PARP inhibitors are also being evaluated in combination with other agents for treating gastric cancer.
The combination of olaparib plus paclitaxel has been studied in advanced gastric cancer, and demonstrated promising efficacy and safety results in a double-blind phase II trial (Study 39; NCT01063517) versus paclitaxel plus placebo . However, the phase III trial (GOLD trial; NCT01924533) did not meet its primary endpoint of overall survival benefit . Median overall survival in the overall patient population was 8.8 months (95% CI 7.4–9.6) in the olaparib group vs 6.9 months (6.3–7.9) in the placebo group; HR 0.79 (97.5% CI 0.63–1.00); p=0.026. In the ATM-compromised population (as determined by immunohistochemistry), median overall survival was 12.0 months (7.8–18.1) vs 10.0 months (6.4–13.3) for olaparib vs placebo respectively; HR 0.73 (0.40–1.34); p=0.25 .
Combination therapies that do not include chemotherapy are also being studied. Preliminary results from the phase II basket study of olaparib and the anti-programmed cell death ligand-1 (PD-L1) agent durvalumab (MEDIOLA; NCT02734004) have demonstrated reasonable tolerability and some efficacy (ORR 10%) in patients with relapsed gastric cancer, and this combination warrants further investigation in this population . Olaparib has also been combined with the angiogenesis inhibitor ramucirumab (NCT03008278) in patients with advanced gastric cancer, with results due in 2020.
- Bang YJ, Im SA, Lee KW et al. Randomized, Double-Blind Phase II Trial With Prospective Classification by ATM Protein Level to Evaluate the Efficacy and Tolerability of Olaparib Plus Paclitaxel in Patients With Recurrent or Metastatic Gastric Cancer. J Clin Oncol 2015; 33: 3858-3865.
- Bang YJ, Xu RH, Chin K et al. Olaparib in combination with paclitaxel in patients with advanced gastric cancer who have progressed following first-line therapy (GOLD): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol 2017; 18: 1637-1651.
- Bang Y-J, Kaufman B, Geva R et al. An open-label, phase II basket study of olaparib and durvalumab (MEDIOLA): Results in patients with relapsed gastric cancer. Journal of Clinical Oncology 2019; 37: 140-140.