Neoadjuvant docetaxel, oxaliplatin, and S-1 therapy for patients with large type 3 or type 4 gastric cancer: final outcomes of a multicenter, phase II study (OGSG 1902).

[BACKGROUND] Large type 3 (≥ 8 cm) and type 4 gastric cancers are associated with extremely poor prognoses. The phase III JCOG0501 trial, which evaluated neoadjuvant S-1 plus cisplatin, failed to demonstrate any survival benefits. Docetaxel, oxaliplatin, and S-1 (DOS) have been explored as more effective perioperative regimens for these tumors.

[METHODS] Eligible patients had large type 3 or type 4 gastric cancer without distant metastases, except for positive peritoneal cytology (CY). Patients received three cycles of neoadjuvant DOS (docetaxel 40 mg/m, oxaliplatin 100 mg/m, and oral S-1 at 80 mg/m/day for 14 days), followed by gastrectomy with ≥ D2 lymphadenectomy and one year of adjuvant docetaxel plus S-1. The primary endpoint was the 3 year progression-free survival (PFS) rate, with an expected value of 60% and a threshold of 45%. A one-sample log-rank test was performed with an α level of 0.10.

[RESULTS] Of the 48 patients enrolled, 27 had type 4 tumors (56.2%), and 10 (20.8%) had CY1. Overall, 91.7% of patients completed neoadjuvant DOS. R0 resection rate was achieved in 89.6% of patients, a pathological response grade ≥ 1b in 66.7%, and negative CY conversion in 80.0%. The 3-year PFS rate was 37.5% (95% confidence interval [CI], 24.1-50.6%; 80% CI 28.6-46.4%; p = 0.960), and the 3-year overall survival rate was 52.1% (95% CI 37.2-65.0%).

[CONCLUSIONS] Although neoadjuvant DOS therapy demonstrated favorable pathological responses, the 3-year PFS did not exceed the predefined threshold, and a survival benefit was not demonstrated.