Open access Original research ESMO Open: first published as 10.1136/esmoopen-2018-000460 on 6 March 2019. Downloaded from http://esmoopen.bmj.com/ on December 1, 2020 by guest. Protected by copyright. Knowledge and use of biosimilars in oncology: a survey by the European Society for Medical Oncology Rosa Giuliani,1 Josep Tabernero,2 Fatima Cardoso,3 Keith Hanson McGregor,4 Malvika Vyas,5 Elisabeth G E de Vries6 ►► Additional material is Abstract published online only. To view Key questions Background Biosimilars can potentially improve please visit the journal online the sustainability of cancer care; however, uptake is (http://​dx.​doi.​org/​10.​1136/​ What is already known about this subject? sometimes limited by safety concerns and a lack of esmoopen-​2018-​000460). ►► Biosimilars may potentially reduce care costs and understanding of the concept of extrapolation. The improve patient access. To cite: Giuliani R, Tabernero J, European Society for Medical Oncology (ESMO) conducted ►► However, uptake of biosimilars in oncology has been Cardoso F, et al. Knowledge a survey to assess the current level of knowledge, limited by safety concerns. and use of biosimilars in understanding and comfort of use of biosimilars among ►► In particular, surrounding switching from a biosim- oncology: a survey by the prescribers specialised in oncology. European Society for Medical ilar to its reference medicine or vice versa, and a Methods A 19-question survey was developed using Oncology. ESMO Open lack of understanding around the requirements for the SurveyMonkey online platform (https://www.​ 2019;4:e000460. doi:10.1136/ development, including extrapolation of indications. surveymonkey.​com/). Data collection occurred between esmoopen-2018-000460 September and October 2017 and included paper and What does this study add? online responses. ►► This European Society for Medical Oncology survey Received 19 October 2018 Results Overall, 393 responses were received from found encouraging levels of prescriber use and gen- Revised 25 January 2019 prescribers. Overall, 49.0% of prescribers use biosimilars eral knowledge of biosimilars; however, a substan- Accepted 28 January 2019 in clinical practice and most (79.2%) rate their general tial need for further education remains, especially knowledge of biosimilars as average to very high. Potential for improving prescriber understanding of extrapo- increased risk of immunogenicity remains a significant lation of indications. concern of switching. Gaps in knowledge identified by the ►► Discrepancies in responses were found among Asia- © Author (s) (or their survey include biosimilar development, clinical trial design Pacific and European prescribers. employer(s)) 2019. Re-use and endpoint selection, and requirements for extrapolation, ►► Asia-Pacific prescribers appear more confident in permitted under CC BY. which should form the focus of future educational their understanding of the biosimilar development Published by BMJ on behalf initiatives. A substantial demand remains for further process, the concept of extrapolation of indica- of the European Society for educational activities with equal preference for online and Medical Oncology. tions and switching, but less confident on European 1 face-to-face initiatives. A higher rate of biosimilar use Medicines Agency definitions. Medical Oncology, San Camillo- (56.3% vs 46.5%), knowledge of biosimilar development ►► A worldwide effort should be undertaken to align Forlanini Hospital, Rome, Italy 2 and trial design, and comfort with extrapolation, but definitions and regulatory standards. Vall d’Hebron University a lower knowledge of European Medicines Agency Hospital and Institute of definitions, was found among prescribers from Asia-Pacific How might this impact on clinical practice? Oncology (VHIO), Universitat versus those from Europe. ►► Educational initiatives focused on the knowledge Autònoma de Barcelona, Barcelona, Spain Conclusion Encouraging levels of prescriber use and gaps identified in this survey are essential for suc- 3 Breast Unit, Champalimaud general knowledge of biosimilars were found, but a cessful integration and uptake of biosimilars in Clinical Center/Champalimaud substantial need for further education remains. Efforts oncology, which can potentially improve the sustain- Foundation, Lisbon, Portugal should be made worldwide to align terms, definitions and ability of cancer care by increasing the accessibility 4 Chief Executive Officer, guidelines for the development and approval of biosimilars. of therapeutic and supportive care and providing European Society for Medical lower-cost alternatives to their reference medicines. Oncology (ESMO), Lugano, Switzerland Introduction 5 Head of Public Policy, European Cancer treatment has been advanced by, but Society for Medical Oncology, become reliant on, biologics.1 2 Biologics are in biologics being expensive,2 5 adding to the Lugano, Switzerland 6 typically large proteins such as monoclonal already high costs of cancer treatment. Department of Medical Oncology, University Medical antibodies, interferons and recombinant Cancer care cost is rapidly becoming a Center Groningen, University hormones.3 Processes for biologic production significant issue driven by rising cancer inci- of Groningen, Groningen, The involve living systems and complex proce- dence, ageing populations and the increasing Netherlands dures requiring the utmost precision to guar- price of treatments.5 Patent expiration has Correspondence to antee final product consistency and quality.3 4 occurred or is approaching for many biologics Professor Elisabeth G E de Vries; ​ These complex manufacturing processes, as used in oncology.6 It has been proposed that e.​g.​e.​de.​vries@​umcg.​nl well as their long development times, result the sustainability of cancer care worldwide Giuliani R, et al. ESMO Open 2019;4:e000460. doi:10.1136/esmoopen-2018-000460 1 Open access ESMO Open: first published as 10.1136/esmoopen-2018-000460 on 6 March 2019. Downloaded from http://esmoopen.bmj.com/ on December 1, 2020 by guest. Protected by copyright. can potentially be improved through the use of safe and Methods effective biosimilars, which expand the treatment options ESMO developed a 19-question survey using the Survey- available to clinicians and patients, increase accessibility Monkey online platform (https://www.​ surveymonkey.​ of therapeutic and supportive care, and provide lower- com/), which sought information regarding responders’ cost alternatives to their reference medicines.2 5 7 8 use and basic knowledge of biosimilars, understanding of A biosimilar is a biologic that matches its reference biosimilar development and level of comfort with extrap- medicine in terms of quality, activity, safety and effi- olation, interchangeability and switching (see online cacy.9–11 In 2006, a recombinant human growth hormone supplementary appendix). (Omnitrope) was the first biosimilar to receive Euro- Data collection occurred between September and pean Medicines Agency (EMA) approval,12 followed by October 2017 and included both paper and online EMA approval of biosimilars for epoetin alfa in 2007 responses. During the ESMO 2017 Congress, attendees and recombinant human granulocyte colony-stimulating completed paper copies of the survey; results were then factor (rhG-CSF) in 2009.13 14 The biosimilar rhG-CSF inputted into the SurveyMonkey platform. Additionally, (Zarxio) was the first biosimilar to receive approval from a link to the online survey was sent in an email to ESMO the US Food and Drug Administration (FDA).15 members and their wider professional network. Results Regulatory requirements for biosimilars are evolving were summarised using descriptive statistics. and becoming more familiar among healthcare profes- The survey contained a mixture of checkbox answers sionals (HCPs). The EMA, FDA and WHO require and questions asking responders to rank their level of substantial evidence demonstrating that a biosimilar agreement, knowledge, comfort or importance of each matches its reference medicine.9–11 The objective of a statement from 1 to 5 or 10. For these questions, results biosimilar development programme is to demonstrate no were pooled and a weighted average (WA) score out of clinically meaningful differences based on the ‘totality of 5 or 10 was assigned. An open comments box at the end evidence’ approach, that is, a comprehensive comparison of the survey asked responders to provide suggestions for of the proposed biosimilar and the reference medicine future educational initiatives. with respect to structure, function, pharmacokinetics, pharmacodynamics, clinical immunogenicity, safety and efficacy.9–11 Unlike the standard requirements for Results drug approval, the development process for biosimilars Demographics, basic knowledge and use demands a relatively larger amount of preclinical than Overall, 495 responses were collected. Of the 480 clinical data. responders who mentioned their country, most were Despite the potential for reducing care costs and from Europe (n=321), then Asia (n=84), America (n=55), improving patient access, uptake of biosimilars in oncology Africa (n=13) and Australia (n=7). has been limited potentially by a lack of understanding These analyses include responses from prescribing physi- of their development and of the regulatory assessment, cians only and evaluate responses from all prescribers, including requirements for extrapolation of indications.7 European and Asia-Pacific prescribers. Overall, 80.0% Extrapolation is the approval, by a regulatory agency, of (393/491, 4 skipped) of responders were prescribing a biosimilar in one or more indications of the reference physicians (Europe: 79.7%, n=255; Asia-Pacific: 87.9%, biologic without the requirement to carry out clinical n=80), with most being ESMO members (92.0%, n=357) trials of the biosimilar in all those indications.16 17 If simi- and specialised in oncology (94.3%, n=367). larity between the biosimilar and its reference biologic is When asked to rate their overall knowledge of biosim- credibly shown through ‘totality of evidence’ in one indi- ilars, the most commonly selected option on a scale of 1 cation, extrapolation permits approval of the biosimilar (very low) to 5 (very high) was option 3 (45.5%, 177/389, in all other indications held by the reference biologic.18 4 skipped; figure 1A). Options 3, 4 and 5 were selected Extrapolation has the potential to reduce the costs asso- by 79.2% (n=308; sum of responses) of prescribers indi- ciated with biosimilar development, increasing access to cating that most consider themselves to have an average biologic therapies and reducing cancer care costs.7 to very high level of knowledge of biosimilars. In total, Uncertainties exist among HCPs regarding switching, 74.6% (291/390, 3 skipped) of prescribers were able to the decision to administer a biosimilar in a patient previ- identify the most appropriate definition of ‘biosimilar’ ously treated with the reference biologic or vice versa, (‘highly similar to an approved biological medicine, with and the potential for reduced efficacy or increased no clinically meaningful differences in safety and efficacy immunogenicity in both the oncology and non-oncology profile’). This definition was selected by 77.9% (197/253, settings.3 19–22 2 skipped) of European and 64.6% (51/79, 1 skipped) of In order to assess the current knowledge, under- Asia-Pacific prescribers. standing and comfort of use of biosimilars in oncology, Overall, 49.0% (191/390, 3 skipped) of prescribers use with a particular focus on extrapolation and switching, biosimilars in routine clinical practice (excluding clinical the European Society for Medical Oncology (ESMO) trials; figure 2). A higher proportion of prescribers from conducted a survey among its members and attendees at Asia-Pacific (56.3%, 45/80) use biosimilars versus those the 2017 ESMO Congress in Madrid, Spain. from Europe (46.5%, 118/254, 1 skipped; figure 2). 2 Giuliani R, et al. ESMO Open 2019;4:e000460. doi:10.1136/esmoopen-2018-000460 Open access ESMO Open: first published as 10.1136/esmoopen-2018-000460 on 6 March 2019. Downloaded from http://esmoopen.bmj.com/ on December 1, 2020 by guest. Protected by copyright. Figure 1 Prescribers’ responses rating their level of knowledge/understanding on a scale of 1–5. Prescribers’ responses, by region, when asked to rate their knowledge/understanding of (A) biosimilars overall; (B) the biosimilar development process and threshold of clinical evidence required for approval; (C) clinical trial design and endpoint selection for biosimilar studies; (D) requirements needed to be met for extrapolation of indications to be granted for a biosimilar. Compared with the entire European group, rate of use was a scale of 1 (very low) to 5 (very high; figure 1B). Option lower among prescribers from the UK (31.3%, 10/32). 3 was the most frequent choice by Asia-Pacific and Euro- Biosimilars are not used by 24.1% (94/390, 3 skipped) of pean prescribers (43.9% vs 37.0%; figure 1B) with the prescribers due to lack of approval or reimbursement in second most commonly selected choices being option 4 their country (figure 2). (24.2%) and option 2 (22.2%), respectively (figure 1B). On a scale of 1 (not at all) to 5 (very), prescribers were Clinical safety and efficacy data are the best under- asked to rate their comfort with the concept of using an stood data types by all prescribers (WA [out of 5] 3.67), EMA-approved biosimilar to treat a patient suitable for followed by immunogenicity data (WA 3.10). However, the reference biologic. Options 4 and 5 were chosen the two regions differed on the least understood type of by 57.4% (217/378, 15 skipped, sum of responses) of data (Europe: physicochemical, WA 2.64; Asia-Pacific: prescribers (figure 3A). in vitro, WA 2.36). In addition, clinical study safety (WA Biosimilar development [out of 10] 8.80) and efficacy (WA 8.65; table 1) data are Most prescribers feel they have an average to moderate considered the most important among prescribers in level of knowledge of the biosimilar development determining the suitability of a biosimilar for use. The process and the threshold of clinical evidence required type of data considered least important is physicochem- for approval of a biosimilar, with 61.1% (204/334, 59 ical data demonstrating structural similarity (WA 7.23; skipped, sum of responses) selecting options 3 and 4 on table 1). Giuliani R, et al. ESMO Open 2019;4:e000460. doi:10.1136/esmoopen-2018-000460 3 Open access ESMO Open: first published as 10.1136/esmoopen-2018-000460 on 6 March 2019. Downloaded from http://esmoopen.bmj.com/ on December 1, 2020 by guest. Protected by copyright. Figure 2 Level of routine use of biosimilars by prescribers in clinical practice to treat patients. From three options, 45.2% (146/323, 70 skipped) to moderate level of knowledge regarding clinical trial of prescribers were able to select the most appropriate design and endpoint selection for biosimilar studies, with definition of ‘sensitive indication’ in terms of biosimilar 59.8% (195/326, 16 skipped, sum of responses) selecting development (‘the population that is most representative options 3 and 4 (figure 1C). Nearly half of the prescribers of the patients to whom the biologic is most frequently (49.7%, 161/324, 69 skipped) chose ‘the endpoint consid- prescribed’). This definition was selected by 42.1% ered most sensitive for detecting differences between the (88/209, 46 skipped) of European and 60.0% (39/65, 15 biosimilar and reference biologic, and least influenced by skipped) of Asia-Pacific prescribers. The second preferred patient or disease-related factors’ as the most appropriate definition (‘a population where product-related differ- for studies comparing the clinical efficacy of a biosimilar ences in clinical performance can be best detected’) was with its reference medicine. chosen by 31.3% (101/323, 70 skipped) of all prescribers Moreover, 33.4% (108/323, 70 skipped) of prescribers (Europe: 33.5%, 70/209, 46 skipped; Asia-Pacific: 26.2%, feel that the most appropriate indication for a study 17/65, 15 skipped). comparing the clinical efficacy and safety of a biosimilar On a scale of 1 (very low) to 5 (very high), responses with a reference biologic is ‘the indication representing suggest that most prescribers feel they have an average the most sensitive population for detecting any potential Figure 3 Prescribers’ responses rating their level of comfort on a scale of 1–5. Prescribers’ responses, by region, when asked to rate their comfort with (A) the concept of using an EMA-approved biosimilar to treat a patient suitable for the reference biologic; (B) using an EMA-approved biosimilar in extrapolated indications that the reference biologic is approved for. EMA, European Medicines Agency. 4 Giuliani R, et al. ESMO Open 2019;4:e000460. doi:10.1136/esmoopen-2018-000460 Open access ESMO Open: first published as 10.1136/esmoopen-2018-000460 on 6 March 2019. Downloaded from http://esmoopen.bmj.com/ on December 1, 2020 by guest. Protected by copyright. Table 1 Prescribers’ responses rating the importance and sensitivity of different data types in determining the suitability of a biosimilar for use Importance Sensitivity Type of data (weighted average) All Europe Asia-Pacific All Europe Asia-Pacific Physicochemical data demonstrating 7.23 7.05 7.30 7.24 7.07 7.56 structural similarity In vitro and in vivo data demonstrating 7.76 7.74 7.66 7.58 7.46 7.82 similarity in biological activity PK and PD data demonstrating 7.94 7.85 8.10 7.83 7.75 8.10 similarity Clinical study data demonstrating 8.65 8.56 8.72 8.61 8.57 8.75 similar efficacy Clinical study data demonstrating 8.80 8.78 8.83 8.75 8.72 8.79 similar safety Clinical study data demonstrating 8.24 8.24 8.10 8.30 8.23 8.41 similar immunogenicity Clinical study data demonstrating 8.07 8.02 8.27 8.11 8.02 8.36 the ability to switch from reference to biosimilar and vice versa without impairing safety or efficacy Weighted average of prescribers’ responses, by region, on a scale of 1 (not important/sensitive) to 10 (very important/sensitive). PD, pharmacodynamic; PK, pharmacokinetic. difference between the products’. The next most frequent Interchangeability and switching response, selected by 27.9% (90/323, 70 skipped), was Respondents were presented with correct EMA defini- ‘comparative efficacy and safety should be studied in tions of interchangeability and switching, and an incor- every indication of the reference biologic’, suggesting rect definition of substitution. Only 36.3% (110/303, 90 that there is a lack of understanding surrounding the skipped) of prescribers were able to identify the incor- concept of extrapolation of indications. rect definition and the other two correct definitions were also widely chosen (interchangeability: 29.7%, 90/303, 90 Extrapolation of indications skipped; switching: 34.0%, 103/303, 90 skipped). Similar Most prescribers (61.7%, 192/311, 82 skipped) were able proportions of European (36.0%, 71/197, 58 skipped) to identify the most appropriate definition of ‘extrap- and Asia-Pacific (35.5%, 22/62, 18 skipped) prescribers olation of indications’ (‘authorisation of a biosimilar were able to successfully identify the incorrect definition in indications of the reference biologic in the absence of substitution. However, the same proportion of Asia-Pa- of specific clinical trial/data for the biosimilar in those cific prescribers (35.5%, 22/62, 18 skipped) believed the indications’). Fewer Asia-Pacific prescribers selected this definition of switching was incorrect. definition versus European prescribers (53.2% vs 65.4%), although it was the preferred option in both groups. Regarding switching a patient from a biosimilar to Despite the high proportion of prescribers being able to a reference biologic or vice versa, the statement most define ‘extrapolation of indications’, most consider their agreed with by prescribers was “I do not anticipate that understanding of extrapolation to be below average, with switching will have a significant effect on the treatment 62.3% (190/305, 88 skipped, sum of responses) selecting benefit the patient receives from the product” (WA options 2 and 3 on a scale of 1 (very low) to 5 (very high; [out of 5] 3.50). This statement was the most commonly figure 1D). chosen option by both European (WA 3.47) and Asia-Pa- Overall, responses indicate that prescribers feel cific prescribers (WA 3.55). However, among prescribers comfortable using a biosimilar in an extrapolated indi- from Asia-Pacific, there was a similar level of agreement cation. On a scale of 1 (not at all) to 5 (very), options (WA 3.54) with the statement “I do not anticipate that 3, 4 and 5 were chosen by 76.7% (237/309, 84 skipped, switching will lead to emergence of additional adverse sum of responses) of prescribers (figure 3B). These three events”. options were chosen by 74.3% (150/202, 53 skipped, Among all prescribers, equal levels of concern were sum of responses) of European and 82.8% (53/64, 16 expressed for the potential for adverse events (AEs) skipped, sum of responses) of Asia-Pacific prescribers and increased risk of immune reactions when switching (figure 3B), indicating that Asia-Pacific prescribers may (WA 3.35; table 2). European prescribers were mainly feel more comfortable with the concept of extrapolation concerned with the potential increased risk of immune than those from Europe. reactions (WA 3.39) whereas Asia-Pacific prescribers Giuliani R, et al. ESMO Open 2019;4:e000460. doi:10.1136/esmoopen-2018-000460 5 Open access ESMO Open: first published as 10.1136/esmoopen-2018-000460 on 6 March 2019. Downloaded from http://esmoopen.bmj.com/ on December 1, 2020 by guest. Protected by copyright. communicated a higher interest in receiving training on Table 2 Prescribers’ responses rating their concern of potential consequences when switching a patient’s the efficacy and safety of biosimilars while Asia-Pacific treatment from a reference biologic to a biosimilar or vice prescribers were more interested in training tailored for versa developing countries. Potential consequence (weighted average) All Europe Asia-Pacific Discussion This ESMO survey shows that nearly half of prescribers Potential loss of 3.29 3.23 3.30 (49.0%) use biosimilars in their clinical oncology prac- clinical efficacy tice; lack of approval and reimbursement is a barrier to Potential for adverse 3.35 3.32 3.35 use. Responses suggest that most prescribers (79.2%) feel events they have an average to very high level of general biosim- Potential for increased 3.35 3.39 3.17 ilar knowledge, with nearly three quarters (74.6%) able risk of immune reactions to identify the most appropriate definition of ‘biosimilar’. Overall, 57.4% of prescribers feel comfortable using an Weighted average of prescribers’ responses, by region, on a scale EMA-approved biosimilar. of 1 (not at all) to 5 (very). Most prescribers feel they only have an average to moderate level of knowledge about biosimilar devel- were primarily concerned with potential AEs (WA 3.35; opment, the level of clinical evidence required for a table 2), despite a high level of agreement with not antici- biosimilar approval, clinical trial design and selection of pating additional AEs on a switch in the previous question. endpoints; these therefore present as topics for future educational activities. Indeed, less than half (45.2%) of Further education prescribers were able to identify the most appropriate Overall, 86.7% (195/225, 168 skipped) of prescribers definition of ‘sensitive indication’. Uncertainties were would like ESMO to provide more educational activities also demonstrated in differentiating ‘interchangeability’, concerning biosimilars; a much higher proportion of ‘substitution’ and ‘switching’. Despite nearly two-thirds of Asia-Pacific prescribers expressed this (97.9%, 47/48, 32 prescribers being able to identify the most appropriate skipped) versus European prescribers (82.9%, 121/146, definition of ‘extrapolation of indications’, most rated 109 skipped). their understanding of the requirements for extrapo- Prescribers suggested numerous topics for future lation of indications as below average. However, most educational activities, including clinical trial design and prescribers feel comfortable using a biosimilar in an endpoints, bioequivalence criteria and studies, approval extrapolated indication. Therefore, it seems that many procedures, principles of pricing and reimbursement, prescribers trust and accept the scientific principle of and treatment outcome comparisons between biosimilars extrapolation though may not fully understand it. and their reference medicines. Communication chan- The main concerns oncology prescribers have with nels suggested included online educational activities and switching are the potential for AEs and increased risk materials (courses, quizzes, articles, guideline handbooks of immune reactions. Currently, the majority of data and updates on key developments; n=56) and face-to-face available on switching are from real-world and clinical educational activities (congress sessions, preceptorships, studies in immune-mediated inflammatory diseases, such workshops and seminars; n=51). European prescribers as rheumatoid arthritis, inflammatory bowel disease and psoriasis, which have found no clinically meaningful effects when switching between a biosimilar and its refer- Table 2 Prescribers’ responses rating their concern ence biologic.23–42 Presently, there is one published study of potential consequences when switching a patient’s on switching in oncology, which reported no meaningful treatment from a reference biologic to a biosimilar or vice differences in efficacy, safety or immunogenicity when versa switching biosimilar rhG-CSF with its reference biologic Potential to prevent severe neutropenia in patients with breast consequence cancer undergoing myelosuppressive chemotherapy.43 A (weighted average) All Europe Asia-Pacific recent systematic literature review of 90 switching studies, Potential loss of 3.29 3.23 3.30 treating 14 disease indications and enrolling over 14 000 clinical efficacy patients and healthy volunteers, concluded that there is Potential for adverse 3.35 3.32 3.35 little risk of increased immunogenicity or treatment-re- events lated AEs, or reduction in efficacy, when switching Potential for increased 3.35 3.39 3.17 between reference medicines and biosimilars.21 An risk of immune increase in the confidence of switching biosimilar medi- reactions cines with their reference biologics among the oncology Weighted average of prescribers’ responses, by region, on a scale community, like in other disease areas, may occur after of 1 (not at all) to 5 (very). increased availability of results from further real-world 6 Giuliani R, et al. ESMO Open 2019;4:e000460. doi:10.1136/esmoopen-2018-000460 Open access ESMO Open: first published as 10.1136/esmoopen-2018-000460 on 6 March 2019. Downloaded from http://esmoopen.bmj.com/ on December 1, 2020 by guest. Protected by copyright. data and world-evidence studies that will ultimately help biosimilar development and trial design, as well as under- to guide clinical decision-making. standing and comfort of extrapolation of indications, Regarding knowledge, use and comfort with biosimi- were similar between prescribers specialised in oncology lars, some differences in responses were found between and haematology. However, a higher proportion of European and Asia-Pacific prescribers. First, a higher rate haematology versus oncology prescribers feel they have of biosimilar use in routine clinical practice was found a high to very high level of comfort using an EMA-ap- among Asia-Pacific (56.3%) versus European prescribers proved biosimilar (72.8% vs 57.4%) and use biosimilars (46.46%). This may be a result of numerous regulatory in routine practice (63.6% vs 49.0%). bodies in Asia heavily investing in accelerated development Overall, the level of prescriber knowledge on biosimi- of biosimilars.44 Furthermore, a lower rate of biosimilar lars ascertained by this survey is encouraging. However, use was found among prescribers from the UK (31.3%) a substantial need for continued education emerged compared with the whole group of European prescribers. as well. Future efforts should focus in particular on Responses also suggest that Asia-Pacific prescribers may improving prescriber understanding of extrapolation of be more confident in their understanding of biosimilar indications as well as physicochemical data, which was development than European prescribers. found to be the least understood data type in determining However, in most questions concerning EMA defi- the suitability of a biosimilar for use when in fact it is nitions, a lower proportion of Asia-Pacific prescribers considered by regulatory authorities as the most determi- answered correctly versus European prescribers. The nant data type required. This survey found a substantial only instance where this was not the case was the defi- demand among prescribers for educational activities and nition of ‘sensitive indication’, correctly answered by materials regarding biosimilars, especially in Asia-Pacific. 60.0% of Asia-Pacific and 42.1% of European prescribers, Responses suggest that preference is fairly even between indicating that Asia-Pacific prescribers may have a better online (56 responses) and face-to-face (51 responses) understanding of the clinical evidence required for a educational activities. The low response to this question biosimilar to gain approval and clinical trial design. Lastly, is potentially due to its open comment box design which responses suggest that prescribers from Asia-Pacific are is more demanding for respondents and, being the final more comfortable with the concept of extrapolation than question, it is feasible that responders ran out of time. those from Europe. Prescribers from the two different regions had differing These differences in responses, particularly regarding preferences for topics that future training initiatives EMA definitions, may be a result of differing guidelines should focus on. European prescribers displayed a high available on biosimilars in each region. Europe follows interest in receiving training on the efficacy and safety standardised regulations outlined by the EMA for biosim- of biosimilars, while many from Asia-Pacific conveyed an ilar approval whereas the regulations in Asia-Pacific coun- interest for more training adapted for developing coun- tries differ greatly in the data types required.44 Since tries. ESMO is undertaking a range of educational initia- 2008, guidance ensuring the quality, safety and efficacy tives including two previous sessions during the ESMO of biosimilar medicines has been available in the Asia-Pa- 2017 meeting in Madrid and ESMO Asia 2017, and cific region.45 EMA guidance was followed initially in another two Colloquia during the 2018 annual meeting many countries in the Asia-Pacific region prior to them in Munich, Germany, and ESMO Asia 2018, to improve implementing their own individual guidelines.45 Coun- the understanding of biosimilars within the community. tries including South Korea, Japan and Malaysia estab- ESMO is also working on developing patient materials to lished their own guidance by taking elements from EMA help their understanding of biosimilars. and WHO guidelines.45–48 In August 2016, India updated Limitations of the survey include the fact that no its initial guidance originally published in 2012 to ensure hypothesis was tested and the questionnaire was purely a clearer and more thorough regulatory pathway, and to developed to document the current level of biosim- make parallel with other guidelines available around the ilar knowledge, use and comfort; not all replies were world.49 complete, so data could not be analysed in its entirety; and Currently, the requirements outlined by regulatory responses were limited to ESMO members, their wider authorities in different regions regarding biosimilar network and participants at the ESMO 2017 Congress, so approval vary.9 47 A worldwide effort should be under- may not accurately represent all prescribers worldwide. taken to align definitions and standards for the develop- ment and approval of biosimilars. This could potentially reduce confusion surrounding scientific terms and concepts, lead to better understanding of the biosimilar Conclusion development process and ultimately increase accessibility In conclusion, this survey conducted by ESMO found an and affordability of cancer care.8 encouraging level of prescriber use and general knowl- Differences in responses were also noted between edge of biosimilars in oncology; however, need for further prescribers specialised in oncology and haematology. education remains. Future educational initiatives should Of the 393 prescribers who responded, 22 (5.6%) were focus on improving prescriber understanding of extrapo- specialised in haematology. Overall, knowledge of lation of indications as well as physicochemical data. Giuliani R, et al. ESMO Open 2019;4:e000460. doi:10.1136/esmoopen-2018-000460 7 Open access ESMO Open: first published as 10.1136/esmoopen-2018-000460 on 6 March 2019. Downloaded from http://esmoopen.bmj.com/ on December 1, 2020 by guest. Protected by copyright. Lastly, some differences in responses between Euro- 6. Chopra R, Lopes G. Improving access to cancer treatments: the role of biosimilars. J Glob Oncol 2017;3:596–610. pean and Asia-Pacific prescribers may be attributed to 7. Curigliano G, O'Connor DP, Rosenberg JA, et al. Biosimilars: differences in guidance available in the two regions. Extrapolation for oncology. Crit Rev Oncol Hematol 2016;104:131–7. Efforts should be made worldwide to align definitions and 8. Rak Tkaczuk KH, Jacobs IA. Biosimilars in oncology: from development to clinical practice. Seminars in Oncology regulatory standards for the development and approval 2014;41(Suppl 3):S3–S12. of biosimilars. Continued education will lead to more 9. European Medicines Agency, 2014. Guideline on similar biological medicinal products containing biotechnology-derived proteins informed discussion and decision-making regarding as active substance: non-clinical and clinical issues. Available: biosimilars, which will help their successful integration http://www.​ema.​europa.​eu/​ema/​index.​jsp?​curl=​pages/​regulation/​ and uptake in oncology.8 general/​general_​content_​000886.​jsp&​mid=​WC0b01ac058002956b [Accessed Sep 2018]. 10. US Food and Drug Administration, 2015. Scientific considerations Correction notice This article has been corrected since it first published online. in demonstrating biosimilarity to a reference product: guidance The open access licence type has been amended. for industry. Available: http://www.​fda.​gov/​downloads/​drugs/​guid​ ance​comp​lian​cere​gula​tory​info​rmation/​guidances/​ucm291128.​pdf Acknowledgements Thanks to Monica Gheorghe from ESMO for supporting [Accessed Sep 2018]. the project. 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