Addition of Docetaxel to Oral Fluoropyrimidine Improves Efficacy in Patients With Stage III Gastric Cancer: Interim Analysis of JACCRO GC-07, a Randomized Controlled Trial

Abstract

PURPOSE S-1 is a standard postoperative adjuvant chemotherapy for patients with stage II or III gastric cancer in Asia. Neoadjuvant or perioperative strategies dominate in Western countries, and docetaxel has recently shown significant survival benefits when combined with other standard regimens in advanced cancer and perioperative settings. PATIENTS AND METHODS This randomized phase III study was designed to prove the superiority of postoperative S-1 plus docetaxel over S-1 alone for R0 resection of pathologic stage III gastric cancer. The sample size of 1,100 patients was necessary to detect a 7% increase in 3-year relapse-free survival as the primary end point (hazard ratio, 0.78; 2-sided α = .05; β = .2). RESULTS The second interim analysis was conducted when the number of events reached 216 among 915 enrolled patients (median follow-up, 12.5 months). Analysis demonstrated the superiority of S-1 plus docetaxel (66%) to S-1 (50%) for 3-year relapse-free survival (hazard ratio, 0.632; 99.99% CI, 0.400 to 0.998; stratified log-rank test, P < .001), and enrollment was terminated as recommended by the independent data and safety monitoring committee. Incidences of grade 3 or greater adverse events, particularly neutropenia and leukopenia, were higher in the S-1 plus docetaxel group, but all events were manageable. CONCLUSION Addition of docetaxel to S-1 is effective with few safety concerns in patients with stage III gastric cancer. The present findings may also be applicable in countries in which perioperative adjuvant chemotherapy or chemoradiation is not standard.

The Methods of Lymph Node Examination Make a Difference to Node Staging and Detection of N3b Node Status for Gastric Cancer

“…However, subgroup analysis found that the 5-year OS rate of stage IIIB GC patients was 50.2% in the group receiving S-1 after surgery and 44.1% in the group receiving surgery only (HR, 0.791; 95% CI, 0.520-1.205), indicating that there is still some room for improvement. Recently, the Japan Clinical Cancer Research Organization (JACCRO) further conducted the JACCRO GC-07 trial, showing that S-1 plus docetaxel for 6 months and followed by S-1 alone for 6 months is a better choice for stage III GC patients (31,32). In Western patients, postoperative chemoradiotherapy should be a considered addition for these patients (33).…”

Indication and Prognostic Significance of Conversion Surgery in Patients with Liver Metastasis from Gastric Cancer

“…Gastric cancer is a common gastrointestinal malignant neoplasm and is the third leading cause of cancer-related mortality worldwide [1]. The survival outcomes of patients with resectable gastric cancer have been gradually improved via standard gastrectomy with D2 lymphade-DOI: 10.1159/000505555 nectomy, neoadjuvant chemotherapy, and adjuvant chemotherapy [2][3][4]. However, patients with stage IV gastric cancer including liver metastasis still have a poor prognosis.…”

Perioperative chemotherapy for locally advanced gastric cancer in Japan: current and future perspectives

“…The ACTS-GC trial demonstrated the efficacy of postoperative adjuvant chemotherapy with S-1 for patients with pStage II/III gastric cancer, but found unsatisfactory 5-year survival rates for those with pStage IIIA and IIIB, of 67.1% and 50.2%, respectively, according to the thirteenth edition of the Japanese classification of gastric carcinoma, highlighting the need for improvement [5,6]. Accordingly, the efficacy of intensified postoperative adjuvant chemotherapy with a doublet regimen was investigated and the JACCRO GC-07 confirmed the superiority of S-1 plus docetaxel over S-1 monotherapy [28]. Consequently, postoperative adjuvant chemotherapy with doublet regimens became standard treatments for pStage III gastric cancer.…”

“…JACCRO (Japan Clinical Cancer Research Organization) GC-07 was a randomized controlled trial that evaluated the superiority of postoperative S-1 plus docetaxel (DS) over S-1 monotherapy in patients with pStage III gastric cancer. The study was terminated at the second interim analysis, because far better RFS of the S-1 plus docetaxel group was demonstrated (HR, 0.632; 99.99% CI, 0.400-0.998) with 3-year RFS rates of 66% in the S-1 plus docetaxel group and 50% in the S-1 monotherapy group [28].…”