Neoadjuvant–adjuvant subcutaneous trastuzumab (Herceptin® SC; H SC) is non-inferior to intravenous H (H IV) in terms of pathological complete response (pCR) in the breast for HER2-positive early breast cancer (EBC) (Jackisch, Lancet Oncol 2012). pCR/total pCR is associated with improved event-free survival in this setting, and H SC and H IV have comparable safety profiles (Jackisch, Lancet Oncol 2012; ASCO 2015). UmbHER1, a Phase IIIB, open-label, multinational umbrella study aims to assess the safety and tolerability of H SC in a broader patient population, including those with EBC or metastatic BC (MBC) treated with or without chemotherapy (CT) or pertuzumab (PERJETA®). UmbHER1 is composed of five EBC and two MBC studies; we present pooled interim safety data from the five EBC studies.
The EBC UmbHER1 studies are: NCT01940497 (neoadjuvant–adjuvant H SC + CT; N = 228), NCT01926886 (neoadjuvant–adjuvant H IV + H SC; N = 102), NCT02194166 (adjuvant H IV + H SC; N = 90), NCT01964391 (neoadjuvant–adjuvant H SC ± CT; N = 174), NCT02040935 (adjuvant H SC; N = 125). In all studies, H SC was administered as a 600 mg fixed dose and given every 3 weeks until progression/unacceptable toxicity/withdrawal (18 cycles/1 year). The overall primary objective is safety and tolerability. Results are descriptive and include all treatment cycles (H SC, H IV and CT).
The EBC safety population comprises 719 patients. There were 8219 H SC cycles administered for EBC by data cut-off (27 November 2015). The overall adverse event (AE) profile in the EBC population is shown in the table. The most common grade 3–4 serious AE (SAE) was decreased ejection fraction (3 patients, all grade 3).
|Patients, n (%)||Overall EBC population N = 719|
|Grade 1||533 (74)|
|Grade 2||344 (48)|
|Grade 3||103 (14)|
|Grade 4||18 (3)|
|AE leading to discontinuation||33 (5)|
|Grade 2||18 (3)|
|Grade 3||24 (3)|
|Grade 4||13 (2)|
|Injection-site reaction||105 (15)|
|Grade 1||91 (13)|
|Grade 2||14 (2)|
|Grade 3||1 (|
No new safety signals were identified with H SC, administered with or without CT for HER2-positive EBC, in this broad UmbHER1 population.
Clinical trial identification
NCT01940497 NCT01926886 NCT02194166 NCT01964391 NCT02040935
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd
F. Hoffmann-La Roche Ltd
X. Pivot: Consultant with honorarium for Roche, Amgen, Novartis, Eisai, Pierre Fabre. C. Poole: Advisory boards for Roche, Astra Zeneca, Lilly, Novartis, Pfizer and Genomic Health (in the last 2 years); Corporate sponsored research: Roche, Astra Zeneca, AB Science, Aeterna Zentaris (in last 2 years).
M. Martín: Membership of an advisory board (AstraZeneca, Celgene, Lilly, Novartis). J. Gligorov: Consultancy: Roche-Genentech; Eisai; Honoraria: Teva; Novartis-GSK; GenomicHealth. C.H. Barrios: Eisai Bioepis Pfizer Novartis Amgen AZ BI GSK Roche Lilly Sanofi Taiho Mylan Merrimack Merck Abbvie Astellas Biomarin BMS Daiichi Sankyo Abraxis AB Asana Medivation Daiichi Sankyo Exelixis ImClone LEO Millennium. E. Vrdoljak: Membership of an advisory board (Roche, Pfizer, Novartis, AstraZeneca, BMS); Corporate-sponsored research (Roche, Pfizer). L. Gianni: Membership of an advisory board (Roche/GNE; Pfizer; Synthon; Synaffix; Novartis; Genomic Health; AstraZeneca; Onkaido; Unum; Celgene; Genenta; Tiziana); Other substantive relationships (1 Co-Patenting with Roche). Z. Machackova: Stock ownership (F. Hoffmann-La Roche); Other substantive relationships (employee of F. Hoffmann-La Roche). M. Truman: Stock ownership (Roche, GSK); Other substantive relationships (Consultant to Roche). G. Steger: Membership of an advisory board (AstraZeneca, Roche, Amgen, Novartis, Pfizer, Teva, Celgene). All other authors have declared no conflicts of interest.