Four-year follow-up of a phase III study comparing SB3 (trastuzumab biosimilar) and reference trastuzumab in HER2-positive early or locally advanced breast cancer in neoadjuvant setting.

Abstract

578 Background: SB3 was approved in the US and EU as a biosimilar of reference trastuzumab (TRZ). Here, we report 4-year cardiac safety and survival outcomes. Methods: After completing neoadjuvant-adjuvant therapy in patients with HER2 positive early breast cancer, patients from selected countries participated in a 5-year follow-up study of a phase III trial (Pivot et al. Eur J Cancer 2019). The aim was to observe long-term cardiac safety and survival. EFS and OS were analyzed in subgroups by ADCC status within TRZ in ad-hoc analyses. Results: Of 875 patients randomized in the phase III trial, 367 patients (SB3, N=186; TRZ, N=181) were enrolled in the follow-up study. The median follow-up was 53 months. During the follow-up, the incidence of asymptomatic significant left ventricular ejection fraction (LVEF) decrease was low (SB3, n=1; TRZ, n=2), with all patients recovering with LVEF ≥ 50%. No cases of symptomatic congestive heart failure, cardiac death, or other significant cardiac condition were reported. 4-year EFS rates were 83.4% for SB3 and 80.7% for TRZ with a HR of 0.77 [95% CI 0.47, 1.27]. 4-year OS rates were 94.3% for SB3 and 89.6% for TRZ with a HR of 0.53 [95% CI 0.24, 1.16]. From ad-hoc analysis, a difference in EFS and OS was seen between Non-drifted TRZ and Drifted TRZ; Difference between SB3 and Non-drifted TRZ was not statistically significant. Conclusions: In a subset of patients from the phase III trial, comparable long-term cardiac safety and survival at 4-year supports biosimilarity between SB3 and TRZ. Ad-hoc analysis results by ADCC status suggest a possible correlation between ADCC and clinical efficacy. Further follow-up is needed. Clinical trial information: NCT02771795 . [Table: see text]