LAUSR

580 Background: SB3 is an approved biosimilar of reference trastuzumab (TRZ). At additional 2-year follow-up after completing neoadjuvant and adjuvant treatment, there was a difference in event-free survival (EFS), but no difference in overall survival (OS) between SB3 and TRZ. Upon monitoring quality attributes of TRZ, a marked downward shift in antibody-dependent cell-mediated cytotoxicity activities (ADCC) was observed in TRZ lots with expiry dates from Aug 2018 to Dec 2019. Some of the lots were used in the Phase III study. This is a post-hoc analysis of EFS and OS by ADCC status from a 3-year follow-up to investigate the difference in EFS between SB3 and TRZ. Methods: After completion of neoadjuvant and adjuvant therapy in patients with HER2 positive early breast cancer, patients from selected countries participated in a 5-year follow-up study (NCT02771795). Within the TRZ group, patients exposed to at least one shifted ADCC lot and those never exposed to shifted ADCC lot during neoadjuvant period were considered as “Exposed” and “Unexposed,” respectively. EFS and OS after 3-year follow-up was analyzed by ADCC status in the long-term follow-up set. Results: 367 patients (SB3, N = 186; TRZ, N = 181) were enrolled in the follow-up study. Within TRZ, 55 patients were Unexposed and 126 patients were Exposed. At a median follow-up duration of 40.8 months in SB3 and 40.5 months in TRZ, 3-year EFS rates were 92.5% in SB3, 94.5% in Unexposed, and 82.5% in Exposed and OS rates were 97.0%, 100%, and 90.6%, respectively. Exposed was associated with decreased EFS compared to Unexposed (HR 0.14, 95% CI 0.04-0.51, p= 0.003). There was a trend of decreased OS in Exposed compared to Unexposed, however, there was no significant difference (HR 0.14, 95% CI 0.02-1.15, p= 0.068). Between SB3 and Unexposed, no difference was observed in EFS (HR 1.06, 95% CI 0.33-3.44, p= 0.923), or OS (HR 0.54, 95% CI 0.05-5.44, p= 0.600). Conclusions: Within the TRZ group, Exposed showed significantly lower EFS compared to Unexposed, and a similar trend was observed in OS with no statistical significance. Between SB3 and Unexposed, no significant difference in EFS or OS was observed. Clinical trial information: NCT02771795.