In the Asian phase III GOLD trial reported in The Lancet Oncology, Bang et al found that the addition of olaparib (Lynparza) to paclitaxel did not significantly improve overall survival among patients with previously treated advanced gastric cancer, including those with ataxia-telangiectasia–mutated protein (ATM)-negative tumors.
In the double-blind trial, 525 patients from 58 sites in China, Japan, South Korea, and Taiwan were randomized between September 2013 and March 2016 to receive oral olaparib at 100 mg twice daily plus intravenous paclitaxel at 80 mg/m2 (n = 263) or matching placebo plus paclitaxel (n = 262). In total, 94 patients were determined to have ATM-negative tumors before unmasking for the primary analysis, consisting of 48 in the olaparib plus paclitaxel group and 46 in the control group.
The primary endpoints were overall survival among all patients and among those with ATM-negative tumors. A significant difference was defined as P < .025. The trial is ongoing but no longer recruiting patients.
The median duration of follow-up for overall survival was 11.1 months in the olaparib group vs 9.9 months in the control group among all patients and 12.6 vs 15.4 months among ATM-negative patients. The median overall survival was 8.8 months in the olaparib group vs6.9 months in the control group among all patients (hazard ratio [HR] = 0.79, P = .026) and 12 months vs 10 months among ATM-negative patients (HR = 0.73, P = .25).
Among all patients, the most common grade ≥ 3 adverse events in the olaparib group were neutropenia (30% vs 23% in control group), leukopenia (16% vs 10%), and decreased neutrophil count (15% vs 7%). Serious adverse events occurred in 35% vs 25%. Death considered related to treatment occurred in one patient in the olaparib group (liver injury) and one patient in the control group (cardiac failure).
The investigators concluded: “The GOLD study did not meet its primary objective of showing a significant improvement in overall survival with olaparib in the overall or ATM-negative population of Asian patients with advanced gastric cancer. The study generated informative efficacy and safety data regarding the use of olaparib in combination with a chemotherapeutic agent and provides a foundation for future studies in this difficult-to-treat patient population.”
The study was funded by AstraZeneca.
Yung-Jue Bang, MD, of Seoul National University College of Medicine, is the corresponding author of The Lancet Oncology article.
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