Trastuzumab biosimilar ABP 980 is as safe as reference product in terms of cardiac toxicity in patients enrolled in the long-term LILAC study

Article Title: Cardiac Safety of the Trastuzumab Biosimilar ABP 980 in Women with HER2-Positive Early Breast Cancer in the Randomized, Double-Blind, Active-Controlled LILAC Study

Citation: Kolberg H-C et al. Drug Safety 2020;43:233–42

Publication date: January 2020

Abstract published: August 2021
Cardiotoxicity is the most important limitation in the application of trastuzumab, and one of the most important parameters to monitor when assessing the safety of a trastuzumab biosimilar.

Trastuzumab (Herceptin®) is the gold standard of care for people with early and metastatic breast cancers and metastatic gastric cancer overexpressing human epidermal growth factor receptor 2 (HER2). The phase III LILAC trial demonstrated ABP 980 had biosimilarity to trastuzumab reference product (RP) in women with HER2-positive early breast cancer, with no clinically meaningful difference between the two products. Based on the totality of evidence, ABP 980 was approved by the European Medicines Agency (EMA), and subsequently by the FDA, for the same indications as trastuzumab RP.

Cardiac toxicity is a rare but serious concern with trastuzumab; possibly related to HER2 blockade. In the LILAC study, patients were randomized to receive neoadjuvant ABP 980 or trastuzumab RP for 4 cycles prior to surgical resection, and consolidation treatment with either drug given every 3 weeks for up to 1 year thereafter. To monitor cardiac safety, an electrocardiogram and 2-D echocardiogram were performed at all visits.

Overall, no marked decline of left ventricular ejection fraction (LVEF) was observed. In patients who received ABP 980 or trastuzumab RP throughout the study and those who were switched from trastuzumab RP to ABP 980 in the adjuvant (postoperative) phase, LVEF decline (10–50%) was seen in 2.8%, 3.3%, and 3.5% of patients, respectively. There were no meaningful differences between treatment arms. Moreover, incidence of cardiac failure was comparable among the three groups: 2.2%, 0.5%, and 1.2%, respectively. The majority of LVEF decline cases were asymptomatic, and most patients exhibiting LVEF decline during the 1-year study had pre-existing cardiovascular conditions at baseline, including hypertension and arrhythmias. Most cardiac failure reports were grade 1 or 2, although none were classified a serious adverse event.

The LILAC study revealed a low incidence of cardiac toxicity following 1-year treatment with trastuzumab biosimilar ABP 980, with no clinically meaningful difference in the rate of LVEF decline between treatment arms. Cardiotoxicity is the most important limitation in the application of trastuzumab. Hence the acceptable safety and tolerability profile observed in this study suggests ABP 980 may be a useful choice in patients starting treatment or when considering switching from trastuzumab RP.

Key takeaway

Trastuzumab is the gold standard of treatment for HER2-expressing cancers, although it is associated with an increased cardiac toxicity risk. The biosimilar, ABP980, demonstrated biosimilarity to the reference product, suggesting no increased risk from switching to the trastuzumab biosimilar.