Ado-trastuzumab Emtansine vs Taxane in HER2-Positive Advanced Gastric Cancer
The adaptive phase II/III GATSBY trial has shown no survival difference between ado-trastuzumab emtansine (Kadcyla) vs taxane treatment in patients with previously treated locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma. Results were reported by Thuss-Patience et al in The Lancet Oncology.
Study Details
In stage 1 of the open-label trial, conducted at 107 sites in 28 countries, patients whose disease had progressed during or after first-line therapy were randomized 2:2:1 between September 2012 and October 2013 to receive ado-trastuzumab emtansine at 3.6 mg/kg every 3 weeks (n = 70) or at 2.4 mg/kg weekly (n = 75) or physician’s choice of docetaxel at 75 mg/m² every 3 weeks or paclitaxel at 80 mg/m² weekly (n = 37). At a preplanned interim analysis in October 2013, the independent data monitoring committee selected ado-trastuzumab emtansine at 2.4 mg/kg weekly as the dose to proceed to stage 2 of the trial.
By February 2015, an additional 153 patients had been randomized 2:1 to receive ado-trastuzumab emtansine at 2.4 mg/kg weekly (total n = 228) and a further 80 patients to receive taxane treatment (total n = 117); among the 111 patients who received at least 1 taxane dose, 69 received docetaxel, 41 received paclitaxel, and 1 received both. The primary endpoint was overall survival in the intent-to-treat population.
For the ado-trastuzumab emtansine vs taxane groups, median age was 62 years in both (39% vs 42% ≥ 65 years), 78% vs 81% were male, 48% vs 49% were white and 46% in both were Asian, the primary disease site was the stomach in 66% vs 72% and the gastroesophageal junction in 34% vs 28%, 96% vs 97% had metastatic disease, and previous anti-HER2 therapy included trastuzumab (Herceptin) in 76% vs 79%.
Overall Survival
Median follow-up was 17.5 months in the ado-trastuzumab emtansine group and 15.4 months in the taxane group. Median overall survival was 7.9 months vs 8.6 months (hazard ratio [HR] = 1.15, P = .86). No clinical or biomarker subgroups exhibited a survival benefit with ado-trastuzumab emtansine vs taxane treatment. Median progression-free survival was 2.7 months vs 2.9 months (HR = 1.13, P = .31). Objective response rates were 20.6% vs 19.6%.
Following disease progression, 54% and 56% of patients received subsequent anticancer therapy. A sensitivity analysis censoring patients at the time of initiation of a new treatment showed no difference in overall survival (median 8.1 vs 9.4 months, HR = 1.34, 95% confidence interval = 0.88–2.05).
Adverse Events
Grade ≥ 3 adverse events occurred in 60% of the ado-trastuzumab emtansine group and 70% of the taxane group; the most common adverse events were anemia (26%) and thrombocytopenia (11%) in the ado-trastuzumab emtansine group and neutropenia (39%) and anemia (18%) in the taxane group. Serious adverse events occurred in 29% vs 28%, with the most common being anemia (4%), upper gastrointestinal hemorrhage (4%), pneumonia (3%), gastric hemorrhage (3%), and gastrointestinal hemorrhage (2%) in the ado-trastuzumab emtansine group and pneumonia (4%), febrile neutropenia (4%), anemia (3%), and neutropenia (3%) in the taxane group.
Adverse events led to treatment discontinuation in 14% of each group. Death due to adverse events occurred in 4% of each group.
The investigators concluded: “[Ado-]trastuzumab emtansine was not superior to taxane in patients with previously treated, HER2-positive advanced gastric cancer. There is still an unmet need in this patient group and therapeutic options remain limited.”
The study was funded by F. Hoffmann-La Roche.
Yoon-Koo Kang, MD, of the Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea, is the corresponding author of The Lancet Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
