New frontiers in oncology: biosimilar monoclonal antibodies for the treatment of breast cancer

Abstract

Trastuzumab is a highly successful monoclonal antibody (mAb) that has been used primarily for the treatment of HER2-positive breast cancer. Because of its success and its impending patent expiry in Europe in 2014, a number of copy versions of trastuzumab have been developed and are currently undergoing a comparability exercise for marketing authorization. Although biosimilar products have been approved in Europe since 2006, including two biosimilar mAbs of infliximab approved in 2013, the use of mAbs such as trastuzumab in the cancer setting has raised a number of new concerns. The requirements for the approval of biosimilar mAbs published by the EMA will be discussed and examined in the context of trastuzumab biosimilars to highlight potential controversies.

Keywords:

• biosimilar
• biosimilar antibody
• breast cancer
• CT-P6
• Herceptin
• monoclonal antibody
• trastuzumab

Acknowledgements

Medical writing assistance by J Klem, C Goins, M Tanzola and TG Stoddert, all of prIME Oncology (Atlanta, GA, USA), is acknowledged.

Financial & competing interests disclosure

The author was funded by F. Hoffman-La Roche, Ltd. The author has received consulting fees from Roche, Genomic Health, Amgen, AstraZeneca, Celgene, Novartis and Sysmex. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Trastuzumab is a highly successful monoclonal antibody whose patent will expire in 2014, inciting the development of a number of trastuzumab biosimilar antibodies.

• Celltrion has produced a trastuzumab biosimilar candidate, CT-P6, that has completed Phase III testing and has been approved as a biosimilar product in Korea.

• Although biosimilar products have been approved in Europe since 2006, the unique characteristics of monoclonal antibodies, particularly in the cancer setting, have raised a number of concerns regarding the approval of biosimilar antibodies.

• Monoclonal antibodies are distinct from other biologic products because of their large size, structural complexity, susceptibility to post-translational modification resulting from minor manufacturing differences and multiple mechanisms of action.

• Three concerns with the interpretation and/or enforcement of current EMA guidelines on biosimilar antibodies are the choice of a sensitive and homogeneous population for trastuzumab biosimilar testing, selection of an appropriate clinical endpoint for these trials and the requirements for extrapolation of indications.

• The future integration of trastuzumab biosimilars into clinical practice will depend not only on the scientific rigor with which they are approved but also the alternatives to Herceptin^® therapy available.

• The concerns over the approval of trastuzumab biosimilars should be addressed before they become a reality in Europe.