Multicenter phase 3 trial of adding intraperitoneal paclitaxel to first-line intravenous placlitaxel plus S-1 for gastric cancer with peritoneal metastasis

Gastric cancer with peritoneal metastasis has a poor prognosis, and survival with commonly used regimens, such as intravenous paclitaxel plus oral S-1, remains limited. The phase 3, parallel-group superiority DRAGON-01 trial, at 9 centers in China, evaluated addition of intraperitoneal paclitaxel to intravenous paclitaxel plus S-1. Adult patients with gastric adenocarcinoma and laparoscopically confirmed peritoneal metastasis without other metastases or prior systemic therapy were randomized 2:1 to 3-week cycles of intraperitoneal paclitaxel plus intravenous paclitaxel plus oral S-1 (IP group; n=148) or intravenous paclitaxel plus oral S-1 (PS group; n=74). Primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS) and safety. The median number of treatment cycles was 12 (IQR 8-20) in the IP group and 8 (4-15) in the PS group. This figure shows survival results. Median OS was 19.4 months in the IP group versus 13.9 months in the PS group (HR 0.67; 95% CI 0.50-0.90), with median PFS 11.2 months versus 7.2 months, respectively (HR 0.72; 95% CI 0.54-0.96). Grade 3 or 4 adverse events occurred in 38.5% of patients in the IP group and 41.9% of patients in the PS group; no treatment-related deaths occurred. The authors conclude that addint intraperitoneal paclitaxel to first-line intravenous paclitaxel plus oral S-1 significantly improved OS without increasing severe toxic effects (visual abstract).