Olaparib plus paclitaxel is active in the treatment of patients with metastatic gastric cancer, with a greater overall survival benefit in patients with low levels of ataxia telangiectasia mutated (ATM), a new study published online ahead of print in the Journal of Clinical Oncology has shown.1
Because gastric cancer cell lines, particularly those with low levels of ATM, are sensitive to olaparib, a poly (ADP-ribose) polymerase inhibitor, researchers sought to evaluate the efficacy of olaparib plus paclitaxel compared with paclitaxel alone in patients with recurrent or metastatic gastric cancer and assess whether low ATM, a key activator of DNA damage, expression is associated with improved outcomes.
For the double-blind, phase 2 study, researchers enrolled 123 patients and randomly assigned them to receive olaparib 100 mg orally twice daily plus paclitaxel 80 mg/m2 IV on days 1, 8, and 15 of each 28-day cycle or placebo plus paclitaxel. Patients then received maintenance monotherapy with olaparib 200 mg twice daily or placebo.
Results showed no significant difference in progression-free survival between the two treatment arms; however, olaparib plus paclitaxel significantly improved overall survival compared with paclitaxel plus placebo in both the overall population (HR=0.56; 80% CI: 0.41-0.75; P=0.005) and among those with low ATM expression (HR=0.35; 80% CI: 0.22-0.56; P=0.002).
In regard to safety, olaparib plus paclitaxel was generally well tolerated among patients who received the combination. No unexpected safety findings were observed.
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A phase 3 trial is currently evaluating this regimen is currently underway.
Olaparib is already indicated for the treatment of patients with germline BRCA mutated advanced ovarian cancer who have received 3 or more prior lines of chemotherapy.
- Bang Y-J, Im S-A, Lee K-W, et al. Randomized, double-blind phase II trial of prospective classification by ATM protein level to evaluate the efficacy and tolerability of olaparib plus paclitaxel in patients with recurrent or metastatic gastric cancer [published online ahead of print August 17, 2015]. J Clin Oncol. doi: 10.1200/JCO.2014.60.0320.