A phase II trial of trastuzumab combined with irinotecan in patients with advanced HER2-positive chemo-refractory gastric cancer: Osaka Gastrointestinal Cancer Chemotherapy Study Group OGSG1203 (HERBIS-5)

Aim/Background

Irinotecan is a key drug in second- or further-line chemotherapy for patients with advanced gastric cancer. We assessed the efficacy and safety of combination chemotherapy with trastuzumab and irinotecan in Japanese patients with advanced HER2-positive chemo-refractory gastric cancer.

Methods

Intravenous infusion of irinotecan every 2 weeks at a dose of 150 mg/m²; intravenous infusion of trastuzumab at a dose of 8 mg/kg on day 1 of the first cycle, followed by 6 mg/kg every 3 weeks. Administration of irinotecan and trastuzumab were repeated in independent schedules. The primary endpoint was disease control rate. The secondary endpoints were adverse events, overall response rate, time-to-treatment failure, progression-free survival, overall survival, and response rate stratified by prior trastuzumab use. This study was conducted by the Osaka Gastrointestinal Cancer Chemotherapy Study Group (OGSG).

Results

From October 2012 to Augst 2014, 30 patients were enrolled and one patient withdrew before study treatment. Accordingly, 29 patients were assessable for efficacy and safety. The disease control rate was 65.5% [95% C.I. 45.7 - 82.1%], and the response rate was 20.7% [95% C.I. 8.0 - 39.7%]. The median progression-free survival time was 3.7 months [95% C.I. 3.1 - 5.5 months]. The major grade 3/4 toxic effects were neutropenia (24%), anemia (24%), leucopenia (21%), anorexia (11%), fatigue (14%), hypoalbuminemia (24%), and hypokalemia (14%). One death were considered to be related to the study.

Conclusions

These findings indicated that the combination trastuzumab with irinotecan is feasible and showed promising efficacy against advanced HER2-positive chemo-refractory gastric cancer.

Clinical trial identification

Osaka Gastrointestinal Cancer Chemotherapy Study Group OGSG1203 (HERBIS-5)

Disclosure

All authors have declared no conflicts of interest.