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 (OGSG1902).

366 Background: Large type 3 (≥8 cm) and type 4 gastric cancers are associated with extremely poor prognoses. Neoadjuvant chemotherapy (NAC) has been proposed as a potential strategy to improve outcomes in these patients. The phase III JCOG0501 trial, which compared neoadjuvant S-1 plus cisplatin followed by D2 gastrectomy with upfront surgery, failed to demonstrate a survival benefit for the neoadjuvant approach. Based on the results of the PRODIGY study, DOS therapy was considered a potential candidate for large type 3 or type 4 gastric cancer. Methods: Patients with large type 3 or type 4 gastric cancer without distant metastases, except for positive peritoneal cytology (CY), were eligible. Staging laparoscopy was mandatory. Participants received three cycles of neoadjuvant DOS therapy (docetaxel 40 mg/m² and oxaliplatin 100 mg/m² intravenously on day 1, and oral S-1 at 80 mg/m² for 14 days, repeated every 3 weeks), followed by gastrectomy with ≥D2 lymphadenectomy. Patients who achieved R0 resection subsequently received adjuvant docetaxel plus S-1 therapy for one year. 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-sided log-rank test was used with α=0.10 and power (1−β) =0.8. Results: Between October 2019 and February 2022, 48 patients were enrolled. The median age was 66 years (range: 44–79), and 29 patients (60.4%) were male. Twenty-seven patients (56.2%) had type 4 tumors. Positive CY was observed in 10 patients (20.8%). Clinical stage III and IV disease were observed in 24 (50.0%) and 11 (22.9%) patients, respectively. NAC was completed in 91.7% of patients. The 3-year PFS rate was 37.5% (95% confidence interval CI: 24.1–50.6%, 80% CI: 28.6–46.4%, p = 0.96), and the 3-year overall survival (OS) rate was 52.1% (95% CI: 37.2–65.0%). Among 10 patients with measurable lesions, the objective response rate was 50.0%. The R0 resection rate was 89.6%. A pathological response of grade 1b or higher was achieved in 66.7% of patients. CY conversion to negative was achieved in 80.0% of cases. Grade 3 or 4 adverse events during NAC, including neutropenia and appetite loss, occurred in 37.5% of patients. Conclusions: This study demonstrated a favorable pathological response and acceptable safety profile of neoadjuvant DOS therapy for large type 3 or type 4 gastric cancer. However, the 3-year PFS did not exceed the null hypothesis threshold, and the survival benefit of DOS therapy could not be demonstrated. Clinical trial information: CRB5180012 .