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.
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