Subcutaneous versus intravenous formulation of trastuzumab for HER2-positive early breast cancer: updated results from the phase III HannaH study.
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.


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.


BACKGROUND
NCT00950300.
Department of Obstetrics and Gynecology and Breast Cancer and Gynecology Cancer Center, Sana Klinikum Offenbach GmbH, Offenbach, Germany christian.jackisch@sana.de.
C
C
Jackisch
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
S-B
SB
Kim
Department of Surgery, NN Petrov Research Institute of Oncology, St Petersburg, Russia.
V
V
Semiglazov
Department of Oncology, Palacký University Medical School and Teaching Hospital, Olomouc, Czech Republic.
B
B
Melichar
Chemotherapy-Oncology, CHU Jean Minjoz, Besançon, France.
X
X
Pivot
Department of Biopharmaceuticals, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
C
C
Hillenbach
Chemotherapeutic Department, City Clinical Oncology Hospital 62, Moscow, Russia.
D
D
Stroyakovskiy
Clinical Pharmacology.
B L
BL
Lum
BioAnalytical Sciences, Genentech, South San Francisco, USA.
R
R
Elliott
Department of Biopharmaceuticals, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
H A
HA
Weber
Hospital Amaral Carvalho, Jaú, Brazil.
G
G
Ismael
D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D000068878:Trastuzumab / Q000008:administration & dosage* / Q000009:adverse effects
D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab
HER2/neu; breast cancer; chemotherapy; neoadjuvant; subcutaneous; trastuzumab