The evolving role of biosimilars in haematology-oncology: a practical perspective.

The loss of patents covering many biopharmaceutical/biological agents in the mid 1990s led to the introduction of a new generation of drugs: biosimilars. These new agents, produced by living cells just as the originator drugs, are chemically highly similar to endogenous human proteins; characterized by three-dimensionally complex, high molecular weight compounds. Among the first biosimilars used in haematology-oncology were erythropoietin and granulocyte colony-stimulating factor. After five years of use in clinical practice, the efficacy and safety profile of biosimilars approved by the European Medicines Agency is excellent. Over the next year or two, biosimilar monoclonal antibodies (MoAbs) will become available; the first will be rituximab and trastuzumab. Not only are MoAbs more complex in terms of molecular weight and number of amino acids than the first biosimilars, but they are also anticancer drugs, not merely supportive treatments like their predecessors. This opens up important questions. How are regulatory agencies to assess their clinical efficacy, immunogenicity and safety? Is the neoadjuvant clinical setting the best to evaluate them? What will regulatory agencies decide in terms of switching an originator molecule for a biosimilar or extrapolating efficacy results from one pathology to another? Once biosimilars of rituximab and trastuzumab are approved, several challenging issues will need to be addressed such as how to maintain appropriate pharmacovigilance, how to extrapolate across indications, and issues concerning automatic substitution. There is currently no consensus in any of these areas. This review addresses all these issues: new challenges that the oncology community will face in the near future.