Phase III trial comparing XELOX regimen (oxaliplatin plus capecitabine) versus EOX regimen (epirubicin, oxaliplatin and capecitabine) as first-line treatment for advanced gastric cancer: EXELOX trial.
Authors: Weijian Guo, Xiaodong Zhu, Mingzhu Huang, Yusheng Wang, Zhiyu Chen, Wanjing Feng, Yifu He, Xiaowei Zhang, Xin Liu, Chenchen Wang, Wen Zhang, Jieer Ying, Jun Wu, Lei Yang, Yanru Qin, Xiaoying Zhao, Wenhua Li, Zhe Zhang, Lixin Qiu, XiaoFeng Wang
Journal: Journal of Clinical Oncology (2021)

4014 Background: At present, there is no standard chemotherapy regimen for advanced gastric cancer (AGC), and there is no consensus whether the three-drug combination is better than two-drug combination in first-line treatment. Both of XELOX regimen and EOX regimen are widely recommended as firs-line chemotherapy regimens for AGC. In this EXELOX trial, we aimed to compare the efficacy and safety of EOX and XELOX regimens. Methods: EXELOX is an open-label, multicenter, prospective, randomized phase III trial that enrolled 448 previously untreated patients with histologically confirmed advanced gastric adenocarcinoma from 7 hospitals in China. Patients were randomly assigned (1:1) to receive XELOX regimen (oxaliplatin 130mg/m 2 d1; xeloda 1000mg/m 2 bid d1-14) or EOX regimen (epirubicin 50mg/m 2 d1; oxaliplatin 130mg/m 2 d1; xeloda 1000mg/m 2 bid d1-14) in this study. Treatment was repeated every 3 weeks until disease progression, intolerable toxicity, patient death, withdrawal of informed consent, or up to eight cycles, followed by xeloda single-agent maintenance. We stratified randomization by Eastern Cooperative Oncology Group status, extent of disease(locally advanced/metastatic) and clinical trial center. Patients and clinicians were not masked to the allocated treatment. The primary endpoint was progression-free survival (PFS) on an intention-to-treat basis with a non-inferiority upper margin of 1.3 for the hazard ratio (HR). The clinical trial was a non-inferiority study that was registered with ClinicalTrials.gov, Number NCT02395640. The study is ongoing, but no longer recruit new participants. Results: Between Apr 10,2015 and Aug 20,2020, a total of 448 AGC patients were randomized to receive XELOX (n = 222) or EOX (n = 226). In ITT basis, the median PFS was 5.0 months (95%CI 4.5-6.0) in XELOX group and 5.5 months (95%CI 5.0-6.0) in EOX group (HR 0.989, 95%CI 0.812-1.203; P non-inferiority = 0.0032). In Per-protocol population (n = 428), the median PFS was 5.0 months (95%CI 5.0-6.0) in XELOX group and 5.5 months (95%CI 5.0-6.0) in EOX group (HR 0.983, 95%CI 0.807-1.198; P non-inferiority = 0.0028). The incidence of grade 3-4 adverse events (AEs) was 42.2% (90/213) in XELOX group and 72.5(156/215) in EOX group ( p= 0.001). The most common grade 3-4 AEs were neutropenia (affecting 13.1% (28/213) in XELOX group and 48.4%(104/215) in EOX group ( p= 0.000). The incidence of chemotherapy dose reduction was 35% (75/213) in XELOX group and 55% (120/215) in EOX group( p= 0.009). One treatment-related death (lung infection) was observed in EOX group, and none in XELOX group. Conclusions: XELOX regimen is noninferior to EOX regimen in PFS with a better safety profile as first-line treatment for AGC patients, therefore XELOX is a more favorable choice and might be one of the standard first-line chemotherapy regimens. Clinical trial information: NCT02395640.