PMID- 25403587
OWN - NLM
STAT- MEDLINE
DCOM- 20160224
LR  - 20220331
IS  - 1569-8041 (Electronic)
IS  - 0923-7534 (Linking)
VI  - 26
IP  - 2
DP  - 2015 Feb
TI  - Subcutaneous versus intravenous formulation of trastuzumab for HER2-positive 
      early breast cancer: updated results from the phase III HannaH study.
PG  - 320-5
LID - 10.1093/annonc/mdu524 [doi]
AB  - 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 (s.c.) and intravenous (i.v.)] 
      in HER2-positive, operable, locally advanced, or inflammatory breast cancer in 
      the neoadjuvant/adjuvant setting. The co-primary end points, to show 
      noninferiority of s.c. versus i.v. 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 end points 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 eight cycles 
      of neoadjuvant chemotherapy, administered concurrently with 3-weekly s.c. 
      trastuzumab (fixed dose of 600 mg) or the standard weight-based i.v. method. 
      Following surgery, patients continued trastuzumab treatment to complete 1 year of 
      therapy. Updated analyses of PK, efficacy, safety, and immunogenicity data were 
      carried out. RESULTS: s.c. 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 s.c. treatment 64 [21.5%; 95% confidence 
      interval (CI) 17.0%-26.7%] versus 42 (14.1%; 95% CI 10.4%-18.6%) in the i.v. 
      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 postrandomization. Exploratory analyses did 
      not reveal an association between toxicity and body weight or exposure. 
      CONCLUSIONS: Overall, the safety profile of s.c. trastuzumab was consistent with 
      the previously published data from HannaH and the known safety profile of i.v. 
      trastuzumab. EFS rates were comparable between the i.v. and s.c. groups. CLINICAL 
      TRIAL NUMBER: NCT00950300.
CI  - (c) The Author 2014. Published by Oxford University Press on behalf of the European 
      Society for Medical Oncology. All rights reserved. For permissions, please email: 
      journals.permissions@oup.com.
FAU - Jackisch, C
AU  - Jackisch C
AD  - Department of Obstetrics and Gynecology and Breast Cancer and Gynecology Cancer 
      Center, Sana Klinikum Offenbach GmbH, Offenbach, Germany 
      christian.jackisch@sana.de.
FAU - Kim, S-B
AU  - Kim SB
AD  - Department of Oncology, Asan Medical Center, University of Ulsan College of 
      Medicine, Seoul, Korea.
FAU - Semiglazov, V
AU  - Semiglazov V
AD  - Department of Surgery, NN Petrov Research Institute of Oncology, St Petersburg, 
      Russia.
FAU - Melichar, B
AU  - Melichar B
AD  - Department of Oncology, Palacky University Medical School and Teaching Hospital, 
      Olomouc, Czech Republic.
FAU - Pivot, X
AU  - Pivot X
AD  - Chemotherapy-Oncology, CHU Jean Minjoz, Besancon, France.
FAU - Hillenbach, C
AU  - Hillenbach C
AD  - Department of Biopharmaceuticals, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
FAU - Stroyakovskiy, D
AU  - Stroyakovskiy D
AD  - Chemotherapeutic Department, City Clinical Oncology Hospital 62, Moscow, Russia.
FAU - Lum, B L
AU  - Lum BL
AD  - Clinical Pharmacology.
FAU - Elliott, R
AU  - Elliott R
AD  - BioAnalytical Sciences, Genentech, South San Francisco, USA.
FAU - Weber, H A
AU  - Weber HA
AD  - Department of Biopharmaceuticals, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
FAU - Ismael, G
AU  - Ismael G
AD  - Hospital Amaral Carvalho, Jau, Brazil.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20141117
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - 0 (Antineoplastic Agents)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - P188ANX8CK (Trastuzumab)
SB  - IM
MH  - Adult
MH  - Antineoplastic Agents/*administration & dosage/adverse effects/pharmacokinetics
MH  - Breast Neoplasms/*drug therapy/genetics
MH  - Female
MH  - Humans
MH  - Infusions, Intravenous
MH  - Injections, Subcutaneous
MH  - Middle Aged
MH  - Receptor, ErbB-2/biosynthesis/genetics
MH  - Trastuzumab/*administration & dosage/adverse effects
OTO - NOTNLM
OT  - HER2/neu
OT  - breast cancer
OT  - chemotherapy
OT  - neoadjuvant
OT  - subcutaneous
OT  - trastuzumab
EDAT- 2014/11/19 06:00
MHDA- 2016/02/26 06:00
CRDT- 2014/11/19 06:00
PHST- 2014/11/19 06:00 [entrez]
PHST- 2014/11/19 06:00 [pubmed]
PHST- 2016/02/26 06:00 [medline]
AID - S0923-7534(19)31376-6 [pii]
AID - 10.1093/annonc/mdu524 [doi]
PST - ppublish
SO  - Ann Oncol. 2015 Feb;26(2):320-5. doi: 10.1093/annonc/mdu524. Epub 2014 Nov 17.