C
ancer care continually places huge financial demands on our healthcare systems, mainly owing to a growing population, people living longer and the increase cost of cancer drugs (Aapro, 2013; Hirsch and Lyman, 2013).All these factors translate to cancer care being one of the most costly specialties requiring funding (Henry and Taylor, 2014). Since 2014, a number of manufacturers have lost their patent for manufacturing cancer drugs (Aapro, 2013). They also lost data exclusivity, allowing other manufacturers to develop biosimilars for use in clinical practice (Aapro, 2013; Abrabam, 2013). This accounts for the influx of biosimilars onto the market, which are now seen as playing a key part in the treatment of cancer, and were initially only seen in the supportive care setting (Rak Tkaczuk and Jacobs, 2014). Biosimilar drugs are developed as a result of another manufacturer not being able to replicate the drug exactly (Abraham, 2013). The development process is relatively easy for small-molecule drugs, but much harder when considering the large molecules that make up biologics (Rak Tkaczuk and Jacobs, 2014). The rationale behind biosimilars is to develop a drug that exhibits a similar chemical composition profile to the patented drug, and manufacturers must demonstrate similarities in activity and pharmacokinetics i.e. mode of action, mechanism of absorption and distribution, along with metabolism and excretion. The manufacturer of the off-patent drug must demonstrate bioequivalence between the biosimilar and the previously patented drug (Mellstedt, 2013). This process enables the existing efficacy and safety data to be used as supportive evidence during the approval process (Rak Tkaczuk and Jacobs, 2014). Some feel there is a need for more comparative clinical trials to be undertaken, which will either support the economic evidence for biosimilars or not (Hirsch and Lyman, 2013). In 2011, the National Comprehensive Cancer Network (NCCN) undertook a survey of health professionals attending its annual conference to determine knowledge and concerns regarding biosimilars and their use in clinical practice. The results demonstrated that around half the health professionals surveyed were not at all, or only slightly, familiar with the development process of biosimilars.Those with knowledge of biosimilars also indicated a high level of interest in using biosimilars once they were approved. That same year, the NCCN formed the Biosimilars
S28
Work Group, which took a multiprofessional approach and produced a consensus statement outlining recommendations and support for the implementation of biosimilars into clinical practice (Zelenetz et al, 2011). Patented drugs remain identical to the original product in terms of dose, strength, route of administration and safety profile (Mellstedt, 2013). The same cannot be said of biosimilars (Aapro, 2013); although they are referred to as highly similar, they are not identical (Abraham, 2013). This means they will have the same mechanism of action and molecular similarities (Henry and Taylor, 2014), but there may be possible changes at a cellular level between batches of the same drug (Aapro, 2013) as a result of the manufacturing process (Mellstedt, 2013). Even with the same manufacturing process, these changes may occur over time, which may alter the nature and activity of the drug (Hirsch and Lyman, 2013). Companies are therefore required to demonstrate that this process does not result in any meaningful changes to either the efficacy or safety of the drug produced (Rak Tkaczuk and Jacobs, 2014). The main safety concern raised by prescribers regarding the use of biosimilars is immunogenicity owing to the immune responses caused by the possible structural changes during the manufacturing process (Rak Tkaczuk and Jacobs, 2014). These changes, no matter how small, may lead to hypersensitivity reactions not previously seen with the use of biologics (Abraham, 2013). Another concern is around interchangeability, where two products can be exchanged without affecting the health outcomes (Rak Tkaczuk and Jacobs, 2014) as potential switching of a drug part way through a patient’s planned treatment may result in a different side effects profile (Hirsch and Lyman, 2013; Mellstedt, 2013). Prescribers are concerned that this may happen without their knowledge i.e. automatic substitution at the dispensing level (Abraham, 2013; Gascón et al, 2013). These concerns are being address, for example by the European Organisation for Research and Treatment of Cancer (EORTC) granulocyte stimulating factor G-CSF clinical guidelines, which state that automatic substitution should not happen without the prescribers consent (Aapro et al, 2011). In the UK, these concerns are considered by a panel of experts on behalf of the National Institute for Health and Care Excellence (NICE).
The panel is responsible for undertaking a systematic review of the evidence relating to a drug’s potential benefit and possible safety concerns before recommending it be funded by the NHS. These reviews apply equally to both original biologic and biosimilars drugs (Henry and Taylor, 2014).The Medicines and Healthcare products Regulatory Agency (MHRA) has also issued guidance to ensure biosimilars are monitored and tracked in accordance with the European Union pharmacovigilance legislation (Generics and Biosimilars Initiative online, 2012). Currently biosimilars used in clinical practice are mainly in the supportive setting i.e. Binocrit® (biosimilars epoetin alpha) and Zarzio® (biosimilar filgrastim) (Aapro, 2013). Abraham (2013) explained the connection between the launch of a biosimilars of filgrastim and the reduction in spending per patient, together with an increase in accessing the drug to support patients receiving chemotherapy who are at risk of neutropenia. This change in prescribing practice has also shown the drug is used earlier in the patient’s management (Henry and Taylor, 2014). Gascón et al (2013) outlined the process that resulted in Zarzio gaining approval for use in clinical practice. This process compared the quality of the product with Neupogen® (the originator) and demonstrated that the product in terms of physiochemical and biological comparability was favourable, as was its efficacy. The use of Zarzio in Europe has shown that a biosimilar drug can meet regulatory requirements and, importantly, has shown favourable efficacy and safety when compared with the originator (Rak Tkaczuk and Jacobs, 2014). Current evidence suggests that biosimilars offer both a safe and effective alternative to original drugs (Gascón et al, 2013) with added reassurance around the development, manufacture and licensing, which appear to be even more stringent than those for traditional drugs (Aapro, 2013). Many concerns may be alleviated through adequate pharmacovigiliance to truly monitor the patient’s experience of receiving biosimilars. However, this will take time and is reliant on good reporting and analysis of acquired data (Hirsh and Lyman, 2013). Traceability of biosimilars, in terms giving individual product names to biosimilars, will also assist in addressing some concerns and support pharmacovigiance (Gascón et al, 2013). The increased use of biosimilars may be seen as a possible cost saving in the treatment
© 2015 MA Healthcare Ltd
The rise of biosimilars in cancer care
British Journal of Nursing, 2015 (Oncology Supplement), Vol 24, No 4
British Journal of Nursing. Downloaded from magonlinelibrary.com by 193.061.135.112 on November 24, 2015. For personal use only. No other uses without permission. . All rights reserved.
COMMENT of cancer, offering greater access to treatments and providing the option for treatments to be introduced earlier (Henry and Taylor, 2014; Rak Tkaczuk and Jacobs, 2014). One option is that the money saved by the introduction of biosimilars in the supportive setting may be reinvested in the use of treatments to manage the cancer i.e. monoclonal antibodies (Abraham, 2013; Aapro, 2013), which are currently some of the most expensive systemic anti-cancer treatments. As a result of the number of drugs losing their patent, the emphasis is now on manufacturing biosimilars to replace other drugs i.e. monoclonal antibodies and not just supportive treatments (Aapro, 2013). The changes to the market in terms of offpatent drugs and the development of biosimilars may encourage manufacturers to review their pricing as a way of ensuring their products remain competitive (Hirsch and Lyman, 2013). The pricing of drugs was discussed during the recent review of the Cancer Drug Fund (CDF) in England announced in January 2015, which saw the removal of some drugs. This decision to remove certain drugs was based on newer evidence relating to their properties and their cost-effectiveness, yet some manufacturers felt the costs could not be lowered owing to the expense of progressing a drug from the laboratory to the clinical setting (NHS England,
2015). Other incentives to use biosimilars are when the care is delivered as a ‘bundle’ and the provider may wish to use a slightly cheaper drug with equal efficacy (Hirsch and Lyman, 2013), resulting in a cost saving for the provider. We need to know when a patient is receiving a biosimilar drug, and have an understanding of the drug mechanisms and potential differences in the side effect profiles. We need this knowledge in order to act as advocates for patients, offering them continued support and advice regarding their current or future care. Biosimilars have been used in supportive care, but are now moving into the systemic anticancer treatments option; there is a need for us to keep abreast of changes, especially as there may be different biosimilars for different tumour groups, when previously there would have only been one drug for all. We also need to consider consent, if a patient changes from one drug to another during their treatment. Biosimilars are here to stay and we see an increasing number in our everyday practice, so need to prepare ourselves for their widespread use. In future, we will see more clinical trials assessing biosimilars as a way of supporting pharmacovigilance. This new chapter in cancer treatment requires us to expand our knowledge, so that we are providing patients with the BJN support and information they need.
Conflict of interest: none Aapro M (2013) Biosimilars in oncology: current and future perspectives. GaBI Journal 2(2): 91–3. doi: 10.5639/ gabij.2013.0202.023). http://tinyurl.com/nexddov (accessed 11 February 2015) Aapro MS, Bohlius J, Cameron DA et al (2011) 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapyinduced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer 47(1): 8–32. doi: 10.1016/j.ejca.2010.10.013 Abraham J (2013) Developing oncology biosimilars: an essential approach for the future. Semin Oncol 40 Suppl 1: S5–24. doi: 10.1053/j.seminoncol.2013.09.015 NHS England (2015) Outcome of consultation on proposed changes to Cancer Drug Fund Standard Operating Procedures. http://tinyurl.com/qau7472 (acccessed 11 February 2015) Gascón P, Tesch H, Verpoort K et al (2013) Clinical experience with Zarzio® in Europe: what have we learned? Support Care Cancer 21(10): 2925–32. doi: 10.1007/s00520-013-1911-7 Generics and Biosimilars Initiative online (2012) Biosimilar policies in the UK. http://tinyurl.com/kjxhr9q (accessed 15 February 2015) Henry D,Taylor C (2014) Pharmacoeconomics of cancer therapies: considerations with the introduction of biosimilars. Semin Oncol 41 Suppl 3: S13–20. doi: 10.1053/j.seminoncol.2014.03.009 Hirsch BR, Lyman GH (2013) Will biosimilars gain momentum? J Natl Compr Canc Netw 11(10): 1291–7 Mellstedt H (2013) Anti-neoplastic biosimilars—the same rules as for cytotoxic generics cannot be applied. Ann Oncol 24 Suppl 5: v23–8. doi: 10.1093/annonc/mdt325 Rak Tkaczuk KH, Jacobs IA (2014) Biosimilars in oncology: from development to clinical practice. Semin Oncol 41 Suppl 3: S3–12. doi: 10.1053/j.seminoncol.2014.03.008 Zelenetz AD, Ahmed I, Braud EL et al (2011) NCCN Biosimilars White Paper: Regulatory,Scientific, and Patient Safety Perspectives. Journal of the National Comprehensive Cancer Network 9 Suppl 4. http://tinyurl.com/ne9c9vk (accessed 15 February 2015)
Helen Roe
Consultant Cancer Nurse/ Acute Oncology Service Lead, North Cumbria University NHS Hospitals Trust
Research Skills for Nurses and Midwives This book aims to provide nurses and midwives with a sound theoretical knowledge base for understanding, critically appraising and undertaking research in all areas of health service provision. A comprehensive insight is provided into philosophies, methodologies and methods relevant to health care, using examples from both professions. This new edition is expanded, more detailed and includes a new chapter which offers a ‘how to do’ section, which nurses and midwives, beginning to engage with research for the first time, will enjoy and find useful. The book covers the main sources of research and evidence which nurses and midwives use to develop their practice. The two main headings explore qualitative and quantitative research in depth, avoiding jargon, but building in many examples to illustrate the topics. In addition, the application of other forms of evidence is addressed, as is the role of mixed methods designs. Not only does the book encourage nurses and midwives to develop their research and evidence skills, by the time the reader has completed it, they will have the knowledge and skills to conduct their own small scale research projects.
© 2015 MA Healthcare Ltd
ISBN-13: 978-1-85642-503-2; paperback; publication: 2013; 150 pages; RRP £19.99
Order your copies by visiting
or call our Hotline
www.quaybooks.co.uk
+44(0)1722 716 935
British Journal of Nursing, 2015 (Oncology Supplement), Vol 24, No 4
S29
British Journal of Nursing. Downloaded from magonlinelibrary.com by 193.061.135.112 on November 24, 2015. For personal use only. No other uses without permission. . All rights reserved.
ancer care continually places huge financial demands on our healthcare systems, mainly owing to a growing population, people living longer and the increase cost of cancer drugs (Aapro, 2013; Hirsch and Lyman, 2013).All these factors translate to cancer care being one of the most costly specialties requiring funding (Henry and Taylor, 2014). Since 2014, a number of manufacturers have lost their patent for manufacturing cancer drugs (Aapro, 2013). They also lost data exclusivity, allowing other manufacturers to develop biosimilars for use in clinical practice (Aapro, 2013; Abrabam, 2013). This accounts for the influx of biosimilars onto the market, which are now seen as playing a key part in the treatment of cancer, and were initially only seen in the supportive care setting (Rak Tkaczuk and Jacobs, 2014). Biosimilar drugs are developed as a result of another manufacturer not being able to replicate the drug exactly (Abraham, 2013). The development process is relatively easy for small-molecule drugs, but much harder when considering the large molecules that make up biologics (Rak Tkaczuk and Jacobs, 2014). The rationale behind biosimilars is to develop a drug that exhibits a similar chemical composition profile to the patented drug, and manufacturers must demonstrate similarities in activity and pharmacokinetics i.e. mode of action, mechanism of absorption and distribution, along with metabolism and excretion. The manufacturer of the off-patent drug must demonstrate bioequivalence between the biosimilar and the previously patented drug (Mellstedt, 2013). This process enables the existing efficacy and safety data to be used as supportive evidence during the approval process (Rak Tkaczuk and Jacobs, 2014). Some feel there is a need for more comparative clinical trials to be undertaken, which will either support the economic evidence for biosimilars or not (Hirsch and Lyman, 2013). In 2011, the National Comprehensive Cancer Network (NCCN) undertook a survey of health professionals attending its annual conference to determine knowledge and concerns regarding biosimilars and their use in clinical practice. The results demonstrated that around half the health professionals surveyed were not at all, or only slightly, familiar with the development process of biosimilars.Those with knowledge of biosimilars also indicated a high level of interest in using biosimilars once they were approved. That same year, the NCCN formed the Biosimilars
S28
Work Group, which took a multiprofessional approach and produced a consensus statement outlining recommendations and support for the implementation of biosimilars into clinical practice (Zelenetz et al, 2011). Patented drugs remain identical to the original product in terms of dose, strength, route of administration and safety profile (Mellstedt, 2013). The same cannot be said of biosimilars (Aapro, 2013); although they are referred to as highly similar, they are not identical (Abraham, 2013). This means they will have the same mechanism of action and molecular similarities (Henry and Taylor, 2014), but there may be possible changes at a cellular level between batches of the same drug (Aapro, 2013) as a result of the manufacturing process (Mellstedt, 2013). Even with the same manufacturing process, these changes may occur over time, which may alter the nature and activity of the drug (Hirsch and Lyman, 2013). Companies are therefore required to demonstrate that this process does not result in any meaningful changes to either the efficacy or safety of the drug produced (Rak Tkaczuk and Jacobs, 2014). The main safety concern raised by prescribers regarding the use of biosimilars is immunogenicity owing to the immune responses caused by the possible structural changes during the manufacturing process (Rak Tkaczuk and Jacobs, 2014). These changes, no matter how small, may lead to hypersensitivity reactions not previously seen with the use of biologics (Abraham, 2013). Another concern is around interchangeability, where two products can be exchanged without affecting the health outcomes (Rak Tkaczuk and Jacobs, 2014) as potential switching of a drug part way through a patient’s planned treatment may result in a different side effects profile (Hirsch and Lyman, 2013; Mellstedt, 2013). Prescribers are concerned that this may happen without their knowledge i.e. automatic substitution at the dispensing level (Abraham, 2013; Gascón et al, 2013). These concerns are being address, for example by the European Organisation for Research and Treatment of Cancer (EORTC) granulocyte stimulating factor G-CSF clinical guidelines, which state that automatic substitution should not happen without the prescribers consent (Aapro et al, 2011). In the UK, these concerns are considered by a panel of experts on behalf of the National Institute for Health and Care Excellence (NICE).
The panel is responsible for undertaking a systematic review of the evidence relating to a drug’s potential benefit and possible safety concerns before recommending it be funded by the NHS. These reviews apply equally to both original biologic and biosimilars drugs (Henry and Taylor, 2014).The Medicines and Healthcare products Regulatory Agency (MHRA) has also issued guidance to ensure biosimilars are monitored and tracked in accordance with the European Union pharmacovigilance legislation (Generics and Biosimilars Initiative online, 2012). Currently biosimilars used in clinical practice are mainly in the supportive setting i.e. Binocrit® (biosimilars epoetin alpha) and Zarzio® (biosimilar filgrastim) (Aapro, 2013). Abraham (2013) explained the connection between the launch of a biosimilars of filgrastim and the reduction in spending per patient, together with an increase in accessing the drug to support patients receiving chemotherapy who are at risk of neutropenia. This change in prescribing practice has also shown the drug is used earlier in the patient’s management (Henry and Taylor, 2014). Gascón et al (2013) outlined the process that resulted in Zarzio gaining approval for use in clinical practice. This process compared the quality of the product with Neupogen® (the originator) and demonstrated that the product in terms of physiochemical and biological comparability was favourable, as was its efficacy. The use of Zarzio in Europe has shown that a biosimilar drug can meet regulatory requirements and, importantly, has shown favourable efficacy and safety when compared with the originator (Rak Tkaczuk and Jacobs, 2014). Current evidence suggests that biosimilars offer both a safe and effective alternative to original drugs (Gascón et al, 2013) with added reassurance around the development, manufacture and licensing, which appear to be even more stringent than those for traditional drugs (Aapro, 2013). Many concerns may be alleviated through adequate pharmacovigiliance to truly monitor the patient’s experience of receiving biosimilars. However, this will take time and is reliant on good reporting and analysis of acquired data (Hirsh and Lyman, 2013). Traceability of biosimilars, in terms giving individual product names to biosimilars, will also assist in addressing some concerns and support pharmacovigiance (Gascón et al, 2013). The increased use of biosimilars may be seen as a possible cost saving in the treatment
© 2015 MA Healthcare Ltd
The rise of biosimilars in cancer care
British Journal of Nursing, 2015 (Oncology Supplement), Vol 24, No 4
British Journal of Nursing. Downloaded from magonlinelibrary.com by 193.061.135.112 on November 24, 2015. For personal use only. No other uses without permission. . All rights reserved.
COMMENT of cancer, offering greater access to treatments and providing the option for treatments to be introduced earlier (Henry and Taylor, 2014; Rak Tkaczuk and Jacobs, 2014). One option is that the money saved by the introduction of biosimilars in the supportive setting may be reinvested in the use of treatments to manage the cancer i.e. monoclonal antibodies (Abraham, 2013; Aapro, 2013), which are currently some of the most expensive systemic anti-cancer treatments. As a result of the number of drugs losing their patent, the emphasis is now on manufacturing biosimilars to replace other drugs i.e. monoclonal antibodies and not just supportive treatments (Aapro, 2013). The changes to the market in terms of offpatent drugs and the development of biosimilars may encourage manufacturers to review their pricing as a way of ensuring their products remain competitive (Hirsch and Lyman, 2013). The pricing of drugs was discussed during the recent review of the Cancer Drug Fund (CDF) in England announced in January 2015, which saw the removal of some drugs. This decision to remove certain drugs was based on newer evidence relating to their properties and their cost-effectiveness, yet some manufacturers felt the costs could not be lowered owing to the expense of progressing a drug from the laboratory to the clinical setting (NHS England,
2015). Other incentives to use biosimilars are when the care is delivered as a ‘bundle’ and the provider may wish to use a slightly cheaper drug with equal efficacy (Hirsch and Lyman, 2013), resulting in a cost saving for the provider. We need to know when a patient is receiving a biosimilar drug, and have an understanding of the drug mechanisms and potential differences in the side effect profiles. We need this knowledge in order to act as advocates for patients, offering them continued support and advice regarding their current or future care. Biosimilars have been used in supportive care, but are now moving into the systemic anticancer treatments option; there is a need for us to keep abreast of changes, especially as there may be different biosimilars for different tumour groups, when previously there would have only been one drug for all. We also need to consider consent, if a patient changes from one drug to another during their treatment. Biosimilars are here to stay and we see an increasing number in our everyday practice, so need to prepare ourselves for their widespread use. In future, we will see more clinical trials assessing biosimilars as a way of supporting pharmacovigilance. This new chapter in cancer treatment requires us to expand our knowledge, so that we are providing patients with the BJN support and information they need.
Conflict of interest: none Aapro M (2013) Biosimilars in oncology: current and future perspectives. GaBI Journal 2(2): 91–3. doi: 10.5639/ gabij.2013.0202.023). http://tinyurl.com/nexddov (accessed 11 February 2015) Aapro MS, Bohlius J, Cameron DA et al (2011) 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapyinduced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer 47(1): 8–32. doi: 10.1016/j.ejca.2010.10.013 Abraham J (2013) Developing oncology biosimilars: an essential approach for the future. Semin Oncol 40 Suppl 1: S5–24. doi: 10.1053/j.seminoncol.2013.09.015 NHS England (2015) Outcome of consultation on proposed changes to Cancer Drug Fund Standard Operating Procedures. http://tinyurl.com/qau7472 (acccessed 11 February 2015) Gascón P, Tesch H, Verpoort K et al (2013) Clinical experience with Zarzio® in Europe: what have we learned? Support Care Cancer 21(10): 2925–32. doi: 10.1007/s00520-013-1911-7 Generics and Biosimilars Initiative online (2012) Biosimilar policies in the UK. http://tinyurl.com/kjxhr9q (accessed 15 February 2015) Henry D,Taylor C (2014) Pharmacoeconomics of cancer therapies: considerations with the introduction of biosimilars. Semin Oncol 41 Suppl 3: S13–20. doi: 10.1053/j.seminoncol.2014.03.009 Hirsch BR, Lyman GH (2013) Will biosimilars gain momentum? J Natl Compr Canc Netw 11(10): 1291–7 Mellstedt H (2013) Anti-neoplastic biosimilars—the same rules as for cytotoxic generics cannot be applied. Ann Oncol 24 Suppl 5: v23–8. doi: 10.1093/annonc/mdt325 Rak Tkaczuk KH, Jacobs IA (2014) Biosimilars in oncology: from development to clinical practice. Semin Oncol 41 Suppl 3: S3–12. doi: 10.1053/j.seminoncol.2014.03.008 Zelenetz AD, Ahmed I, Braud EL et al (2011) NCCN Biosimilars White Paper: Regulatory,Scientific, and Patient Safety Perspectives. Journal of the National Comprehensive Cancer Network 9 Suppl 4. http://tinyurl.com/ne9c9vk (accessed 15 February 2015)
Helen Roe
Consultant Cancer Nurse/ Acute Oncology Service Lead, North Cumbria University NHS Hospitals Trust
Research Skills for Nurses and Midwives This book aims to provide nurses and midwives with a sound theoretical knowledge base for understanding, critically appraising and undertaking research in all areas of health service provision. A comprehensive insight is provided into philosophies, methodologies and methods relevant to health care, using examples from both professions. This new edition is expanded, more detailed and includes a new chapter which offers a ‘how to do’ section, which nurses and midwives, beginning to engage with research for the first time, will enjoy and find useful. The book covers the main sources of research and evidence which nurses and midwives use to develop their practice. The two main headings explore qualitative and quantitative research in depth, avoiding jargon, but building in many examples to illustrate the topics. In addition, the application of other forms of evidence is addressed, as is the role of mixed methods designs. Not only does the book encourage nurses and midwives to develop their research and evidence skills, by the time the reader has completed it, they will have the knowledge and skills to conduct their own small scale research projects.
© 2015 MA Healthcare Ltd
ISBN-13: 978-1-85642-503-2; paperback; publication: 2013; 150 pages; RRP £19.99
Order your copies by visiting
or call our Hotline
www.quaybooks.co.uk
+44(0)1722 716 935
British Journal of Nursing, 2015 (Oncology Supplement), Vol 24, No 4
S29
British Journal of Nursing. Downloaded from magonlinelibrary.com by 193.061.135.112 on November 24, 2015. For personal use only. No other uses without permission. . All rights reserved.
