Amgen's Trastuzumab Biosimilar, Kanjinti, Clinically Similar to Herceptin in Cardiac Safety

Despite trastuzumab’s utility in treating HER2-positive breast cancer, one of its limitations is cardiotoxicity that can, in some patients, lead to severe heart failure.

During this week’s 2019 American Society of Clinical Oncology Annual Meeting, researchers reported on the cardiac safety of Amgen’s biosimilar trastuzumab, ABP 980 (approved in the European Union under the name Kanjinti), versus the reference trastuzumab, Herceptin.

These new safety data derive from the LILAC study; in findings that have been reported previously, LILAC, which notably used pathological complete response (pCR) as its primary endpoint, demonstrated that there were no clinically meaningful differences between the biosimilar and its reference. these findings, together with analytical and other data, supported the biosimilar’s authorization by the European Commission.

The data presented this week reported that, in the neoadjuvant phase, all 725 enrolled patients received 4 cycles of chemotherapy were then randomized to receive either the biosimilar (n = 364) or reference (n = 361) trastuzumab.¹ After surgery, those randomized to the biosimilar continued to receive the biosimilar for up to 1 year. Those randomized to the reference either continued the reference (n = 190) or switched to the biosimilar (n = 171) and were treated for up to 1 year. Adverse events were assessed every 3 weeks, and cardiac safety was assessed every 3 months.

Cardiac safety was monitored by a computerized 12-lead electrocardiogram, and left ventricular ejection fraction (LVEF) was measured by 2-dimensional echocardiography. LVEF decline was defined as a decrease from baseline by 10 or more percentage points and to less than 50%.

Throughout the course of the study, 22 patients (3.1%) had LVEF decline compared with baseline. No meaningful differences were found between groups: 2.8% of those in the biosimilar-only group, 3.3% of those in the reference-only group, and 3.5% of those in the switch group had LVEF decline. One grade 3 cardiac failure was reported in the switch group. Another cardiac failure in the reference group was coincident with LVEF decline. No patients discontinued therapy due to cardiac failure.

These data from LILAC, write the investigators, further confirm the tolerability of the biosimilar, and no new safety signals arose whether patients were treated with the biosimilar only or switched from the reference.

In an interview with The Center for Biosimilars^® following presentation of the data, Hans-Christian Kolberg, MD, lead author of the study, discussed how LILAC’s results are uniquely poised to build confidence among providers who may treat their patients with the biosimilar.

“What was special about the LILAC study,” he said, was that “it is the only study worldwide, the first and only study in a multicenter setting, that did a pCR central review…it was really difficult, but it paid."

LILAC was also the only registration study for a trastuzumab product, Kolberg noted, that included a switch to the biosimilar among some of the patients who initiated therapy with the reference trastuzumab. “People may have to switch during therapy, [and LILAC] is the only study that shows that this is safe and feasible, so that was the special thing about that.”

The cardiac findings from the LILAC trial presented at this year’s meeting, Kolberg added, are also crucial to providing reassurance that treatment with the biosimilar will not result in increased cardiotoxicity. “Saving money is of course important,” he said, “but it also has to be safe. And we could show here that cardiac events were completely the same.”

Reference

1. Kolberg HC, Colleoni M, Demetriou G, et al. Cardiac safety of the trastuzumab biosimilar ABP 980 in women with HER2-positive early breast cancer in the LILAC study. Presented at: American Society of Clinical Oncology Annual Meeting 2019; May 31-June 4, 2019; Chicago, Illinois. Abstract 557.