A related commentary discusses this research. The study has some strengths and weaknesses and raises a curious regulatory issue. To begin with the weaknesses, only 696 of 725 randomised patients were evaluable for pathological complete response after surgery. No data about the outcomes, characteristics, or allocated treatment of the patients who did not reach surgery were provided. These lost patients should have been included in the intention-to-treat analysis and their responses classified when possible (eg, those who did not reach surgery due to progressive disease should have been classified as non-pathological complete response). The effect of these few patients on the overall results is unknown, although it is possibly small.
Among the strengths of the study were that the trial was done in a sensitive population (ie, a population in which differences in safety, immunogenicity, and efficacy could be attributed to the biosimilar or reference drug rather than patient-related or disease-related factors)
In theory, a proposed biosimilar product cannot be superior to its reference product. To show similarity in antitumor activity, therefore, an equivalence design aimed at confirming neither inferiority or superiority is usually selected. Such a design was used in the study trial, but the results mean that non-superiority of ABP 980 over trastuzumab could not be formally ruled out. Nevertheless, the Committee for Medicinal Products for Human Use of the European Medicines Agency has decided that ABP 980 fulfils the requirements for being approved as a trastuzumab biosimilar. Perhaps the results of the central pathological analysis, which comply with the predefined equivalence margins, have played a part in this decision. What might have happened if the central and local analyses had both been unable to rule out superiority of ABP 980 over trastuzumab is unclear.
The study trial was well performed and shows that ABP 980 is not inferior to trastuzumab. It also, however, lays the grounds for reflection about the complexities of the anticancer biosimilar regulatory framework.