Additional Safety Results of Hannah: A Phase III Randomised, Open-Label, International Study of the Subcutaneous Formulation of Trastuzumab (H) in HER2-Positive Early Breast Cancer Patients

ABSTRACT Background HannaH demonstrated non-inferiority of the fixed-dose subcutaneous (SC) formulation of H compared with the intravenous (IV) formulation, based on co-primary endpoints of pharmacokinetics (Ctrough) and efficacy (pCR) (Jackisch et al, EBCC 2012). Methods Pts with HER2-positive, operable, locally advanced or inflammatory BC were randomised to receive 8 cycles of chemotherapy (4x docetaxel 75 mg/m2 followed by 4x FEC 600/75/600 mg/m2) concurrently with 3-wkly H, either SC (600 mg/5 mL) or IV (8 mg/kg to 6 mg/kg). After surgery, pts continued H-SC or IV to complete 1 year of treatment. Safety has been monitored until 24 mths after last dose of H, including cardiac monitoring. Results Safety data from 298 (IV) /297 (SC) HannaH pts were analysed. At a median F/U of 12.3 months, 116 pts had completed adjuvant treatment and received a median of 17.5 (IV) and 17.0 (SC) H cycles. Pt characteristics were balanced at baseline. Overall, safety was comparable between arms. Most common AEs (>25% in either arm) were alopecia, nausea, neutropenia, diarrhoea, asthenia, and fatigue, with similar incidence in the two arms. Incidence of severe AEs (≥ grade 3) was comparable between arms (both 52%); the most common of which were haematologic (36.9 [IV] v 35.4% [SC]), GI (6.4 v 5.7%) and infections (5.0 v 6.7%). Serious AEs (SAEs) were reported in 12.4% (IV) v 20.9% (SC) of pts. The imbalance was largely driven by increased reporting of SAEs in the “infections” disease category in the SC v the IV arm (38.7 v 35.1%). Multiple logistic regression analyses did not reveal interactions between route of H treatment, body weight, and exposure (AUC) for SAEs or grade 3–5 AEs. AEs led to the withdrawal of 2.3% (IV) and 5.7% (SC) pts, with a contribution from cardiac AEs (3.0% [SC] v 1.3% [(IV]). Grade 1/2 AEs were reasons for withdrawal in 43% (IV) v 61% (SC) of pts. Grade 1/2 cardiac AEs led to withdrawal in 1.0% (IV) v 2.0% (SC) of pts. Incidence of cardiac AEs was similar in both arms: 12.1% % (IV) v 11.4% (SC). Conclusions The safety profile of H-SC was comparable to that of H-IV. Detailed analyses of observed imbalances in SAEs and withdrawals will be provided. Disclosure C. Jackisch: I have participated in an advisory board for Roche. M. Johnston: I am currently an employee of Genentech Inc. D. Heinzmann: I am currently an employee of F. Hoffmann-La Roche. H. Weber: I am currently an employee of F. Hoffmann-La Roche. G. Ismael: I declare that my institute has received research funding from Roche and honoraria for attendance at conferences. All other authors have declared no conflicts of interest.