Between patients treated with the biosimilar and those treated with the reference product who were not exposed to lots of Herceptin with lower antibody-dependent cell-mediated cytotoxicity, no difference was observed in event-free survival (EFS) or overall survival (OS).
Samsung Bioepis’ SB3 (Ontruzant) has been approved in the United States and European Union as a biosimilar of the brand-name trastuzumab, Herceptin. Approval relied in part on a phase 3 study comparing the biosimilar with the reference in women with HER2-positive early or locally advanced breast cancer in the neoadjuvant setting.
Notably, some of the lots of the reference trastuzumab that were used in the study—with expiry dates from August 2018 to December 2019—had been impacted by a product shift that resulted in changes to antibody-dependent cell-mediated cytotoxicity (ADCC).
At the time, ADCC was not fully understood to be key to the efficacy of trastuzumab. However, in results that were presented in late 2018 at the San Antonio Breast Cancer Symposium, the importance of this quality attribute and its impact on event-free survival (EFS) came into clearer focus.
According the 2018 study data, 126 patients had been exposed to at least 1 lot of reference trastuzumab that had lower ADCC activity.2 Another 55 patients given the reference therapy were not exposed to these lots. After 30.1 months of treatment with the biosimilar—which was given to 186 patients—and 30.2 months of treatment with the reference, there was no statistically significant difference in EFS between the biosimilar arm (96.7%) and the patients who were not exposed to the lower-ADCC activity lots of the reference (98.2%). However, in the patients exposed to the lower-ADCC activity reference, 2-year EFS was lower (92.5%).
This week, during the 2019 American Society of Clinical Oncology Annual Meeting, researchers presented the 3-year results of an evaluation of survival by ADCC status.2
At a median follow-up of 40.8 months in the biosimilar arm and 40.5 months in the reference arm, EFS rates were 92.5% in the biosimilar arm, 94.5% among patients treated with the reference who were not exposed to the lower-ADCC activity lots, and 82.5% among patients who were exposed. Overall survival (OS) rates were 97.0%, 100%, and 90.6% in the 3 groups, respectively.
Among those treated with the reference, exposure was associated with decreased EFS compared with no exposure (hazard ratio [HR], 0.14; 95% CI, 0.04-0.51, P = .003). There was a trend of decreased OS in the exposed group compared with the unexposed group, but no significant difference emerged (HR, 0.14; 95% CI, 0.02-1.15, P = .068).
Between patients treated with the biosimilar and those treated with the reference product who were not exposed to the lower-ADCC lots, no difference was observed in EFS (HR, 1.06; 95% CI, 0.33-3.44, P = .923) or OS (HR, 0.54; 95% CI, 0.05-5.44, P = .600).
The investigators concluded that patients exposed to the lower-ADCC lots of the reference had significantly lower EFS than those who were not exposed, while the biosimilar-treated patients and those unexposed to the affected lots had no significant differences in EFS or OS.
1. Pegram MD, Pivot X, Cortes J, et al. Event-free survival by ADCC status from a follow-up study comparing SB3 (trastuzumab biosimilar) with reference trastuzumab for HER2 positive breast cancer in neoadjuvant setting. Presented at: 2018 San Antonio Breast Cancer Symposium, December 4-8, 2018; San Antonio, Texas. Abstract P6-17-09.
2. Pivot X, Pegram MD, Cortes J, et al. Evaluation of survival by ADCC status: Subgroup analysis of SB3 (Trastuzumab Biosimilar) and reference trastuzumab in patients with HER2-positive early breast cancer at three-year follow-up. Presented at: the American Society of Clinical Oncology Annual Meeting 2019; May 31-June 4, 2019; Chicago, Illinois. Abstract 580.