In a Korean phase Ib/II trial reported in the Journal of Clinical Oncology, Kim et al found that trastuzumab combined with ramucirumab and paclitaxel showed activity in the second-line treatment of patients with HER2-positive advanced gastric or gastroesophageal junction cancer whose disease progressed after prior therapy with trastuzumab plus chemotherapy.
Study Details
The multicenter trial involved 50 patients treated with the recommended phase II dose of paclitaxel at 80 mg/m2 on days 1, 8, and 15; trastuzumab at a loading dose of 4 mg/kg on day 1 cycle 1 followed by 2 mg/kg weekly; and ramucirumab at 8 mg/kg on days 1 and 15 every 4 weeks. No dose-limiting toxicities were observed at any dose level during phase Ib of the trial. The primary endpoint for the phase II portion was investigator-assessed progression-free survival among patients treated with the phase II dose.
Key Findings
Median follow-up among the 50 patients was 27.5 months (95% confidence interval [CI] = 17.4–37.6 months). Median progression-free survival was 7.1 months (95% CI = 4.8–9.4 months); median overall survival was 13.6 months (95% CI = 9.4–17.7 months), with a 1-year rate of 55.3% (95% CI = 41.1%–69.5%).
Objective response was observed in 27 patients (54%, 95% CI = 39%–68%), including complete response in 1 (2%). With six patients remaining on treatment at data cutoff, median duration of response was 6.7 months (95% CI = 1.5–11.9 months). Stable disease was observed in an additional 21 patients (42%), yielding a disease control rate of 96%.
After first-line treatment, loss of HER2 expression was observed in 8 (34.8%) of 23 evaluated patients. No definitive associations between HER2 expression and outcomes were observed.
The most common treatment-related adverse events of any grade were neutropenia (64%), peripheral sensory neuropathy (32%), anorexia (32%), and anemia (30%). Grade 3 or 4 treatment-related adverse events occurred in 35 patients (70%), most commonly neutropenia (in 52%) and grade 3 febrile neutropenia (in 2%). No treatment-related deaths were observed.
The investigators concluded, “Trastuzumab combined with ramucirumab and paclitaxel showed appreciable efficacy with manageable safety profiles in patients with previously treated HER2-positive gastric or gastroesophageal junction cancer.”
Sun Young Rha, MD, PhD, of the Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Celltrion, Inc; Lilly, Inc; and Samyang, Inc, and by the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea. For full disclosures of the study authors, visit ascopubs.org.
