Background: SB3 has been approved by the European Commission as a biosimilar of reference trastuzumab (TRZ). Equivalent breast pathologic complete response (bpCR) rate and comparable event-free survival (EFS) and overall survival between SB3 and TRZ have been reported.1-3 Upon monitoring quality attributes of TRZ for the development of SB3, 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 2019.4 Some of these lots were used in this study. The objective of this report is to evaluate event-free survival by ADCC status from an additional one-year follow-up study.

Methods: Patients with HER2 positive early or locally advanced breast cancer were randomly assigned to receive SB3 or TRZ in neoadjuvant setting concurrently with chemotherapy. Patients then underwent surgery followed by adjuvant SB3 or TRZ. After completion of therapy, patients from selected countries participated in a long-term follow-up study. In TRZ, patients exposed to at least one shifted ADCC lot and those not exposed to shifted ADCC lot during neoadjuvant period were considered as “Exposed” and “Unexposed,” respectively. EFS was defined as the time from the date of randomization to the date when the first event occurred. An event was defined as disease recurrence or progression (local, regional, distant or contralateral) or death due to any cause. EFS after additional one-year follow-up was analyzed by ADCC status in the long-term follow-up set (LFS).

Results: A total of 367 patients (SB3, N=186; TRZ, N=181) were included in the LFS. Within TRZ, 55 patients were Unexposed and 126 patients were Exposed. At a median follow-up duration of 30.1 months in SB3 and 30.2 months in TRZ from initiation of study treatment, 4.8% patients in SB3, 3.6% in Unexposed and 10.3% in Exposed experienced events. 4.3% patients in SB3, 1.8% in Unexposed and 9.5% in Exposed experienced recurrence after surgery (Table). Two-year EFS rate was 96.7% in SB3, 98.2% in Unexposed and 92.5% in Exposed.

Conclusion: A significantly higher proportion of patients experienced events in Exposed compared to Unexposed (HR 0.07, 95% CI 0.01-0.58, p-value=0.0137). No significant difference in EFS was found between SB3 and Unexposed. 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. Further long-term results will follow.

Summary of Event-free Survival (LFS)

    TRZ EFS Hazard ratio (95% CI), p-value 
  SB3 N=186 All N=181 Unexposed N=55 Exposed N=126 SB3 vs TRZ All SB3 vs TRZ Unexposed TRZ Unexposed vs TRZ Exposed 
Patients with event, n (%) 9 (4.8%) 15 (8.3%) 2 (3.6%) 13 (10.3%) 0.49 (0.21, 1.14) p=0.0975 1.19 (0.23, 6.18) p=0.8376 0.07 (0.01, 0.58) p=0.0137 
Recurrence after surgery 8 (4.3%) 13 (7.2%) 1 (1.8%) 12 (9.5%)       
Progression before surgery 1 (0.5%) 1 (0.6%) 1 (1.8%) 0 (0.0%)       
Death 0 (0.0%) 1 (0.6%) 0 (0.0%) 1 (0.8%)       
    TRZ EFS Hazard ratio (95% CI), p-value 
  SB3 N=186 All N=181 Unexposed N=55 Exposed N=126 SB3 vs TRZ All SB3 vs TRZ Unexposed TRZ Unexposed vs TRZ Exposed 
Patients with event, n (%) 9 (4.8%) 15 (8.3%) 2 (3.6%) 13 (10.3%) 0.49 (0.21, 1.14) p=0.0975 1.19 (0.23, 6.18) p=0.8376 0.07 (0.01, 0.58) p=0.0137 
Recurrence after surgery 8 (4.3%) 13 (7.2%) 1 (1.8%) 12 (9.5%)       
Progression before surgery 1 (0.5%) 1 (0.6%) 1 (1.8%) 0 (0.0%)       
Death 0 (0.0%) 1 (0.6%) 0 (0.0%) 1 (0.8%)       

Reference:

1. Pivot X et al. J Clin Oncol. 2018; 36:968-74

2. Pivot X et al. Eur J Cancer. 2018; 93:19-27

3. Pivot X et al. J Clin Oncol. 2018; 36 (suppl; abstr e12631)

4. Kim S et al. MAbs. 2017; 9:704-14

Citation Format: Pegram MD, Pivot X, Cortes J, Curigliano G, Yoon Y, Lim J, Song S, Hong E. 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 [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-17-09.