The trastuzumab biosimilar ABP 980 showed noninferiority to trastuzumab in a large trial of patients with early HER2-positive breast cancer.
The trastuzumab biosimilar ABP 980 showed noninferiority to trastuzumab in a large trial of patients with early HER2-positive breast cancer. Upper bounds of confidence intervals (CIs) were exceeded, meaning that the non-superiority of the biosimilar was not conclusive.
“The trastuzumab biosimilar ABP 980 is analytically similar to trastuzumab with respect to structure, function, and pharmacokinetic profile, which suggests that there should be no clinically meaningful differences between these drugs in efficacy, safety, or immunogenicity,” wrote study authors led by Gunter von Minckwitz, MD, of the German Breast Group in Neu-Isenburg, Germany.
The LILAC study was a randomized trial including 725 patients in 20 countries, primarily Europe and South America. All patients had histologically confirmed invasive early HER2-positive breast cancer. They received 4 cycles of run-in anthracycline-based chemotherapy, and were then assigned to receive either neoadjuvant ABP 980 (358 patients underwent surgery and were assessable for primary endpoint) or neoadjuvant trastuzumab (338 assessable patients). In the trastuzumab group, 171 patients were randomized to continue to adjuvant trastuzumab, while the other 171 switched to adjuvant ABP 980. The results were published in Lancet Oncology.
A total of 172 patients (48%) in the neoadjuvant ABP 980 group achieved a pathologic complete response, compared with 137 patients (41%) randomized to receive neoadjuvant trastuzumab. The risk difference of pathologic complete response was 7.3%, and risk ratio was 1.188 (90% CI, 1.033–1.366). The primary endpoint was not met, because the upper boundaries of the 90% CIs for risk difference and risk ratio exceeded predefined equivalence margins.
The incidence of adverse events was similar between the groups, in both the neoadjuvant and adjuvant phases. In the neoadjuvant phase of the trial, 5% of ABP 980 patients and 6% of trastuzumab patients had an adverse event that led to dose delays, and 1% in each group had an adverse event that led to discontinuation of therapy.
In the adjuvant phase of the trial, 5% of ABP 980 patients had an adverse event that led to a dose delay, compared with 4% in the trastuzumab group and 5% of those who switched from trastuzumab to ABP 980. Two percent of each group had events that led to treatment discontinuation. Grade 3 or worse adverse events were also similar, and no differences were reported in the incidence of events of interest.
“Safety, efficacy, and clinical outcomes did not differ for the biosimilar ABP 980 and trastuzumab reference product in women with HER2-positive early breast cancer,” the authors concluded. “Similarities persisted in the neoadjuvant and adjuvant phases, and switching from trastuzumab to ABP 980 did not lead to any new or unexpected safety signals. Overall, our results add to the evidence from analytical, functional, and pharmacokinetic studies supporting the clinical similar of ABP 980 and trastuzumab.”