The addition of radiotherapy to the S-1 plus oxaliplatin (SOX) chemotherapy regimen did not improve disease-free or overall survival in patients with pathologic T4 and/or node-positive gastric adenocarcinoma who underwent D2 gastrectomy (ie, R0 resection with D2 lymphadenectomy), based on a phase III trial published by Wang et al in JAMA Network Open.
“The primary findings therefore support chemotherapy alone after D2 gastrectomy as an appropriate adjuvant approach for most patients with T4 [and/or] node-positive gastric cancer,” the investigators wrote.
Study Details
The open-label trial focused on 620 patients aged 18 to 70 years with T4 (44.2%) and/or node-positive (95.2%) disease and no evidence of metastasis who underwent D2 gastrectomy at five tertiary hospitals in China. They were randomly assigned in a 1:1 ratio to receive adjuvant SOX with radiotherapy (n = 309) or SOX alone (n = 311).
Patients assigned to the experimental arm received one induction cycle of SOX, followed by radiotherapy to 50.4 Gy in 28 fractions with concurrent S-1, and then three additional cycles of SOX. Those assigned to the control arm received six cycles of SOX every 3 weeks.
The primary endpoint was 3-year disease-free survival, with overall survival and adverse events assessed as secondary endpoints.
Key Findings
At the prespecified primary analysis, disease-free survival did not appear to differ between the arms (hazard ratio [HR] = 0.98, 95% confidence interval [CI] = 0.73–1.33). Kaplan-Meier estimates showed 3-year disease-free survival rates of 70.5% with SOX plus radiotherapy and 69.3% with SOX alone (log-rank P = .93).
Overall survival was also not found to differ between groups (HR = 0.86, 95% CI = 0.60–1.23). Estimated 3-year overall survival rates were 80.8% with SOX plus radiotherapy and 78.4% with SOX alone (log-rank P = .41).
Longer-term follow-up likewise showed no evidence of benefit from adding radiotherapy. At 5 years, disease-free survival rates were 60.0% with SOX plus radiotherapy and 57.3% with SOX alone (log-rank P = .76), and overall survival rates were 73.7% and 71.4%, respectively (log-rank P = .55).
Overall, subgroup analyses for disease-free survival did not appear to indicate differences in treatment effect across baseline subgroups. For overall survival, patients with T4a disease had a HR of 0.65 (95% CI = 0.43–0.98), although the interaction test did not demonstrate heterogeneity of treatment effect by T stage (P for interaction = .11).
Treatment-related adverse events were reported to be similar between the arms.
“These findings suggest that routine intensification with postoperative radiotherapy added to adjuvant SOX may not be warranted after D2 R0 resection for T4 [and/or] node-positive gastric cancer,” the investigators concluded. “Any apparent overall survival difference in the T4a subgroup should be interpreted cautiously as hypothesis-generating and confirmed in future studies.”
Feng Bi, MD, of Sichuan University, China, is the corresponding author of the JAMA Network Open article.
Disclosure: The study was funded by the Project for Artificial Intelligence, West China Hospital of Sichuan University; National Natural Science Foundation of China; and Support Project 2024YFFK0338, Sichuan Science and Technology. The study authors reported no conflicts of interest.
