Adjuvant S-1 plus docetaxel superior to S-1 monotherapy after a curative resection of stage III gastric cancer
In Asia, postoperative adjuvant chemotherapy with S-1 is a standard of care for curatively resected stage II/III gastric cancer. JACCRO GC-07 is a randomised controlled trial evaluating postoperative S-1 plus docetaxel compared to S-1 monotherapy in patients with stage III gastric cancer, following a D2 gastrectomy. Previous interim analyses have demonstrated a significant improvement in relapse-free survival (RFS) in patients who received S-1 plus docetaxel, compared to S-1 monotherapy. At ASCO GI 2021, an updated 3-year analysis of this study was presented confirming the superiority of the combination therapy.
S-1/docetaxel achieved a 3-year relapse-free survival of 67%
In the study at hand, a total of 912 eligible patients (gastrc cancer IIIA-IIIC, R0 resection, D2 lymph node dissection) were randomised to receive docetaxel 40mg/m2 on day 1 and S-1 80-120mg/body on days 1-14 every 21 days for 6 cycles followed by S-1 80-120mg/body on days 1-28 every 42 days for 4 cycles, or S-1 monotherapy 80-120mg/body on days 1-28 every 42 days for 8 cycles after a D2 gastrectomy. The primary endpoint was 3-year relapse-free survival, with overall survival (OS), tumour treating fields (TTF) and safety as key secondary study objectives.
At a median follow-up of 42.5 months, a total of 400 recurrences and 324 deaths had occurred. The RFS of patients who received S-1/docetaxel continued to be superior to what was observed in patients who received S-1 monotherapy, with a 3-year RFS rate of 67.7% and 57.4%, respectively (HR[95%CI]: 0.715[0.587-0.871], p= 0.0008). Similar results were observed in terms of OS, with a 3-year OS rate of 77.7% and 71.2%, for the S1-docetaxel combination and S1 monotherapy, respectively (HR[95%CI]: 0.742[0.596-0.925], P= 0.0076). The RFS obtained from adding docetaxel to A1 was particularly pronounced in patients with a stage IIIC tumour. In this subgroup, the 3-year RS rate reached 55.85% with S1/docetaxel as compared to only 39.25% for patients treated with adjuvant S1 alone (stage IIIA: 81.46% vs. 71.25%; stage IIIB: 66.14% vs. 61.61%). The time to treatment failure was similar in both treatment arms (p= 0.86). No significant interactions were observed between the treatment effect and specific clinical findings, such as age, gender, pStage, histologic type and tumour location,
These updated results support the findings of the previous interim analysis, with the adjuvant S-1/docetaxel combination being more efficacious that S-1 monotherapy in pStage III gastric cancer patients who have undergone a D2 gastrectomy without neoadjuvant chemotherapy.
Yoshida K et al., confirmed three-year RFS and OS of the randomized trial of adjuvant S-1 versus S-1 plus docetaxel after curative resection of pStage III gastric cancer (JACCRO GC-07). Presented at ASCO GI 2021; Abstract 159.