A Phase II Trial of Trastuzumab Combined With Irinotecan in Patients With Advanced HER2-positive Chemotherapy-refractory Gastric Cancer (OGSG1203 HERBIS-5): Final Results.

Background/aim: Irinotecan is a key drug for patients with advanced gastric cancer. We assessed the efficacy and safety of combination chemotherapy with trastuzumab and irinotecan in patients with advanced human epidermal growth factor receptor type 2 (HER2)-positive chemotherapy-refractory gastric cancer.

Patients and methods: Eligibility criteria included unresectable or recurrent HER2-positive gastric cancer patients who were refractory to at least one regimen of chemotherapy. Irinotecan was administered at a dose of 150 mg/m² every 2 weeks, and trastuzumab at a dose of 8 mg/kg on day 1 of the first cycle, followed by 6 mg/kg every 3 weeks. The primary endpoint was the disease control rate (DCR). The secondary endpoints were adverse events (AEs), overall response rate (ORR), time-to-treatment failure (TTF), progression-free survival (PFS), and overall survival (OS).

Results: Thirty patients were enrolled, of whom 18 previously received a single chemotherapy regimen whereas 12 received two or more regimens. As one patient withdrew before the study treatment, 29 patients were assessable for efficacy and safety. The DCR was 65.5%, and the ORR was 20.7%. The median PFS and OS were 3.7 and 7.5 months, respectively. The major grade 3/4 AEs were neutropenia (24%), anemia (24%), leukopenia (21%), anorexia (11%), fatigue (14%), hypoalbuminemia (24%), and hypokalemia (14%). One treatment-related death occurred.

Conclusion: These findings indicate that irinotecan plus trastuzumab is feasible with modest potential efficacy against chemotherapy-refractory advanced HER2-positive gastric cancer.