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

Although the human epidermal growth factor receptor 2 (HER2) blocker trastuzumab is generally well tolerated, cardiotoxicity can be an important therapeutic limitation. Objective. In this prespecified analysis, we compared the cardiac safety of the trastuzumab biosimilar ABP 980 (KANJINTI™) and the trastuzumab reference product (RP; Herceptin^®) in the phase III LILAC study (ClinicalTrials.gov identifier NCT01901146). Methods. In the neoadjuvant phase of LILAC, after run-in chemotherapy, 725 patients were randomized 1:1 to ABP 980 (n =&thinsp;364) or trastuzumab RP (n =&thinsp;361) plus paclitaxel (every 3 weeks [Q3W] or every week [QW]) for four cycles. After surgery, patients continued treatment Q3W for up to 1 year; ABP 980-treated patients continued ABP 980 (ABP 980/ABP 980; n =&thinsp;364), and trastuzumab RP-treated patients either continued on the RP (trastuzumab RP/trastuzumab RP; n =&thinsp;190) or switched to ABP 980 (trastuzumab RP/ABP 980; n =&thinsp;171). Cardiac safety was monitored by computerized 12-lead electrocardiogram, and left ventricular ejection fraction (LVEF) was assessed by two-dimensional (2D) echocardiogram. LVEF decline was defined as LVEF value decrease from study baseline by ≥ 10 percentage points and to < 50%.. Results. Over the entire study, 22 (3.1%) patients had protocol-defined LVEF decline; no meaningful between-group differences were observed (ABP 980/ABP 980: 2.8%; trastuzumab RP/trastuzumab RP: 3.3%; trastuzumab RP/ABP 980: 3.5%). The incidence of cardiac adverse events was low and comparable in the treatment groups. One grade 3 cardiac failure event reported in the trastuzumab RP/ABP 980 arm, and another in the trastuzumab RP/trastuzumab RP arm, were coincident with LVEF decline. One patient discontinued the investigational product during the adjuvant phase because of cardiac failure. Conclusion. These prespecified analyses confirm the tolerability of ABP 980 and demonstrate clinical similarity of ABP 980 and trastuzumab RP with respect to cardiac safety. No new cardiac safety signals were observed whether patients were receiving ABP 980 or switched from the RP to ABP 980.