Effect of ADCC Shift in Lots of Trastuzumab Could Change Its Biosimilarity to SB3

Downward shift in ADCC shift suggests reference drug and its biosimilar are not completely identical.

SB3 has been approved as a biosimilar — ie, nearly identical version — to the drug trastuzumab for the treatment of HER2 breast cancer, with a highly comparable event-free survival. However, in evaluating trastuzumab to develop SB3, researchers observed that there was a notable downward shift in antibody-dependent cell-mediated cytotoxicity activities (ADCC) in lots of trastuzumab with expiration dates from August 2018 to December 2019.¹

This shift presents the possibility that SB3 and trastuzumab may not be completely identical. A recent follow-up study presented at the 2018 San Antonio Breast Cancer Symposium evaluated the effect of this shift using ADCC status to determine event-free survival.²

Patients with HER2-positive early or locally advanced breast cancer who underwent surgery randomly received either SB3 or trastuzumab in a neoadjuvant setting concurrently with chemotherapy. Patients who were exposed to at least 1 lot of shifted trastuzumab were classified as exposed (126 patients); patients who were not, were classified as unexposed (55 patients).

At a median follow-up period of 30 months from the start of the study treatment, a significantly higher number of patients (10.3%) who were exposed to shifted lots of trastuzumab experienced events including disease recurrence, progression, or death compared with unexposed patients (3.6%). The 2-year event-free survival rate was 98.2% for unexposed patients, 96.7% for SB3 patients, and 92.5% for exposed patients.

“Although this study has a relatively short follow-up and has not been powered to evaluate the impact of ADCC on survival, these results suggest a possible correlation between ADCC and clinical efficacy,” wrote the authors. “Further long-term results will follow.”

References

1. Kim S, Song J, Park S, et al. Drifts in ADCC-related quality attributes of Herceptin®: impact on development of a trastuzumab biosimilar. MAbs. 2017;9(4):704-714.

2. 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. Poster presentation at: 2018 San Antonio Breast Cancer Symposium; December 4-8, 2018; San Antonio, TX. Abstract P6-17-09.