271P - Additional safety results of HANNAH: a phase III randomised, open-label, international study of the subcutaneous formulation of trastuzumab (h) in H...

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Anticancer agents
Breast Cancer
Therapy
Biological therapy
Presenter Christian Jackisch
Authors C. Jackisch1, M. Dank2, G. Frasci3, K. Park4, R. Lopez5, M. Johnston6, D. Heinzmann7, H. Weber7, G. Ismael8
  • 1Oncology, Klinikum Offenbach GmbH, D-63069 - Offenbach/DE
  • 2Semmelweis Egyetem, Radiológiai és Onkoterápiás Klinika, Budapest/HU
  • 3Division Of Medical Oncology A, National Tumor Institute, Naples/IT
  • 4Department Of Internal Medicine, Korea University Anam Hospital, Seoul/KR
  • 5Medical Oncology Department, National Oncology Institute, Panama/PA
  • 6., Genentech Inc, South San Francisco/US
  • 7Clinical Science, F. Hoffmann-La Roche Ltd, Basel/CH
  • 8Medical Oncology/hematology, Fundation Amaral CarvalhoHospital of Jau, BR-17210-080 - Jau/BR

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.