273P - Immunogenicity of trastuzumab intravenous and subcutaneous formulations in the phase III HANNAH study

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Breast Cancer, Early Stage
Cancer Immunology and Immunotherapy
Presenter Roberto Hegg
Authors R. Hegg1, T. Pienkowski2, S. Chen3, E. Staroslawska4, S. Falcon5, N. Kovalenko6, N. Al-Sakaff7, D. Heinzmann7, G. Kolaitis8, G. Ismael9
  • 1Oncology, Hospital Pérola Byington and FMUSP, Sao Paulo/BR
  • 2MSC Memorial Cancer Centre and Institute Maria Sklodowska-Curie, PL-02-781 - Warsaw/PL
  • 3., Changhua Christian Hospital, Taipei/TW
  • 4., St. John’s Cancer Center, Lublin/PL
  • 5Oncologia Medica, , Hospital Nacional Edgardo Rebagliati Martins, Lima/PE
  • 6., Stavropol Regional Clinical Oncology Dispensary, Stavropol/RU
  • 7., Roche, Basel/CH
  • 8., Roche, Nutley/US
  • 9Medical Oncology/hematology, Hospital Amaral Carvalho, Jau/BR

Abstract

Background

HannaH demonstrated non-inferiority of the fixed-dose subcutaneous (SC) formulation of trastuzumab (H) to the intravenous (IV) formulation, based on pharmacokinetics (Ctrough) and efficacy (pathological complete response [pCR]) (Jackisch et al, EBCC 2012). We report on efficacy and safety in relation to immunogenicity (anti-drug antibodies [ADAs]).

Methods

Blood samples for ADA testing were drawn at baseline (BL), then day 1 of cycles 2, 5 (pre-surgery), 13 and 18 (post-surgery) and at months 3, 6, 12, 18 and 24 following last H dose. Screening for ADAs to H and rHuPH20 was by bridging immunoassays. Positive (pos) samples were re-tested, with confirmed pos patients (pts) then tested for neutralizing antibodies (abs). Relationship between ADAs (against H and/or rHuPH20) with respect to, efficacy (pCR) and safety (infusion-related reactions, IRRs) was investigated.

Results

The median follow-up (FU) (including ADA testing) was ∼12.3 months. At BL, 5.9% of pts (17/290) in the IV arm and 4.2% of pts (12/287) in the SC arm were pos for ADAs to H. Post-BL (treatment and FU), 3.4% (10/295) and 6.8% (20/295) pts in IV and SC, respectively were pos for ADAs to H. One pt was confirmed pos twice (non-consecutive time points). At BL, 7.6% of pts (22/290) in the SC arm were pos for ADAs to rHuPH20. Post-BL, the rate was 11.5% (34/295). Titer ranges post-BL were similar to those observed pre-BL. One pt was pos for ADAs to both H and rHuPH20. No neutralizing ADAs to H or rHuPH20 were seen. The pCR rate did not differ significantly between Anti-H ab (AHA)-pos (30% [IV n = 10], 55% [SC n = 20]) and AHA-neg (36.5% [IV n = 10], 41.6% [SC n = 20]) pts. Anti-rHuPH20 status did not correlate with pCR rates (41.2% [pos n = 34] vs 41.7% [neg n = 254]) in the SC arm. In pts given H SC or H IV, occurrences of IRRs were similar in AHA-neg (46.3% [SC n = 255] 37.6% [IV n = 263]) and -pos (40% [SC n = 20] 25% [IV n = 10]) pts. The incidence of pts with an IRR was similar in both anti-rHuPH20 status groups (SC arm only; neg 44.5% [n = 254], pos 41.2% [n = 34]).

Conclusion

Using a highly sensitive assay, ADAs against both H (IV/SC) and rHuPH20 (SC only) were observed transiently and were of no relevance in terms of efficacy or safety. Immunogenicity monitoring in the study is ongoing.

Disclosure

T. Pienkowski: Dr Pienkowski has carried out research sponsored by F Hoffmann La Roche.

N. Al-Sakaff: I have an interest in relation of one or more organistations that could be perceived as a conflict of interest in the context of the subjuect of this abstract. Interest - other substantive relationship. Employee of F.Hoffman-La Roche Ltd.

D. Heinzmann: I have an interest in relation of one or more organistations that could be perceived as a conflict of interest in the context of the subjuect of this abstract. Other substantive relationship: Employee of F Hoffman-La Roche and stockholder.

G. Kolaitis: Dr Kolaitis is an employee and stockholder of F Hoffmann La Roche.

G. Ismael: I have an interest that could be perceived as a conflict of interest in the context of the subjuect of this abstract. Corporate sponsored research - Roche Other substantive relationships - honoraria for conferences (Roche).

All other authors have declared no conflicts of interest.