High-Dose First-Line Trastuzumab Maintenance in Metastatic HER2-Positive Gastric Cancer
As reported in the Journal of Clinical Oncology by Shah et al, the phase IIIB HELOISE trial has shown no survival benefit of high-dose vs standard trastuzumab (Herceptin) maintenance plus chemotherapy in the first-line treatment of metastatic gastric or gastroesophageal junction adenocarcinoma.
Study Details
In the open-label trial, 248 patients with no prior gastrectomy and ≥ 2 metastatic sites from 74 centers in 23 countries were randomized between December 2011 and February 2015 (clinical cutoff date) to receive a trastuzumab loading dose of 8 mg/kg followed by standard trastuzumab maintenance at 6 mg/kg every 3 weeks (n = 124) or high-dose maintenance at 10 mg/kg every 3 weeks (n = 124) combined with cisplatin at 0 mg/m2 every 3 weeks and capecitabine at 800 mg/m2 twice per day in cycles 1 to 6. Randomization was stratified by measurable vs nonmeasurable/nonevaluable disease, geographic region (in United States vs outside United States), and creatinine clearance. Predose samples were obtained to measure trastuzumab serum trough concentrations.
The primary endpoint was overall survival in all randomized patients (full analysis set). The current report provides final results of the study, which are from a preplanned interim analysis for futility (boundary hazard ratio [HR] ≥ 0.95) at 125 deaths.
No Improvement in Overall Survival
At the interim analysis, the overall survival futility boundary was crossed, and the study was stopped on the recommendation of an independent data monitoring committee. Trough serum trastuzumab concentrations were markedly increased in the high-dose group after the first maintenance dose (mean 35.3 vs 19.2 µg/mL) and after 6 cycles (mean 58.1 vs 31.4 µg/mL).
Median overall survival was 10.6 months in the high-dose group vs 12.5 months in the standard-dose group (stratified HR = 1.24, P = .2401). Among 65 patients with cycle 1 trastuzumab trough concentrations < 12 µg/mL (per-protocol set), median overall survival was 9.4 months in high-dose patients vs 10.8 months in standard-dose patients (stratified HR = 1.00, P = .9931). In the full-analysis set, median progression-free survival was 5.6 months in the high-dose group vs 5.7 months in the standard-dose group (stratified HR = 1.04, P = .8222).
Adverse Events
Safety was comparable in the two groups. The most common adverse events of any grade in the high-dose and standard-dose groups were nausea (39% vs 42%), vomiting (33% vs 27%), neutropenia (48% vs 47%), and anemia (29% vs 32%). Adverse events led to discontinuation of any study drug in 15% vs 7%.
The investigators concluded: “[High-dose] trastuzumab maintenance dosing was associated with higher trastuzumab concentrations, no increased efficacy, and no new safety signals. HELOISE confirms standard-dose trastuzumab (loading dose of 8 mg/kg followed by 6 mg/kg maintenance dose every 3 weeks) with chemotherapy as the [standard of care] for first-line treatment of human epidermal growth factor receptor 2–positive metastatic gastric or gastroesophageal junction adenocarcinoma.”
The study was supported by F. Hoffmann-La Roche Ltd.
Manish A. Shah, MD, of NewYork-Presbyterian/Weill Cornell Medical Center, is the corresponding author of the Journal of Clinical 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®.
