Neoadjuvant Breast Cancer Treatment as a Sensitive Setting for Trastuzumab Biosimilar Development and Extrapolation

Jackisch, Christian; Scappaticci, Frank A.; Heinzmann, Dominik; Bisordi, Fabio; Schreitmüller, Thomas; Minckwitz, Gϋnter von; Cortés, Javier

doi:10.2217/fon.14.187

Cited by 39 publications

(33 citation statements)

References 33 publications

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“…For example, in scientific conferences and in recent literature, it is discussed whether, for biosimilar mAbs for breast cancer, neoadjuvant treatment should be favored over the metastatic setting, or whether, for biosimilar rituximab, extrapolation from a nononcological indication (rheumatoid arthritis) to an oncological indication (lymphoma) should be allowed. 50,51 Although the latter appears to be challenging, extrapolation may be possible, provided that all active moieties of the antibody molecule are rigorously tested and compared, and their functions (eg, that are different in the various lymphoma indications of rituximab) are established to be the same. Generally, all biosimilar developments-irrespective of whether they use the model systems that are emerging in clinical literature-have been critically discussed with regulators within scientific advice procedures.…”

Section: Discussionmentioning

confidence: 99%

Biosimilars: the science of extrapolation

Weise

Kurki

Wolff-Holz

et al. 2014

Blood

274

275

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Despite the establishment of a specific approval pathway, the issuance of detailed scientific guidelines for the development of similar biological medicinal products (so-called “biosimilars”) and the approval of several biosimilars in the European Union, acceptance of biosimilars in the medical community continues to be low. This is especially true in therapeutic indications for which no specific clinical trials with the biosimilar have been performed and that have been licensed based on extrapolation of efficacy and safety data from other indications. This article addresses the concerns frequently raised in the medical community about the use of biosimilars in such extrapolated indications and explains the underlying scientific and regulatory decision making including some real-life examples from recently licensed biosimilars.

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Section: Discussionmentioning

confidence: 99%

Biosimilars: the science of extrapolation

Weise

Kurki

Wolff-Holz

et al. 2014

Blood

274

275

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“…Jackisch et al [13 ]presented in an evaluation of the sensitivity of endpoints for eBC and mBC in similarity studies of trastuzumab RP and biosimilars that the shorter-term endpoint of ORR for the measurement of equivalence led to a substantial difference in long-term PFS despite prior findings suggesting ORR being a surrogate for PFS in mBC. They found that at an equivalence margin of 10% for ORR was associated with a difference in PFS of 3.2 months.…”

Section: Clinical Developmentmentioning

confidence: 99%

Biosimilar Trastuzumab in Clinical Trials: Differences or Not?

Thill

2019

Breast Care

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In the last decade, cancer therapies have increasingly taken the form of combination treatments in which biologic agents play a crucial role. In breast cancer, the treatment strategy is adjusted to intrinsic subtypes such as human epidermal growth factor receptor-2(HER2)-positive. With the introduction of trastuzumab, a monoclonal antibody against HER2, survival has significantly improved in early and metastatic breast cancer. Trastuzumab's patent has now expired and biosimilars are moving into the market. Several clinical trials have led to the approval of 5 different biosimilar trastuzumabs. Results proved similarity between the proposed biosimilar and the reference product without significant differences in efficacy and safety, although follow-up has been short. However, the shorter drug development process with its goal of showing similarity rather than patient benefit uses surrogate endpoints such as pathologic complete response and overall response rate, not survival endpoints in terms of the ‘gold standard' in evaluating cancer therapies. The aim of this article is to give insight into how to plan and perform a clinical trial to prove equivalence between a biosimilar trastuzumab and its reference product and to elucidate the setup and outcome of published clinical trials.

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“…In the single-dose study, anti-drug antibodies (ADA) were identified by day 29 in all animals administered PF-05280586 or rituximab-EU, and they persisted through day 85, the last day they were tested for. In the repeat-dose study, ADA were detected on day 121 in 50% of Contrary to the initial biosimilars used in supportive care, trastuzumab is an anticancer drug, a specific targeted agent and thus it appears that the neoadjuvant setting may be the right choice to compare a trastuzumab biosimilar with the originator to assess efficacy and safety [Jackisch et al 2015]. Several trastuzumab biosimilars are either ready to be commercialized or are in clinical development [Hurst et al 2014].…”

Section: Pf-05280586mentioning

confidence: 99%

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

Gascón

2015

Therapeutic Advances in Hematology

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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.

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Neoadjuvant Breast Cancer Treatment as a Sensitive Setting for Trastuzumab Biosimilar Development and Extrapolation

Abstract: Treatment of patients with neoadjuvant breast cancer represents a sensitive setting for establishing biosimilarity of efficacy and immunogenicity. tpCR is a sensitive end point in this setting to establish biosimilarity between a biosimilar candidate and its reference product.

Cited by 39 publications

References 33 publications

Biosimilars: the science of extrapolation

Biosimilars: the science of extrapolation

Biosimilar Trastuzumab in Clinical Trials: Differences or Not?

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

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