An open-label, multinational, multicentre, phase IIIB umbrella study of subcutaneous trastuzumab with or without chemotherapy or pertuzumab in patients with HER2-positive early or metastatic breast cancer (UmbHER1): Interim safety results from early breast cancer studies

Date

10 Oct 2016

Session

Poster display

Presenters

Xavier Pivot

Citation

Annals of Oncology (2016) 27 (6): 43-67. 10.1093/annonc/mdw364

Authors

X. Pivot1, C. Poole2, M. Martín3, J. Gligorov4, C.H. Barrios5, E. Vrdoljak6, L. Gianni7, A.J. Ten Tije8, Z. Machackova9, M. Truman10, G. Steger11

Author affiliations

  • 1 Chemotherapy – Oncology, CHU Jean Minjoz, 25030 - Besançon/FR
  • 2 Arden Cancer Centre, University Hospital Coventry and Warwickshire, Coventry/GB
  • 3 Department Of Medical Oncology, Instituto de Investigación Sanitaria Gregorio Marañón, Universidad Complutense de Madrid, Madrid/ES
  • 4 Medical Oncology Department, APHP-Tenon; IUC-UPMC; Sorbonne University, Paris/FR
  • 5 Department Of Medicine, Pontifical Catholic University of Rio Grande do Sul School of Medicine, Porto Alegre/BR
  • 6 Clinic For Oncology And Radiotherapy, University Hospital Split, Split/HR
  • 7 Medical Oncology, San Raffaele IRCCS, Milan/IT
  • 8 Department Of Medical Oncology, Amphia Ziekenhuis, Breda/NL
  • 9 Global Product Development/medical Affairs Oncology (pdmao), F. Hoffmann-La Roche Ltd, Basel/CH
  • 10 Pdma Operations (biometrics), F. Hoffmann-La Roche Ltd, Dee Why/AU
  • 11 Department Of Internal Medicine, Medical University of Vienna, Vienna/AT
More

Resources

Background

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.

Methods

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).

Results

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
AE 588 (82)
Grade 1 533 (74)
Grade 2 344 (48)
Grade 3 103 (14)
Grade 4 18 (3)
AE leading to discontinuation 33 (5)
SAE 52 (7)
Grade 1 0
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 (

Conclusions

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

Funding

F. Hoffmann-La Roche Ltd

Disclosure

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.

Resources from the same session

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and can only be disabled by changing your browser preferences.