Early endpoints of a randomized phase II trial of preoperative chemotherapy with S-1/CDDP with or without trastuzumab followed by surgery for HER2-positive resectable gastric or esophagogastric junction adenocarcinoma with extensive lymph node metastasis: Japan Clinical Oncology Group study JCOG1301C (Trigger Study).

Abstract

BACKGROUND:

This randomized phase II study explored the superiority of trastuzumab plus S-1 plus cisplatin (SP) over SP alone as neoadjuvant chemotherapy (NAC) for HER2-positive resectable gastric cancer with extensive lymph node metastasis.

METHODS:

Eligible patients with HER2-positive gastric or esophagogastric junction cancer and extensive lymph node metastasis were randomized to receive three or four courses of preoperative chemotherapy with SP (arm A) or SP plus trastuzumab (arm B). Following gastrectomy, adjuvant chemotherapy with S-1 was administered for 1 year in both arms. The primary endpoint was overall survival, and the sample size was 130 patients in total. The trial is registered with the Japan Registry of Clinical Trials, jRCTs031180006.

RESULTS:

This report elucidates the early endpoints, including pathological findings and safety. The study was terminated early due to slow patient accruals. In total, 46 patients were allocated to arm A (n = 22) and arm B (n = 24). NAC was completed in 20 patients (91%) in arm A and 23 patients (96%) in arm B, with similar incidences of grade 3-4 hematological and non-hematological adverse events. Objective response rates were 50% in arm A and 84% in arm B (p = 0·065). %R0 resection rates were 91% and 92%, and pathological response rates (≥ grade 1b in Japanese classification) were 23% and 50% (p = 0·072) in resected patients, respectively.

CONCLUSIONS:

Trastuzumab can be safely added to platinum-containing doublet chemotherapy as NAC, and it has the potential to contribute to higher antitumor activity against locally advanced, HER2-positive gastric or esophagogastric junction cancer with extensive nodal metastasis.

• Authors: Masanori Tokunaga, Nozomu Machida, Junki Mizusawa, Seiji Ito, Hiroshi Yabusaki, Motohiro Hirao, Masaya Watanabe, Hiroshi Imamura, Takahiro Kinoshita, Takushi Yasuda, Jun Hihara, Haruhiko Fukuda, Takaki Yoshikawa, Narikazu Boku, Masanori Terashima
• Journal: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association (Gastric Cancer) Vol. 27 Issue 3 Pg. 580-589 (May 2024) ISSN: 1436-3305 [Electronic] Japan
• PMID: 38243037 (Publication Type: Randomized Controlled Trial, Clinical Trial, Phase II, Journal Article)
• Copyright: © 2024. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.

Chemical References

• Trastuzumab
• Receptor, ErbB-2

Topics

• Humans
• Trastuzumab (therapeutic use)
• Stomach Neoplasms (drug therapy, surgery, pathology)
• Lymphatic Metastasis (pathology)
• Japan
• Receptor, ErbB-2
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Esophagogastric Junction (pathology)
• Adenocarcinoma (drug therapy, surgery, pathology)
• Medical Oncology
• Neoadjuvant Therapy
• Esophageal Neoplasms