Cardiac Safety of SB3 Trastuzumab Biosimilar for Patients With HER2-Positive Breast Cancer

With 6 years of follow-up, trastuzumab biosimilar SB3 was found to yield cardiac safety and survival comparable to reference trastuzumab among patients with HER2-positive early or locally advanced breast cancer.

The monoclonal antibody trastuzumab “has been the standard of care for the treatment of patients with [HER2]-positive breast cancer and [HER2]-positive advanced gastric cancer due to its effectiveness and favorable toxicity profile,” wrote Xavier Pivot, MD, PhD, Institut de Cancérologie Strasbourg Europe, Strasbourg, France, and coauthors. However, there have been reports of cardiac events more frequently with trastuzumab, leading to routine cardiac monitoring suggested for patients. SB3 is a “widely approved trastuzumab biosimilar” that demonstrated similar efficacy to trastuzumab.

This secondary analysis of a phase 3 clinical trial included 367 patients with HER2-positive early or locally advanced breast cancer randomly assigned on a 1-to-1 basis to receive either SB3 biosimilar (n = 186) or trastuzumab (n = 181), plus concomitant neoadjuvant chemotherapy for 8 cycles. The study was terminated early due to increased risk of COVID exposure, as patients were required to visit sites for cardiac assessments. The primary end point of the study was incidence of symptomatic congestive heart failure and asymptomatic significant LVEF decrease (defined as a decrease of 10% or more from baseline with a resulting value >50%). Secondary end points included incidence of any death due to cardiovascular event and other significant cardiac conditions, event-free survival, and overall survival.

Patients were monitored for 5 years after the last administration of either SB3 or trastuzumab. The baseline median LVEF was 65% in both arms, and the changes from baseline were comparable between the two arms with the lowest median LVEF during the follow-up period as 60% in both arms. There was 1 patient in the SB3 arm and 2 patients in the trastuzumab arm who experienced asymptomatic clinically significant LVEF decrease. There were no instances of symptomatic cardiac failure or death due to any cardiovascular event. The 5-year event-free survival rates were 79.8% in the SB3 arm and 75.0% in the trastuzumab arm. The overall survival rates were 92.5% in the SB3 arm and 85.4% in the trastuzumab arm.

Dr Pivot and coauthors concluded, “Overall, the cardiac safety profile of patients treated with SB3 was comparable to that of patients treated with [trastuzumab].” They went on to say that these results “provide additional evidence that SB3 has no clinically meaningful difference compared with [trastuzumab].”

Source:

Pivot X, Cortés J, Lüftner D, et al. Cardiac safety and efficacy of SB3 trastuzumab biosimilar for ERBB2-positive early breast cancer: Secondary analysis of a randomized clinical trial. JAMA Network Open. 2023;6(4):e235833. doi:10.1001/jamanetworkopen.2023.5822