Please use this identifier to cite or link to this item: https://observatorio.fm.usp.br/handle/OPI/2930
Title: IMMUNOGENICITY OF TRASTUZUMAB INTRAVENOUS AND SUBCUTANEOUS FORMULATIONS IN THE PHASE III HANNAH STUDY
Authors: HEGG, R.PIENKOWSKI, T.CHEN, S.STAROSLAWSKA, E.FALCON, S.KOVALENKO, N.AL-SAKAFF, N.HEINZMANN, D.KOLAITIS, G.ISMAEL, G.
Citation: ANNALS OF ONCOLOGY, v.23, suppl.9, p.103-103, 2012
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.
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Comunicações em Eventos - FM/MOG
Departamento de Obstetrícia e Ginecologia - FM/MOG

Comunicações em Eventos - HC/ICHC
Instituto Central - HC/ICHC

Comunicações em Eventos - LIM/58
LIM/58 - Laboratório de Ginecologia Estrutural e Molecular


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