A multicenter, randomized phase III trial comparing second-line chemotherapy (SLC) plus best supportive care (BSC) with BSC alone for pretreated advanced gastric cancer (AGC).

Abstract

4004 Background: Currently no evidence that SLC in AGC patients will result in substantial prolongation of survival when compared to BSC exists, and there is potential for toxicity from the treatment. The efficacy and safety of SLC using either single-agent docetaxel or irinotecan was evaluated in a randomized phase III trial. Methods: Two-hundreds two patients with AGC, one or two prior chemotherapy regimen(s) involving both fluoropyrimidines and platinum, and an Eastern Cooperative Oncology Group performance status (PS) 0 or 1 were randomly assigned 2:1 to SLC or BSC. Choice of SLC, either docetaxel 60 mg/m2 every 3 weeks or irinotecan 150 mg/m2 every 2 weeks, was left to the discretion of investigators. Randomization was stratified by PS and the number of prior chemotherapy. All patients received standard BSC regimen a priori defined in the study protocol. Primary endpoint was the overall survival (OS). Results: Between Sep 2008 and Sep 2010, 193 eligible patients, 74% with one prior chemotherapy and 54% with PS 0, were enrolled: SLC (n=128) or BSC (n=65). SLC was generally well tolerated, with all-cause deaths within 30 days of random assignment of 3% and 4%, respectively, on SLC and BSC arm. As of current analysis, 128 (66%) patients died. In the intent-to-treat population, a significant difference in OS (5.1 months for SLC v 3.8 months for BSC) was observed (hazard ratio, 0.63; 95% confidence interval, 0.47-0.86; P=0.004). The OS benefit for SLC was relevant in most of the prospectively defined subgroups including age, gender, PS, number of prior treatments, number of metastatic sites, hemoglobin levels, and response to prior chemotherapy. Significantly more patients on SLC arm received further salvage chemotherapy than those on BSC arm (40% v 22%, respectively; P=0.011). Conclusions: This is the largest phase III trial comparing SLC plus BSC with BSC alone in AGC. In pretreated patients, SLC is tolerated and significantly improves OS when added to BSC.