Neoadjuvant docetaxel, oxaliplatin, and S-1 plus surgery followed by adjuvant docetaxel and S-1 for patients with large type 3 or type 4 gastric cancer: Short-term outcomes of the phase II OGSG1902 trial.

4031 Background: Patients with large type 3 (≥8 cm) or type 4 gastric cancer (GC) face a dismal prognosis, necessitating the development of multidisciplinary treatment, including neoadjuvant chemotherapy. We present the short-term results from the OGSG1902 (jRCTs051190060) trial, where resectable large type 3 or type 4 GC patients were treated with neoadjuvant docetaxel (DTX)/oxaliplatin (L-OHP)/S-1 (DOS) plus surgery and adjuvant DTX/S-1 (DS) therapy. Methods: Untreated large type 3 or type 4 GC patients without distant metastasis other than positive peritoneal lavage cytology (CY), aged 20-80 years, and with ECOG PS 0-1, were enrolled. Patients received three cycles of DTX (40 mg/m 2 , day1) + L-OHP (100 mg/m 2 , day1) + S-1 (80 mg/m 2 , day1-14) every 3 weeks, followed by gastrectomy with D2 lymph node dissection and 1-year DS therapy. The primary end point was the 3-year progression-free survival (PFS) rate. The secondary end points included PFS time, overall survival time, pathological response rate, response rate according to RECIST version 1.1, neoadjuvant chemotherapy completion rate, R0 resection rate, protocol completion rate, CY negative conversion rate, adverse event occurrence rate, and nutritional evaluation. Results: Forty-eight patients (pts) were enrolled from 2019 to 2022. The neoadjuvant chemotherapy completion rate was 91.7%, pathological response rate (≥Grade 1b) was 66.7%, response rate according to RECIST version1.1 for 10 pts with measurable lesions was 50.0%, CY negative conversion rate for nine CY positive pts was 88.9%, R0 resection rate was 89.6%, and the protocol completion rate was 45.8%. Adverse events (≥CTCAE Grade 3) during neoadjuvant DOS included neutropenia in 18 pts (38%), febrile neutropenia in one pt (2%), nausea in five pts (10%), diarrhea in six pts (13%), and anorexia in 18 pts (38%). Gastrectomy was performed in 47 pts total/distal gastrectomy: 32(68%)/15(32%). Major postoperative complication (≥Clavien-Dindo Grade IIIa) was observed in one pt (2%), including pleural infection. Adverse events (≥CTCAE Grade 3) in 39 patients receiving adjuvant DS therapy included neutropenia in 16 pts (41%), anemia in five pts (13%), nausea in one pt (3%), diarrhea in two pts (5%), anorexia in nine pts (23%), fatigue in three pts (8%), and febrile neutropenia in four pts (10%). No treatment-related deaths were observed. Conclusions: Neoadjuvant DOS therapy for large type 3 or type 4 GC demonstrates promising efficacy with high histological response and acceptable adverse events. Future analysis of survival outcomes is planned. Clinical trial information: jRCTs051190060 .