Long-Term Safety and Effectiveness of PF-05280014 (a Trastuzumab Biosimilar) Treatment in Patients with HER2-Positive Metastatic Breast Cancer: Updated Results of a Randomized, Double-Blind Study.

ABSTRACT

BACKGROUND: PF-05280014 was compared with trastuzumab sourced from the European Union (trastuzumab-EU), each plus paclitaxel, as first-line treatment for human epidermal growth factor receptor 2-positive metastatic breast cancer in a phase III study. Equivalence between treatment groups was demonstrated. OBJECTIVE: The aim of this study was to report long-term safety and overall survival (OS) over 6 years after the first patient was screened. PATIENTS AND METHODS: Randomized patients received intravenous PF-05280014 or trastuzumab-EU, each plus paclitaxel, until objective disease progression. OS, long-term safety, subgroup safety (patients ongoing after day 378), and time-to-treatment discontinuation (TTD) were assessed based on the final statistical analysis plan amended for the ad-hoc analyses. RESULTS: Of 707 randomized patients (n = 352, PF-05280014; n = 355, trastuzumab-EU), 252 (71.6%) in the PF-05280014 and 251 (70.7%) in the trastuzumab-EU group discontinued treatment due to objective progression. Overall, 451 (63.8%) patients completed the study. Between groups (PF-05280014; trastuzumab-EU), estimated median TTDs were 12.25 and 12.06 months (p = 0.692); 61 (17.3%) and 67 (18.9%) patients died; stratified hazard ratio for OS was 0.929 (95% confidence interval 0.656-1.316; p = 0.339); estimated survival rates were 82.3 and 77.4% at 2 years and 77.2 and 75.3% at 3 years. The incidences of treatment-emergent adverse events (TEAEs) overall (98.6%; 96.6%) and for grades ≥3 (41.0%; 43.1%) were comparable between groups. In patients (n = 265; n = 264) ongoing after day 378, the incidences of any TEAEs, grade ≥3 TEAEs, and serious TEAEs were comparable between the treatment groups. CONCLUSION: Long-term safety and OS were consistent with previous results and demonstrated no clinically meaningful differences between treatment groups. TRIAL REGISTRATION ClinicalTrials.gov NCT01989676 (21 November 2013); and EudraCT 2013-001352-34 (18 December 2013).