Effect of a proposed trastuzumab biosimilar compared with trastuzumab on overall response rate in patients with ERBB2 (HER2)-positive metastatic breast cancer: A randomized clinical trial

IMPORTANCE Treatment with the anti-ERBB2 humanized monoclonal antibody trastuzumab and chemotherapy significantly improves outcome in patients with ERBB2 (HER2)-positive metastatic breast cancer; a clinically effective biosimilar may help increase access to this therapy. OBJECTIVE To compare the overall response rate and assess the safety of a proposed trastuzumab biosimilar plus a taxane or trastuzumab plus a taxane in patients without prior treatment for ERBB2-positivemetastatic breast cancer. DESIGN, SETTING, AND PARTICIPANTS Multicenter, double-blind, randomized, parallel-group, phase 3 equivalence study in patients with metastatic breast cancer. From December 2012 to August 2015, 500 patients were randomized 1:1 to receive a proposed biosimilar or trastuzumab plus a taxane. Chemotherapy was administered for at least 24 weeks followed by antibody alone until unacceptable toxic effects or disease progression occurred. INTERVENTIONS Proposed biosimilar (n = 230) or trastuzumab (n = 228) with a taxane. MAIN OUTCOMES AND MEASURES The primary outcomewasweek 24 overall response rate (ORR) defined as complete or partial response. Equivalence boundaries were 0.81 to 1.24 with a 90% CI for ORR ratio (proposed biosimilar/trastuzumab) and -15%to 15%with a 95% CI for ORR difference. Secondary outcome measures included time to tumor progression, progression-free and overall survival at week 48, and adverse events. RESULTS Among500women randomized, the intention-to-treat population included 458 women (mean [SD] age, 53.6 [11.11] years) and the safety population included 493women. TheORRwas 69.6%(95%CI, 63.62%-75.51%) for the proposed biosimilar vs 64.0%(95%CI, 57.81%-70.26%) for trastuzumab. TheORRratio (1.09;90%CI,0.974-1.211) andORRdifference (5.53; 95%CI, -3.08 to 14.04)were within the equivalence boundaries.Atweek 48, therewas no statistically significant difference with the proposed biosimilar vs trastuzumab for time to tumor progression (41.3%vs 43.0%; -1.7%; 95%CI, -11.1%to 6.9%), progression-free survival (44.3% vs 44.7%; -0.4%; 95%CI, -9.4%to 8.7%), or overall survival (89.1%vs 85.1%; 4.0%; 95%CI, -2.1%to 10.3%). In the proposed biosimilar and trastuzumab groups, 239 (98.6%) and 233 (94.7%) had at least 1 adverse event, the mostcommonincluding neutropenia (57.5%vs 53.3%), peripheral neuropathy (23.1%vs 24.8%), and diarrhea (20.6%vs 20.7%). CONCLUSIONS AND RELEVANCE Amongwomen with ERBB2-positivemetastatic breast cancer receiving taxanes, the use of a proposed trastuzumab biosimilar compared with trastuzumab resulted in an equivalent overall response rate at 24 weeks. Further study is needed to assess safety and long-term clinical outcome.