HELOISE: Phase IIIb randomized multicenter study comparing standard-of-care and higher-dose trastuzumab regimens combined with chemotherapy as first-line therapy in patients with human epidermal growth factor receptor 2–positive metastatic gastric or gastroesophageal junction adenocarcinoma

Manish A. Shah, Rui hua Xu, Yung Jue Bang, Paulo M. Hoff, Tianshu Liu, Luis A. Herráez-Baranda, Fan Xia, Amit Garg, Mona Shing, Josep Tabernero

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60 Citations (Scopus)

Abstract

© 2017 by American Society of Clinical Oncology. Purpose: To compare standard-of-care (SoC) trastuzumab plus chemotherapy with higher-dose (HD) trastuzumab plus chemotherapy to investigate whether HD trastuzumab increases trastuzumab serum trough concentration (C trough ) levels and increases overall survival (OS) in first-line human epidermal growth factor receptor 2–positive metastatic gastric or gastroesophageal junction adenocarcinoma. Patients and Methods: Patients with Eastern Cooperative Oncology Group performance status 2, no prior gastrectomy, and ≥ two metastatic sites were randomly assigned at a one-to-one ratio to loading-dose trastuzumab 8 mg/kg followed by SoC trastuzumab maintenance 6 mg/kg every 3 weeks or loading-dose trastuzumab 8 mg/kg followed by HD trastuzumab maintenance 10 mg/kg every 3 weeks until progression; treatment in each arm was combined with cisplatin 80 mg/m 2 plus capecitabine 800 mg/m 2 twice per day in cycles 1 to 6. The primary objective was HD trastuzumab OS superiority (all randomly assigned patients [full-analysis set]). Final results are from an interim analysis for futility (boundary hazard ratio [HR] ≥ 0.95) at 125 deaths. Results: At clinical cutoff, 248 patients had been randomly assigned. A marked increase in mean trastuzumab C trough was observed after the first HD trastuzumab cycle versus SoC trastuzumab. In the full-analysis set, median OS was 12.5 months in the SoC trastuzumab arm and 10.6 months in the HD trastuzumab arm (stratified HR, 1.24; 95% CI, 0.86 to 1.78; P = .2401). Results were similar in the per-protocol set (cycle 1 trastuzumab C trough < 12 μg/mL). Safety was comparable between arms. Conclusion: HD 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 SoC for first-line treatment of human epidermal growth factor receptor 2–positive metastatic gastric or gastroesophageal junction adenocarcinoma.
Original languageEnglish
JournalJournal of Clinical Oncology
Volume35
Issue number22
DOIs
Publication statusPublished - 1 Aug 2017

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