AstraZeneca has announced that Lynparza (olaparib) in combination with paclitaxel chemotherapy, compared with paclitaxel chemotherapy alone, did not meet the primary endpoint of overall survival (OS) in the Phase III GOLD trial in advanced gastric cancer patients, in either the overall population or patients whose tumor tested negative for Ataxia-Telangectasia Mutated (ATM) protein. Whilst there was a numerical survival trend in the Lynparza plus paclitaxel arm, it did not meet statistical significance.
Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: “While there was a numerical trend for survival benefit with Lynparza plus paclitaxel in the GOLD trial, we are disappointed that this did not reach statistical significance. The particular regimen in the GOLD study, at a low dose and in combination with chemotherapy, differs from other Phase III trials in the Lynparza programme. We look forward to presenting the GOLD data and remain confident in Lynparza’s clinical activity in a range of tumor types, including its approved use in BRCA-mutated ovarian cancer.”
GOLD was a randomized, double-blinded, placebo-controlled, multicenter Phase III trial to assess the efficacy and safety of Lynparza in combination with paclitaxel, compared with paclitaxel alone. The trial enrolled Asian patients with advanced HER2-negative gastric cancer (including the gastro-oesophageal junction) who had progressed following 1st-line therapy. The trial, conducted in China, Japan, South Korea and Taiwan where gastric cancer is particularly prevalent, enrolled a total of 525 patients - 18% of whom had tumours that tested ATM negative by immunohistochemistry (IHC). Lynparza was given orally at a dose of 100mg twice daily in combination with paclitaxel IV infusion over 1 hour at 80mg/m2 weekly on days 1, 8 and 15 of a 28 day schedule.
The reported incidence of adverse events for Lynparza in combination with paclitaxel compared with paclitaxel alone was similar.
A full evaluation of the data is ongoing and the results will be submitted for presentation at an upcoming medical meeting.
Lynparza is approved in over 40 countries for use as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed BRCA-mutated (germline and/or somatic) high grade serous epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy. It is approved in the US as monotherapy in patients with deleterious or suspected deleterious germline BRCA-mutated advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy.