An interim analysis of data from a phase 3 clinical trial showed significantly improved relapse-free survival (RFS) for patients with resected stage III gastric cancer receiving postoperative chemotherapy with the combination of S-1 and docetaxel compared with those receiving S-1 alone, and resulted in early termination of the study. The findings from this study were published in the Journal of Clinical Oncology.
Clinical trials conducted in Asia that have evaluated use of chemotherapy in the treatment of patients with resectable gastric cancer have historically focused on the postoperative setting, as opposed to preoperative chemotherapy or preoperative chemoradiation therapy.
For example, previous studies of these patients involving surgery followed by postoperative adjuvant chemotherapy with either S-1 or capecitabine-oxaliplatin doublet demonstrated improved overall survival (OS) compared with surgery alone.2,3
In this open-label, randomized, controlled phase 3 study evaluating the combination of S-1 with docetaxel in Asian patients with R0-resected, stage III gastric cancer, 915 patients were randomly assigned in a 1:1 ratio to S-1 plus docetaxel or S-1 alone. The 2 study arms were stratified according to gender, age, Eastern Cooperative Oncology Group (ECOG) performance status, as well as disease characteristics, including tumor stage, histology, nodal status, and surgical procedure performed. The primary end point of the study was 3-year RFS; secondary end points included 5-year RFS, 3- and 5-year overall survival (OS), and safety.
A key finding observed at interim analysis was significantly improved RFS for patients receiving combination chemotherapy compared with S-1 alone. Three-year RFS rates were 66% and 50% for patients assigned to combination therapy vs S-1 alone, respectively (hazard ratio [HR]=0.632; 99.99% CI, 0.400-0.998; stratified log-rank test, P <.001).
As of April 2017 (the time of this interim analysis), there were only 44 and 60 deaths in the docetaxel plus S-1 and S-1 alone arms, respectively, with no significant difference in OS (P =.13).
The dose of docetaxel was reduced for 28% of patients receiving this agent. With respect to adherence to oral S-1 for patients receiving combination therapy, 89%, 77%, 66%, and 49% of patients were on treatment at 3 months, 6 months, 9 months, and 12 months, respectively, following initiation of S-1. Similar adherence rates were observed for patients taking S-1 alone.
Grade 3 or higher adverse events occurred in 58% and 42% of patients receiving docetaxel plus S-1 and S-1 alone, respectively. In the docetaxel plus S-1 arm, the most common grade 3 adverse events were neutropenia, leukopenia, anorexia, febrile neutropenia, mucositis oral, anemia, and nausea. Hospitalization due to severe adverse events occurred in 14% of patients receiving docetaxel plus S-1 and 12% of patients receiving S-1 alone. One treatment-related grade 5 respiratory adverse event occurred in a patient receiving S-1 alone.
“In conclusion, the present results demonstrate a significant clinical benefit of adding docetaxel to S-1. Therefore, this combination can be recommended as a standard postoperative adjuvant chemotherapy for patients with stage III gastric cancer,” the study authors noted.
- Yoshida K, Kodera Y, Kochi M, et al. Addition of docetaxel to oral fluoropyrimidine improves efficacy in patients with stage III gastric cancer: Interim analysis of JACCRO GC-07, a randomized controlled trial [published online March 29, 2019]. J Clin Oncol. doi: 10.1200/JCO.18.01138
- Sasako M, Sakuramoto S, Katai H, et al. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol. 2011;29(33):4387-4393.
- Noh SH, Park SR, Yang HK, et al. Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): 5-year follow-up of an open-label, randomised phase 3 trial. Lancet Oncol. 2014;15(12):1389-1396.