Subgroup analysis of JCOG0501 phase III study to confirm superiority of additional neoadjuvant chemotherapy with S-1 plus cisplatin to D2 gastrectomy with S-1 adjuvant chemotherapy for resectable type IV or large type III gastric cancer.
110 Background: We previously reported that the superiority of neoadjuvant chemotherapy (NAC) with S-1 plus cisplatin was not demonstrated for schirrhous or similar macroscopic type (type 4 or large type 3) gastric cancer. However, overall survival (OS) in both arms was better than previous reports (3-year OS: 62.4% in gastrectomy plus adjuvant S-1 [arm A] and 60.9% in NAC followed by gastrectomy plus adjuvant S-1 [arm B]). Therefore, we explored whether histology and peritoneal cytology are associated with treatment effect. Methods: After staging laparoscopy, a total of 300 eligible patients with clinically resectable disease were randomized to arm A, or arm B. In this report, treatment effect was explored in key subgroups such as histology and peritoneal cytology using the data from JCOG0501. Cox regression model was used to investigate the interaction between arms and subgroups. Results: Hazard ratio (HR) classified by histology (excluding one missing) was 0.686 (95% CI: 0.414-1.138) for non-signet type (n = 123) and 1.158 (95% CI: 0.805-1.666) for signet type (n = 176) (p = 0.098 for interaction). HR by peritoneal cytology was 0.870 (95%CI: 0.616-1.228) for the negative (n = 240) and 1.051 (95% CI: 0.598-1.845) for the positive (n = 60) (p = 0.513 for interaction). 3 year-OS of signet ring cell histology was 63.2% (95% CI: 52.2-72.4) in arm A and 51.7% (95% CI: 40.9-61.5) in arm B, that of non-signet ring cell histology was 62.3% (95% CI: 48.9-73.1) in arm A and 74.2% (95% CI: 61.4-83.3) in arm B, and that of peritoneal cytology positive was 35.7% (95% CI: 18.9-53.0) in arm A and 25.0% in arm B (95% CI: 11.8-40.7), and that of peritoneal cytology negative was 68.6% (95% CI: 59.5-76.1) in arm A and 70.6% (95% CI: 61.5-77.9) in arm B. Conclusions: NAC might be beneficial for non-signet ring cell histology. Considering the survival results, primary surgery followed by S-1 could be recommended for this disease even though histology was signet ring cell type or peritoneal cytology was positive. Clinical trial information: UMIN000000279.