Fiche publication
Date publication
novembre 2014
Auteurs
Membres identifiés du Cancéropôle Est :
Pr PIVOT Xavier
Tous les auteurs :
Jackisch C, Kim SB, Semiglazov V, Melichar B, Pivot X, Hillenbach C, Stroyakovskiy D, Lum BL, Elliott R, Weber HA, Ismael G
Lien Pubmed
Résumé
BACKGROUND: HannaH (NCT00950300) was a phase III, randomized, international, open-label study that compared pharmacokinetics (PK), efficacy, and safety of two different trastuzumab formulations (subcutaneous [SC] and intravenous [IV]) in HER2-positive, operable, locally advanced, or inflammatory breast cancer in the neoadjuvant/adjuvant setting. The co-primary endpoints, to show non-inferiority of SC versus IV trastuzumab in terms of serum concentration (Ctrough) and pathologic complete response (pCR) were met; safety profiles were comparable at 12 months' median follow-up. Secondary endpoints included safety and tolerability, PK profile, immunogenicity, and event-free survival (EFS). We now report updated safety and efficacy data after a median follow-up of 20 months. PATIENTS AND METHODS: Patients (N=596) were treated with 8 cycles of neoadjuvant chemotherapy, administered concurrently with 3-weekly SC trastuzumab (fixed dose of 600 mg) or the standard weight-based IV method. Following surgery, patients continued trastuzumab treatment to complete 1 year of therapy. Updated analyses of PK, efficacy, safety, and immunogenicity data were performed. RESULTS: SC trastuzumab was generally well tolerated and the incidence of adverse events (AEs), including grade 3 or 4 AEs, between treatment groups was comparable. A slightly higher incidence of serious AEs (SAEs), mainly due to infections, was reported with SC treatment (64 [21.5%; 95% confidence interval (CI) 17.0%-26.7%] versus 42 [14.1%; 95% CI 10.4%-18.6%] in the IV group); however, the differences were small and often based on rare events, with no observable pattern across reported events. An early analysis of EFS showed rates of 95% in both groups 1 year post-randomization. Exploratory analyses did not reveal an association between toxicity and body weight or exposure. CONCLUSIONS: Overall, the safety profile of SC trastuzumab was consistent with the previously published data from HannaH and the known safety profile of IV trastuzumab. EFS rates were comparable between the IV and SC groups.
Référence
Ann Oncol. 2014 Nov 17. pii: mdu524.
