A higher dose treatment for a type of metastatic gastric adenocarcinoma showed equivalent efficacy and safety, according to research published in the Journal of Clinical Oncology (published online June 2017; doi:10.1200/JCO.2016.71.6852).
Chemotherapy plus trastuzumab maintenance is considered standard of care for first-line human epidermal growth factor 2 (HER2)-positive metastatic gastric or gastroesophageal junction adenocarcinoma. Research has shown that patients with the lowest trastuzumab serum trough concentration have shorter overall survival (OS) after standard of care treatment. Thus, higher dose trastuzumab plus chemotherapy may help increase serum trough concentration and subsequently improve survival for such patients.
Manish A Shah, MD, Meyer Cancer Center, New York-Presbyterian/Weill Cornell Medical Center (New York, NY), and colleagues conducted an open-label trial to compare standard of care trastuzumab plus chemotherapy with higher-dose trastuzumab plus chemotherapy in first-line HER2-positive metastatic gastric or gastroesophageal junction adenocarcinoma. A total of 248 patients with no prior gastrectomy at least two metastatic sites were randomized to receive trastuzumab (8 mg/kg) followed by trastuzumab maintenance (6 mg/kg every 3 weeks; n = 124) or high-dose maintenance (10 mg/kg every 3 weeks; n = 124) combined with cisplatin (0 mg/m2 every 3 weeks) and capecitabine (800 mg/m2 twice per day in cycles 1-6). Baseline samples were recorded to measure trastuzumab serum trough concentrations.
Primary endpoint was OS in all randomized patients.
Researchers reported that the OS futility boundary was crossed and the study was stopped. Trough serum trastuzumab concentrations were increased in the high-dose group after the first maintenance dose and after six cycles, but this finding did not correlate with improved OS. Median OS was 10.6 months in the high-dose cohort and 12.5 months in the standard-dose cohort.
Safety data were comparable in the two cohorts. Common adverse events included nausea, vomiting, neutropenia, and anemia. Adverse events led to discontinuation of any study drug in 15% of patients in the high-dose cohort and 7% of patients in the standard-dose cohort.
Researchers concluded that, ““[High-dose] trastuzumab maintenance dosing was associated with higher trastuzumab concentrations, no increased efficacy, and no new safety signals.” These findings will not alter the standard of care for patients with metastatic gastric or gastroesophageal junction adenocarcinoma.—Zachary Bessette