma, physicians have seen an improvement in overall survival (OS) over the last 40 years, due to strides made with VEGF inhibitors, TAS-102 (trifluridine/tipiracil; Lonsurf), and checkpoint inhibition.

During her lecture, Uronis shed light on these therapeutic classes and the trials that have demonstrated their utility and refined their applicability across settings, subpopulations, and histologies of gastric/GEJ cancer.

VEGF Inhibition

Bevacizumab (Avastin) was the first VEGF inhibitor to be tested in combination with chemotherapy as frontline therapy in patients with advanced gastric cancer in the phase III AVAGAST trial. However, the combination of bevacizumab, fluoropyrimidine, and cisplatin failed to demonstrate a statistically significant benefit in OS over placebo, said Uronis.

“The bottom line is, there are no candidate biomarkers identified, although there is an ongoing analysis with the ramucirumab studies,” explained Uronis. “Those remain to be seen.”


In the refractory setting, patients with ≥2 prior lines of therapy and an ECOG performance status of 0 or 1 were randomized 2:1 to receive either 35 mg/m2 of twice daily TAS-102 on days 1 to 5 and 8 to 12 of every 28-day cycle or placebo in the phase III TAGS trial.5 Patients were stratified by prior gastrectomy, representing approximately 44% of patients in both arms, said Uronis. Patients were further stratified by ECOG performance status, region of the world, and prior exposure to ramucirumab. Gastric cancer represented the predominant primary site, at 71% in both arms, said Uronis.
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