272P - Subcutaneous injection of trastuzumab - analysis of administration time and injection site reactions

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer, Early Stage
Presenter Xavier Pivot
Authors X. Pivot1, V. Semiglazov2, S. Chen3, S.D. Moodley4, A. Manihkas5, M.A. Coccia-Portugal6, M. Johnston7, T. van der Horst8, A. Bouhlel8, C. Jackisch9
  • 1Service Oncologie Medicale, C.H.U. Jean Minjoz, FR-25030 - Besancon CEDEX/FR
  • 2Breast Cancer Department, N.N.Petrov Research Inst. of Oncology, RU-197758 - St. Petersburg/RU
  • 3Division Of Breast Surgery, Chang Gung Memorial Hospital, Taipei/TW
  • 4Department Of Oncology, Wits Oncology Donald Gordon Medical Centre, Johannesburg/ZA
  • 5., St Petersburg City Oncology Centre, St.Petersburg/RU
  • 6., Eastleigh Breast Cancer Care Centre, Pretoria/ZA
  • 7., Genentech Inc, South San Francisco/US
  • 8., F. Hoffman-La Roche Ltd, Basel/CH
  • 9Oncology, Klinikum Offenbach GmbH, D-63069 - Offenbach/DE

Abstract

Background

Intravenous (IV) trastuzumab (H) is the standard of care for HER2-positive breast cancer (BC). A subcutaneous (SC) formulation of H has been developed. H SC formulation contains recombinant human hyaluronidase, which transiently hydrolyzes hyaluronan to facilitate delivery of H to the circulation. The HannaH study (Jackisch, et al. EBCC 2012) demonstrated the non-inferiority of H SC (vs. H IV) in terms of pharmacokinetics and efficacy in patients with HER2-positive early BC. Safety observations for the two routes of administration were also similar.

Methods

H SC injection was via handheld syringe, and an injection time of about 5 minutes was recommended by the study protocol. The actual time taken was measured in the safety population at each administration. Injection site reactions (ISRs) associated with H SC were identified using a predefined basket of preferred terms from the medical dictionary for drug regulatory activities.

Results

Duration of SC injections was generally between 1–5 minutes, with an average duration of 3.3 minutes (Table 1) compared with 60–90 minutes taken for IV administration. A low incidence of ISRs were seen with SC injections (Table 1), with all but two cases (grade 2) being grade 1; every case was reversible.

Injection duration (minutes) Number of injections n (%) Incidence of ISRs n (%)
< 2 51 (1.1) 0 (0)
≥ 2 to < 3 2231 (49.2) 27 (1.2)
≥ 3 to < 4 961 (21.2) 15 (1.6)
≥ 4 to < 5 200 (4.4) 6 (3.0)
≥ 5 to < 6 1024 (22.6) 27 (2.6)
≥ 6 45 (1.0) 9 (20.0)
Missing 25 (0.5) 0 (0)
Total 4537 (100) 84 (1.9)

Summary of injection duration and ISRs (injection site pain) in the H SC arm of the HannaH study (safety population) (N = 297) Incidence of ISRs was highest for injection durations of >6 minutes with 6 pts reporting 9 ISRs over the course of their treatment. In 3 pts (6 ISRs) injection time was prolonged due to injection pain. The remaining three ISRs constituted transient tissue tenderness at injection site.

Conclusion

In the HannaH study, injection of H SC was generally well tolerated with a low incidence of ISRs (grades 1 and 2). These findings support the potential of H SC to provide improved convenience for patients compared to the existing IV formulation.

Disclosure

X. Pivot: X. Pivot has served as a consultant or advisor for Hoffmann-La Roche, Novartis, GlaxoSmithKline and has received honoraria from sanofi-aventis.

S.D. Moodley: SD Moodly has served as a member of an advisory board for La Roche Hoffman, sanofi-aventis, Britol Meyers Squibb, Nayer Schering, and has received corporate-sponsored research funding from sanfoi-aventis.

M. Johnston: M Johnston is an employee of Genentech, a member of the Roche Group.

T. van der Horst: T Horst is an employee of F. Hoffman-La Roche Inc.

A. Bouhlel: A Bouchel is an employee of F. Hoffmann-La Roche Inc.

C. Jackisch: C. Jackisch has served on advisory boards for Hoffmann-La Roche Inc.

All other authors have declared no conflicts of interest.