Phase 3 Study Comparing SB3 and Reference Trastuzumab in HER2-Positive, Early or Locally Advanced Breast Cancer in the Neoadjuvant Setting: 4-Year Follow-Up

2020 Year in Review - Biosimilars —January 13, 2021



An ongoing extension study from the phase 3 trial of trastuzumab biosimilar SB3 and trastuzumab reference supports similarity in terms of long-term cardiac safety and survival in patients with HER2-positive, early or locally advanced breast cancer.

A randomized phase 3 trial demonstrated the similarity of the biosimilar SB3 to its reference trastuzumab as neoadjuvant therapy in patients with human epidermal growth factor receptor 2 (HER2)-positive early or locally advanced breast cancer.1 At the 2020 American Society of Clinical Oncology Annual Meeting, 4-year follow-up results of an ongoing extension study (NCT02771795) in a subset of patients enrolled in this phase 3 trial assessing the long-term cardiac safety and survival outcomes were presented.2

The primary objective was to observe the incidence of symptomatic congestive heart failure (CHF) and asymptomatic significant left ventricular ejection fraction (LVEF) decrease; secondary outcomes were event-free survival (EFS), defined as time from randomization to incidence of recurrence, progression, or death, and overall survival (OS).2 Ad-hoc analyses included EFS and OS analysis by antibody-dependent cell-mediated cytotoxicity (ADCC) status in drifted (patients exposed to ≥1 vials from trastuzumab lots with a downward drift during the neoadjuvant period) and nondrifted trastuzumab (patients who were never exposed to any vials from a drifted trastuzumab lost during the neoadjuvant period) groups.2

A total of 367 patients of the 875 patients randomized in the phase 3 trial were enrolled in the extension study; of these, 186 patients received SB3 and 181 were treated with trastuzumab.2 The median follow-up (from date of informed consent for the phase 3 study) was 53 months. Demographic and disease characteristics were similar between the treatment groups.2

During the follow-up period after adjuvant therapy, there were 2 reports of asymptomatic significant LVEF decrease in the trastuzumab group and 1 in the SB3 group; all 3 patients recovered with LVEF ≥50%.2 No symptomatic CHF, cardiac death, or other significant cardiac condition was reported during the follow-up period.2

In terms of efficacy, 4-year EFS and OS rates were similar between the 2 groups.2 The 4-year EFS rate was 83.4% in the SB3 group and 80.7% in the trastuzumab group (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.47-1.27); 4-year OS rates were 94.4% and 89.6%, respectively (HR, 0.53; 95% CI, 0.24-1.16). Ad-hoc analysis showed a statistical difference in EFS and OS between nondrifted trastuzumab and drifted trastuzumab groups, but not between the SB3 and nondrifted trastuzumab groups.2

The 4-year follow-up results in a subset of patients from the phase 3 trial support the comparable long-term cardiac safety and survival between SB3 and trastuzumab reference in patients with HER2-positive early or locally advanced breast cancer that was previously reported.3 Ad-hoc analysis indicates a possible correlation between ADCC status and survival outcomes.

1. Pivot X, et al. J Clin Oncol. 2018;36:968-974.
2. Pivot X, et al. ASCO 2020. Abstract 578.
3. Pivot X, et al. Eur J Cancer. 2019;120:1-9.

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Last modified: January 13, 2021

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