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).

Table 1

  H SC H IV Hazard Ratio (95% CI) 
6-year EFS, % (95% CI) n=294 n=297   
Overall 65 (59;70) 65 (60;71) 0.98 (0.74;1.29) 
tpCR status* tpCR n=102 n=90   
    80 (73;88) 83 (75;91)   
  no tpCR n=158 n=173   
    57 (49;65) 61 (54;69)   
6-year OS, % (95% CI) n=294 n=297   
Overall 84 (79;88) 84 (79;88) 0.94 (0.61;1.45) 
  H SC H IV Hazard Ratio (95% CI) 
6-year EFS, % (95% CI) n=294 n=297   
Overall 65 (59;70) 65 (60;71) 0.98 (0.74;1.29) 
tpCR status* tpCR n=102 n=90   
    80 (73;88) 83 (75;91)   
  no tpCR n=158 n=173   
    57 (49;65) 61 (54;69)   
6-year OS, % (95% CI) n=294 n=297   
Overall 84 (79;88) 84 (79;88) 0.94 (0.61;1.45) 

* Efficacy per protocol population

Cardiac AE incidence was low and consistent across study arms (Table 2).

Table 2

Pts, n (%) H SC (n=297) H IV (n=298) 
Any AE 290 (98) 282 (95) 
≥ Grade 3 AE 158 (53) 160 (54) 
Serious AE 65 (22) 45 (15) 
Cardiac AE 44 (15) 42 (14) 
LVEF decline (≥10%-points from baseline to <50%) 11 (3.8) 12 (4.2) 
Pts, n (%) H SC (n=297) H IV (n=298) 
Any AE 290 (98) 282 (95) 
≥ Grade 3 AE 158 (53) 160 (54) 
Serious AE 65 (22) 45 (15) 
Cardiac AE 44 (15) 42 (14) 
LVEF decline (≥10%-points from baseline to <50%) 11 (3.8) 12 (4.2) 

LVEF, left ventricular ejection fraction

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 years' 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.