Results from a phase 3 trial, published in Gastric Cancer, found that the addition of docetaxel to S-1 as postoperative chemotherapy was associated with superior 5-year survival outcomes compared with S-1 alone in patients with stage III gastric cancer following gastrectomy. These findings provide an update to previously reported results of the JACCRO GC-07 study, which evaluated 3-year relapse-free survival (RFS) with docetaxel plus S-1.
JACCRO GC-07 was a randomized, phase 3 trial comparing S-1 plus docetaxel versus S-1 monotherapy in a postoperative adjuvant setting for patients with stage III gastric cancer following D2 gastrectomy. In total, 912 patients were included. Interim analysis and a secondary follow-up analysis were reported in the Journal of Clinical Oncology in 2019 and in Gastric Cancer in 2022, respectively. In the trial, the control group was randomized to 12 months of S-1 monotherapy. The test arm was assigned to a triweekly combination regimen of oral S-1 with intravenous docetaxel (40 mg/m2) on day 1. Six cycles of the combination therapy were to be administered after 1 cycle of S-1 monotherapy, followed by further monotherapy for 12 months. The protocol was initiated within 42 days postoperatively.
The current study reported 5-year follow-up results regarding the secondary end point of 5-year overall survival (OS), RFS, and adverse events. Recurrence was reported in 190 patients in the treatment arm and 236 patients in the control arm. Regarding deaths, 167 patients and 206 patients died in the treatment and control arms, respectively.
The 5-year OS rate was 67.91% in the S-1 plus docetaxel group compared with 60.27% in the monotherapy arm (hazard ratio [HR], 0.752; 95% CI, 0.613-0.922; P=.0059). For patients with stage IIIA disease, 5-year OS rates were 81.80% and 72.21% in the treatment and control arms, respectively (HR, 0.573; 95% CI, 0.357-0.921; P=.0198); for those with stage IIIC disease, 5-year OS was 56.14% and 41.81%, respectively (HR, 0.706; 95% CI, 0.520-0.958; P=.0246). The authors noted no significant improvement in OS with the docetaxel combination for patients with stage IIIB disease (66.14% vs 66.42%, respectively; HR, 0.915; 95% CI, 0.652-1.284; P=.6058).
Five-year RFS rates were 59.78% with S-1 plus docetaxel compared with 50.63% for S-1 monotherapy (HR, 0.726; 95% CI, 0.599-0.879; P=.0010). HRs for 5-year RFS with the combination treatment for patients with stage IIIA, IIIB, and IIIC disease were 0.600 (P=.0140), 0.871 (P=.4035), and 0.675 (P=.0073), respectively. Rates of late recurrence (diagnosed after 3 years from randomization) were similar between treatment arms, and the most common site of late recurrence was the peritoneal surface.
“Recurrences through lymphatic and hematogenous routes, along with the total number of recurrences, remained significantly suppressed by the addition of docetaxel during the 5 years of follow-up,” the authors noted.
Rates of death from other cancer or disease over the course of follow-up were not different between groups. Data on adverse events were similar to the previously reported findings from this trial.
“The evidence recommending postoperative chemotherapy with S-1 and docetaxel is robust for patients with pathologically stage III gastric cancer who undergo D2 resection, regardless of the histological type,” the authors concluded, “although late recurrences at >3 years after randomization remain unpreventable.”
