Equivalence study to compare the effects of ABP 980 biosimilar versus reference trastuzumab shows similar pathologic response rates in women with HER2-positive early breast cancer in neoadjuvant setting

A large body of experience shows trastuzumab is safe and effective for neoadjuvant treatment of HER2-positive early breast cancer. This study assessed the biosimilarity of ABP 980 and reference trastuzumab in terms of efficacy, safety, and immunogenicity and thereby sought to add to the existing totality of evidence from analytical, functional, and pharmacokinetic studies for ABP 980.

Trastuzumab is the gold standard of care in many countries for patients with HER2-overexpressing breast cancers. The biosimilar ABP 980 has demonstrated analytical similarity to trastuzumab with respect to structure, function, and pharmacokinetic profile; this randomised study was performed to assess the two drugs’ clinical similarity, as well as the safety and efficacy of switching between originator and biosimilar, in women with operable HER2-positive early breast cancer.

Enrolled patients were divided into three groups: a loading dose and three cycles of 3-weekly neoadjuvant ABP 980 or trastuzumab (in combination with chemotherapy) prior to surgery and, thereafter, continued to receive adjuvant ABP 980 (group 1) or trastuzumab (group 2) or were switched from trastuzumab to ABP 980 every 3 weeks (group 3) for a total treatment period of 1 year.

Findings

The rate of patients achieving the primary endpoint (a pathological complete response based on laboratory tests of tumour tissue at time of surgery) in ABP 980 and trastuzumab groups was 48% and 41%, respectively. According to the sensitivity analysis, the risk difference and the relative risk of achieving the primary endpoint were within the predefined equivalence margins. The overall incidence of adverse events in the two treatment groups during both the neoadjuvant and adjuvant phases was similar. Moreover, switching patients from ABP 980 to trastuzumab did not affect safety – incidence of adverse events in the switching group was similar to that in patients who continued to receive trastuzumab in adjuvant phase. No patients in all groups tested positive for neutralizing antibodies.

Safety, efficacy, and clinical outcomes did not differ for ABP 980 and trastuzumab reference product in women with HER2-positive early breast cancer. Similarities continued during the neoadjuvant and adjuvant phases and switching from trastuzumab to ABP 980 did not lead to any new or unexpected safety signals.

Key takeaway

Trastuzumab is the gold standard of care in many countries for patients with HER2-overexpressing breast cancers. The biosimilar ABP 980 has demonstrated analytical similarity to trastuzumab with respect to structure, function, and pharmacokinetic profile; switching from trastuzumab to ABP 980 does not lead to any new or unexpected safety signals.