Abstract PD3-11: Efficacy and safety of subcutaneous or intravenous trastuzumab in patients with HER2-positive early breast cancer after 5 years' treatment-free follow-up: Final analysis from the phase III, open-label, randomized HannaH study

Background HannaH (NCT00950300) compared subcutaneous and intravenous trastuzumab (H SC and H IV) as neoadjuvant–adjuvant therapy for HER2-positive breast cancer. The co-primary endpoints of pathological complete response (pCR) and serum trough concentration at predose cycle 8 demonstrated noninferiority between H SC and H IV. Efficacy analyses of event-free survival (EFS) and overall survival (OS) at a median follow-up of 40 months supported this noninferiority. Safety analyses also confirmed the consistency of the safety profile across both arms. In this final follow-up analysis, we report the long-term efficacy and safety outcomes at 5 years of treatment-free follow-up (TFFU; 6 years in total). The correlation between total pCR (tpCR; absence of invasive neoplastic cells in ipsilateral nodes and the breast) and EFS was also explored. Methods Enrolled patients (n=596; pts) were randomized to receive 4 cycles of docetaxel, then 4 cycles of 5-fluorouracil/epirubicin/cyclophosphamide concurrently with 3-weekly fixed-dose 600mg H SC or H IV (loading: 8mg/kg; maintenance: 6mg/kg) in the neoadjuvant setting. Post-surgery, pts received an additional 10 cycles of H SC or H IV in the adjuvant setting to complete 1 year of anti-HER2 therapy. EFS (time from randomization to local, regional, or distant recurrence, contralateral breast cancer, or death) and OS were calculated using the Kaplan-Meier method. Adverse events (AEs) and serious AEs were recorded and graded per standard criteria. Results In total, 297 pts were randomized to the H SC arm and 299 to the H IV arm; 294 and 297 pts were included in the respective efficacy analysis populations. Median duration of follow-up (including TFFU) was 70.8 and 71.4 months in the H SC and H IV arms, respectively. EFS and OS were similar across both study arms (Table 1). Pts who achieved tpCR had longer EFS and OS vs. those who did not (Table 1). Cardiac AE incidence was low and consistent across study arms (Table 2). Conclusion Long-term efficacy EFS and OS results confirmed the noninferiority of H SC compared with H IV, as demonstrated by pCR and pharmacokinetic endpoints. tpCR was associated with longer EFS and OS. The overall safety profile of H SC was consistent with that of H IV. Citation Format: Jackisch C, Stroyakovskiy D, Pivot X, Ahn J-S, Melichar B, Chen S-C, Meyenberg C, Al-Sakaff N, Heinzmann D, Hegg R. Efficacy and safety of subcutaneous or intravenous trastuzumab in patients with HER2-positive early breast cancer after 5 years9 treatment-free follow-up: Final analysis from the phase III, open-label, randomized HannaH study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD3-11.