SB3 Proves Comparable Cardiovascular Safety to Reference Trastuzumab

Data from a prespecified secondary analysis of phase 3 clinical trial suggests the trastuzumab biosimilar, SB3, demonstrated cardiac safety and survival comparable to those receiving the reference agent for up to 6 years follow-up.

Results of the study, which included 538 women, results indicate there were no differences in event-free survival (EFS) and overall survival (OS) between treatment groups within the study and there were also no reports of symptomatic cardiac failure or death due to a cardiovascular event.¹

“In this secondary analysis of a randomized clinical trial, cardiac events were rarely reported in both treatment groups," wrote investigaotrs. The EFS and OS were comparable between patients treated with SB3 and [reference trastuzumab] with ERBB2-positive early or locally advanced breast cancer up to 6 years of follow-up. These long-term results provide further evidence supporting the similarity of SB3 and [reference trastuzumab].”

The advent of biosimilars brought the promise of reduced cost and represented a major leap towards equity. As this field begun to gain steam, chemotherapy-related cardiotoxicity began to gain recognition as a risk factor. The current study was designed as a secondary analysis of a randomized clinical trial comparing trastuzumab bio similar SB3 to reference trastuzumab for treatment of ERBB2-positive early or locally advanced breast cancer.¹

In the original trial, patients were randomized to either SB3 or reference trastuzumab with concomitant neoadjuvant chemotherapy for 8 cycles—4 cycles of docetaxel followed by 4 cycles of fluorouracil, epirubicin, and cyclophosphamide. After surgery, patients included in the multicenter, double-blind, parallel-group, equivalence phase 3 trial continued SB3 or reference trastuzumab monotherapy for 10 cycles of adjuvant treatment per previous treatment allocation. Investigators noted patients were monitored for up to 5 years after neoadjuvant and adjuvant treatment.¹

The primary outcomes of interest for the analysis were the incidence of symptomatic congestive heart failure and asymptomatic, significant decrease in left ventricular ejection fraction (LVEF). The secondary outcomes of interest were EFS and OS.¹

The 538-patient cohort had a median age of 51 (range, 22-65) years and the median 68 (range 8.5-78.1) months. Investigators noted baseline characteristics were comparable between the treatment groups and cardiac safety was monitored among 367 patients, including 186 receiving SB3 and 181 receiving reference trastuzumab. Initial analysis indicated asymptomatic, clinically significant LVEF decreases were rarely reported during the trial, with these decreases occurring among 0.4% of the SB3 group and 0.7% of the reference trastuzumab group.¹

Overall, survival was evaluated for the 367 patients in the cardiac safety cohort and an additional 171 patients rolled after a protocol amendment. Results of this analysis suggested there were no differences for EFS (HR, 0.84 [95% CI, 0.58-1.20]; P=.34) or OS (HR, 0.61 [95% CI, 0.36-1.05]; P=.07). Further analysis suggested 5-year EFS rates were 79.8% (95%CI, 74.8-84.9) in the SB3 group and 75.0% (95% CI, 69.7-80.3) in the reference trastuzumab group. The 5-year OS rates were 92.5% (95% CI, 89.2-95.7) in the SB3 group and 85.4%(95% CI, 81.0-89.7) in the reference trastuzumab group.¹

In a linked editorial, Gregory S. Calip, PharmD, MPH, PhD, Ivy P. Altomare, MD, and Jenny S. Guadamuz, MSPH, PhD, commended investigators for their work but underlined limitations to consider when interpreting results.²

“The investigators provide important evidence further establishing the comparability of a widely used biosimilar treatment for ERBB2-overexpressing early breast cancer in a sample of predominantly White and Asian patients,” wrote the authors.² “However, this study lacks external validity for Black and Latinx patients, who are at higher risk of cardiovascular toxic effects, have the least access to ERBB2-targeted therapy, and may have the greatest potential benefit from increased affordability.”
References:

1. 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 Netw Open. 2023;6(4):e235822. doi:10.1001/jamanetworkopen.2023.5822
2. Calip GS, Altomare IP, Guadamuz JS. Evaluating External Validity of Oncology Biosimilar Safety Studies. JAMA Netw Open. 2023;6(4):e235776. doi:10.1001/jamanetworkopen.2023.5776