Webinar as an Informational Resource on Trastuzumab Biosimilars: Planning, Promotion, Execution, and Evaluation

Abstract

Despite the incorporation of trastuzumab biosimilars (to treat HER2-positive breast cancer) in clinical practice guidelines, gaps remain such as patient and clinician education. We hosted a webinar comprised of a panel of biosimilars experts, oncologists, pharmacist, infusion nurse, and a patient advocate. The outcomes of the webinar include audience responses to pre- and post-webinar questionnaires, educational benefits, real-time opportunities to ask questions, and a recording. Education needs to be tailored to the needs of both, patients and clinicians.

Keywords:

• Biosimilars
• trastuzumab
• breast cancer
• webinar

In the last decade, the Federal Drug Administration (FDA) has approved five trastuzumab biosimilars for treating early-stage and metastatic HER2-positive breast cancer, as alternatives to trastuzumab biologic. The FDA defines biosimilars as highly similar (but not identical) to the reference product in terms of safety, efficacy, and quality (1). A phase 3 and extension study conducted with 347 patients with HER2-positive breast cancer, found that 3-year event-free survival was higher for a trastuzumab biosimilar compared to reference medication, and cardiotoxicity was similar (2). Studies highlight the importance of monitoring critical quality attributes to ensure consistent quality of trastuzumab biosimilars, given their potential to improve accessibility to trastuzumab therapy with no compromise to safety and efficacy (3).

American Society of Clinical Oncology has been proactive in keeping information up-to-date and creating opportunities and resources for clinician-facing education on biosimilars (4,5). A Continuing Medical Education (CME)-certified educational initiative for cancer care clinicians, comprised of 3 live meetings (in conjunction with ASCO meetings) and an online course, was developed and implemented in 2017–2018. Metrics showed that the initiative improved clinical knowledge, awareness, and confidence regarding biosimilars. However, the authors suggest that more education is needed in this dynamic domain (6).

In 2020, ASCO published updated guidelines for the selection of optimal adjuvant chemotherapy for breast cancer, highlighting that clinicians may offer any approved and available formulations of trastuzumab, including biosimilars (7). A 2022 ASCO expert panel update on the use of biosimilars in oncology highlights the remaining gaps including variance in use and suggests there is room for improvement in the uptake of these lower-cost alternatives (8). This is the case despite active efforts to address safety concerns by ensuring a rigorous regulatory approval process by the FDA along with thorough preclinical and clinical evaluation (9).

Along with continued clinician-facing education, patient knowledge and comprehension regarding biosimilars have been an area that has received little attention. Survey research suggests that non-medical switching of patients to trastuzumab biosimilars has contributed to patient distress and highlighted knowledge gaps. Additionally, patients and oncologists diverge in their perspectives about switching (10). These findings highlight the need for patient-facing education, as well as examination and improvement of patient-clinician communication on this topic.

Although there has been a shift to engage patients in conversations regarding solutions that pertain to them, historically, patient perspectives and lived experiences have been left out (11). Triangulating perspectives from all stakeholders in a problem space (12), especially for patients given they are directly impacted, is critical to appropriately address knowledge gaps, information needs, and mitigating avoidable distress. In other words, to inform solutions in care delivery that center on the patient, it is critical to include the experiences and perspectives of patients alongside the perspectives of clinicians (and other relevant roles).

As part of a project to develop an informational toolkit on trastuzumab biosimilars, we hosted a panel webinar to share consumable information, identify knowledge gaps, and elicit experiences from multiple perspectives. Our intended audience included patients and cancer care clinicians. The objective of the webinar was three-fold: to (1) provide up-to-date information on the science of trastuzumab biosimilars in a consumable manner; (2) represent informed perspectives, through targeted discussion, from multiple stakeholder roles, including a patient advocate, clinicians, and administrative decision makers on communication regarding trastuzumab biosimilars and treatment changes; (3) create a video informational resource, and (4) inform future work by identifying gaps in knowledge and outstanding questions.

Organization and planning

Our goal was to include multiple stakeholders (administrator, oncologist, pharmacist, infusion nurse, and patient advocate). One oncologist (Dr. Lustberg) and the patient advocate (Ms. Johnson) are members of the immediate project team. All additional manuscript authors took active roles in planning, promoting, and executing the webinar. We recruited additional panel participants through our professional networks, initially reaching out over email, followed by scheduling a phone conversation to answer questions. Dr. Lyman and Dr. Harvey have both administrative experience by serving on the American Society of Clinical Oncology (ASCO) Task Force on Biosimilars and clinical experience associated with trastuzumab biosimilars. An infusion nurse (Ms. Valero) has extensive clinical experience working with underserved patients receiving chemotherapy (including trastuzumab) infusions at the University of Illinois Hospital. Participants outside of the immediate project team received an honorarium upon the completion of the webinar. The resulting panel composition is represented in Table 1.

Table 1. Panel composition – names, affiliations, role on the panel, and biographies.

Name Affiliation Role on Panel	Biography
Lustberg, Maryam, MD, Medical oncologist Yale University, New Haven, CT Facilitator	She currently serves as Chief of Breast Oncology and Director of the Breast Center at Yale Cancer Center in New Haven Connecticut. She is the co-chair of Symptom Intervention for Alliance Clinical Trials and is the incoming President of MASCC, an international organization devoted to improving cancer supportive care throughout the globe. Clinically she treats men and women with all stages of breast cancer with a focus on personalizing all aspects of cancer care.
Lyman, Gary, MD Medical oncologist, biosimilars expert Fred Hutchinson Cancer Research Center, Seattle, WA Speaker & panelist	He is a Professor in the Public Health Sciences and Clinical Research Divisions at the Fred Hutchinson Cancer Research Center and Professor of Medicine at the University of Washington in Seattle. He is a Medical Oncologist with a focus on breast cancer and cancer supportive care and has a background in biostatistics and research methodology. He has written and spoken extensively on biosimilars in oncology and serves on the ASCO Task Force on Biosimilars.
Harvey, R. Donald, PharmD Pharmacist Emory University School of Medicine, Atlanta, GA Panelist	He is an oncology pharmacist and Professor in the Department of Hematology and Medical Oncology and Pharmacology at Emory University School of Medicine. He also serves as Medical Director of Winship's Clinical Trials Office and leads the Phase I clinical trials section.
Valero, Leeann Infusion nurse University of Illinois Hospital, Chicago, IL Panelist	She is an infusion nurse at UI Health. She has worked there for 6 years. She has been a nurse for 12 years, all focused in oncology.
Johnson, Sheila Patient Advocate Belleville, IL Panelist	She is a 25-Year Air Force Veteran and a 11 Year MBC patient. Sheila's extraordinary platform and advocacy is to help end racial disparities in the Black community and to enroll more Black patients into clinical trials.

We identified the following learning objectives for the webinar: (1) improve understanding of trastuzumab biosimilars, including efficacy and safety; (2) gain an awareness of existing knowledge gaps from multiple perspectives; (3) appreciate the value of lived experiences of patient-clinician communication regarding cancer treatment changes. We also developed targeted questions to be directed to the panel and proposed which panelist might be in a position to respond to each. These questions were informed by knowledge gaps identified in datasets comprised of patient and oncologist surveys (10,13). We shared an agenda (including timing) along with the predetermined questions with panelists several days prior to the webinar. We allotted 60 minutes for discussion to engage panelists and to elicit audience questions.

Promotion

The project team developed a promotional flyer (Figure 1) for the webinar to be shared on social media. We made a conscious decision to differentiate the flyer from the standard template of the webinar host university, the University of Illinois at Chicago. The flyer design included a project logo and an overview. The University of Illinois Cancer Center (UICC) provided support by promoting the webinar formally through email and on their website (alongside other UICC events). The project team posted the flyer repeatedly and daily on social media (Twitter), using the hashtag #bcsm.

Figure 1. Event flyer.

Execution

The webinar took place on Wednesday, October 20, 2021, 11 AM – 12:30 PM CST on Zoom. We had 15 audience members, which is 39% (15/38) of all registrants. The event began with an introduction by Dr. Papautsky (first author of this paper), followed by Dr. Lyman’s talk, and a discussion that included predetermined and audience questions. Figures 2 and 3 represent the sequence of activities during the webinar and a screenshot of the panelists and one of Dr. Lyman’s presentation slides, respectively. Dr. Papautsky assured adherence to the timing in the agenda. She monitored chat and texted audience questions to Dr. Lustberg. In Table 2, we provided the questions (along with the source) and the corresponding responses by the panelists. At the end of the panel, all panelists provided final thoughts for steps forward:

Figure 2. The sequence of activities during the webinar.

Figure 3. Screenshot of the panelists and one of Dr. Lyman’s presentation slides.

Table 2. Discussion questions and responses.

Questions	Responses
It appears that a potential challenge in talking about trastuzumab biosimilars with patients, but even between clinicians, is terminology. To what extent do you think it is important to be using accurate terminology to refer to trastuzumab biosimilars by either that term or by their brand names (as opposed to continuing to use the term ‘Herceptin’ to refer to them, or ‘generic,’ or ‘generic-like,’ etc.)? (source: predetermined question)	Dr. Lyman: “It is impossible…to remember the names of these four-letter suffixes that occur and relate them to specific agents.” “Even if the FDA conventions are important and necessary for monitoring.” “As physicians we have been taught…to focus on the brand name.” “...looking for some four letter referent that is more meaningful.” Dr. Harvey: “It is most helpful to focus on the generic name of the drug.” “Herceptin will always be in the mindset of individuals who are prescribing, using, and receiving these drugs.” “I do believe using the term trastuzumab is probably the best way forward.” “Even though we treat them like generics, how we communicate the generic versus similarity of the biosimilars is critical between clinicians and patients.” Dr. Lyman: Biosimilars are complicated and it takes a longer conversation to flesh them out. “These issues of extrapolation, immunogenicity, interchangeability, these are things we didn’t talk a whole lot about in the past…it is important, at some level…to reassure them, here are the steps they have gone through…it takes up a lengthy conversation sometimes, but it’s important.”
What would you say to someone who might suggest that patients don’t have anything to worry about (because safety and efficacy are comparable) and therefore there is no need to notify them? The idea that ‘we don’t want to worry patients unnecessarily.’ What about the idea that notifying them might put an additional strain on clinicians, with patients getting distressed and asking additional questions? (source: predetermined question)	Ms. Johnson: “Becoming a patient advocate, I learned more about it…I didn’t know about biosimilars so I had to literally research it myself and see oh, this is what a biosimilar is.” “Even the slightest change in your healthcare, you should be able to ask your doctor about it or your doctor should be able to talk to you.” “Communication should always be there.” “25% of Black patients aren’t even offered Herceptin, so what if they could get on a biosimilar at a cheaper price, are they even introduced to biosimilars?…I think it’s important that we continue the conversation.”
Are these rare experiences that the side effect profiles can be different among biosimilars? (source: audience member question)	Dr. Harvey: “From a pharmacy and pharmacological perspective, [Biosimilars] are some of the most targeted drugs we have.” “These are much more specific than other drugs we use, like cytotoxic chemotherapy.” “If you feel like, as a patient, [side effects] are due to something that is new, something that has changed, it’s always good to chat with your health care providers to talk about...oh I got this and I felt this way and you then need to contextualize that with everything else that is happening in the care of a given cancer patient, including other drugs and their timelines.” “Side effects are important, we certainly want to make sure we help patients manage them, think through them, and prevent them, ideally.” Dr. Lyman: Its important for patients to communicate with their providers and there are no dumb questions.” “If you don’t tell the clinician, then the clinician can’t appraise it and then report it if it seems appropriate.” “There is a formal FDA process for tracking emergent symptom trends.” “These are large proteins and they may cause allergic responses, so patients are monitored. … look to see if symptoms affect efficacy, note and report when certain biosimilars seem more effective.” “Communication from the patient to the clinician and from the clinician to the either the FDA or the pharmacy and therapeutics committee - these are really important avenues to keep open and to use regularly.”
As an oncology infusion nursing leader, you’re often in the front lines where sometimes you are fielding a lot of questions from patients about trastuzumab biosimilars, and I would love to hear your perspective in terms of what you have experienced about how we can improve on this project in terms of communication and patient care (source: audience member question).	Ms. Valero: “I think what’s really important is that [biosimilar education] starts from the beginning.” “When [providers] are consenting [patients]. I think its important to not use the word Herceptin…and to say ‘the trastuzumab’ or ‘the trastuzumab biosimilars’ and give them that opportunity to ask those questions, because that’s what informed consent is, right? They should have that ability to ask those questions. Our physicians and providers should be answering that.” “[When] our pharmacists and their students and residents do education…talk to the patients about what they are getting, and the side effects…say, OK, the side effects - are they similar or different than the original biologic?” “I, as the nurse…I make sure I am available to answer those questions…at every point, make sure everyone is involved in being able to provide education to the patients if they ever have any questions.” “Starting from the beginning, and letting them be aware that this is what they are getting, I think is the most important.” “Clinicians should be educated in how to give consent and field those questions. Everyone should be involved in answering and asking questions, but it needs to start well (with clarity, etc).” Dr. Lyman: Patients underreport because otherwise doctors may stop their treatment, or perhaps just don’t want to bother the doctor. Nurses may figure it out before doctors. Ms. Johnson: Patients may be afraid that doctors will take them off medications if they report symptoms, but patients should report side effects because the doctors are there to help work through and manage those symptoms. Suggests to provide patients the fact sheet.
Who makes the decisions about the switch to the biosimilar? Do patients have a say? (source: audience question)	Dr. Lyman: “We like to think the decision was made after a discussion between the clinician and the patient about what’s best for them and appropriate. The reality is it’s often reimbursement options, and negotiated contracts between either companies and institutions and practices, or between the payer (who defines preferred agents), and often there’s some penalty if you don’t use a preferred agent, and that penalty increasingly falls on the patients…What has concerned clinicians is that it’s really cost, not care, which is driving these decisions and we like to think it’s just the opposite.” “It really is complicated, and unfortunately, patients again are caught in the middle of all this. In the end…we do hope that the savings to institutions and insurers get passed on to patients….It’s too early to know for most of the biosimilars in oncology.” “The more competitors there are…the lower the price.” Paraphrase: “Doctors (should be) should be focusing on clinical reasons, not economic reasons (to use biosimilars).” Dr. Harvey: Agrees with Dr. Lyman and reiterates that competition will drive prices down. There is some confusion when multiple products are allowed by insurance, the problem of supply and storage. Would like lower cost medications, which would benefit pharmacists too.
What are ways we can improve on this process? (source: Dr. Lustberg question)	Ms. Valero: Has seen situations in which patients were on Herceptin and then the insurance switched. “The second they tell me, personally, ‘I didn’t know I switched,’ then I stop right there. I’m not going to just continue hanging it. I’m going to talk to the doctor or talk to our nurse practitioner and say ’hey, this patient was never made aware, so they have questions. Can you take the time to speak with this patient?’ And they don’t always have time, but giving the patient reassurance and time to process the switch is good, asking for questions. Insurance is a big thing and a lot of paperwork.”
Question addressed to Drs. Lyman and Harvey: “When the patient switches like that, are you reconsenting them, or is it part of your consent that biosimilars are an OK change without having that discussion or having them pre-sign consent?”	Dr. Lyman: Varies from practice to practice. The emphasis should be more on the communications (to mitigate surprise). Biosimilars are heading toward interchangeability, though skeptical about it achieving it due to the expense of the trials. Clinicians and insurance are treating them as interchangeable anyway (so there is low incentive to fund those trials). Dr. Harvey: His clinic does not reconsent, but agrees the area and the terminology is cloudy, using the analogy and lack of reconsenting for generics. But the consensus medically, is that there are not meaningful clinical differences between them. There is benefit to biosimilar use in 3rd world countries due to cost profile. Dr. Lyman: Agrees that biosimilars are good for accessibility.
Is it really safe if I started on Herceptin, and switched back to one biosimilar, and then to another? And what I’m hearing from you experts is that this is safe, ok to do, is that correct?”	Dr. Harvey: “A pharmacist at the point of dispensing can say: ’If you have brand name Novadex, and we have generic Tamoxifin on the shelf, we’re going to give you generic Tamoxifen,’ and we can do that legally, because states tend to have generic substitution laws that are effectively interchangeable laws.” “Interchangeability was something the FDA tried to kind of make that process the same.” Thinks interchangeability will become less important over time as this switching happens organically.

Note: Content is comprised of direct quotes, as well as summary statements.

• “…sharing what questions patients should ask, patients sharing their experience with other patients.” (Ms. Johnson)

• “For nursing, I think it’s important to keep educating ourselves on the information, and just keep being open to sharing that with patients…Say to patients: ’Just keep asking questions.’” (Ms. Valero)

• “Use your pharmacist…get them out of their room, engage them, everyone - doctors, nurses, patients.” (Dr. Harvey)

• “Knowledge is power, and knowledge requires communication. If the doctor’s not hearing from you about a problem, and then conveying that to appropriate channels, then we don’t learn and we don’t improve.” “There is no bad question and no complaint that shouldn’t be considered. No matter how much you think it isn’t a problem, share it, and, you know, discuss it.” (Dr. Lyman)

Evaluation

We developed pre- and post-webinar evaluation questions for the audience to characterize attendee background and their knowledge gaps and to identify which knowledge gaps remain, as a function of potentially missing content in the webinar or content that needs to be presented in a more comprehendible manner. We used quick response (QR) codes presented on a Microsoft Powerpoint slide to share a link to the pre- and post- webinar questions hosted on Poll Everywhere (polleverywhere.com), an online audience response system. Specifically, the QR codes were shared at the beginning and at the end of the webinar. Dr. Papautsky reminded the audience verbally and over chat to complete the questions.

Pre- and Post-Webinar evaluation results

Approximately 15 participants attended the webinar. Not all participants responded to the pre- and post-webinar questions. Of 9 respondents, 5 were patients, and the rest were caregivers, pharmacist, oncologists, and nurses. Eight respondents generated 17 adjectives associated with trastuzumab biosimilars, with the most frequently (twice each) used being: breast cancer, effective, and less expensive. See Figure 4 for a word cloud comprised of the elicited adjectives. Six of 9 respondents rated their knowledge as either poor or fair and wanted to learn about side effects, efficacy, and whether biosimilars were equal to biologics. We received the below responses to the question What do you hope to learn from this webinar and why?. Please note that the responses are presented as they were provided including potential misspelling and grammatical issues.

Figure 4. Word cloud comprised of elicited adjectives regarding trastuzumab biosimilars.

• “My insurance company wants me to switch to a biosimilar after 5 years on herceptin. I am NED on first line treatment stage 4 triple positive breast cancer and I worry about making any changes. Are they truely equal???”

• “The differences in this medication VS Herceptin, and what feedback has been given about side effects”

• “Are they an option for me after being on Herceptin for 4 years?”

• “Patient perspectives on use”

• “Efficacy-data. Better-communication”

• “How and when biosimilars are being used? Is this a choice made by patients, providers, healthcare organizations, or insurance companies?”

• “I learn that the change was safe and that I need to watch for side effects and talk to my oncologist if I have any side effects. It also empowers me to talk to my team and encourage them to have a more open conversation about biosimilars and not leading with an insurance change but that they are confidence in the switch.”

Only 3 individuals responded to the post-webinar questions. All reported that the webinar was easy to understand, with 1 highlighting that the differences between biologics and biosimilars are “over my head” and one wants to hear more about regulation and cost. All rated content and discussion as either excellent or good. The following statements reflect a remaining gap: “Still not 100% certain who has the authority/responsibility to choose a biosimilar over a biologic…” and a concern “I did find it disheartening that co-pays would not be helped with a biosimilar.” One respondent shared the following statement: “Great program! Very informative – engaging and interesting panelists.”

Takeaways

The webinar resulted in a lively discussion with no shortage of questions and responses, as well as received positive feedback from the audience and participants. In addition, through high visibility promotion by the project team, panelists, and their networks, along with UICC, achieved a large reach of exposure to the presence of a conversation on this topic. The promotional flyer posted on Twitter by Dr. Papautsky on September 28, 2021 (approximately 1 month prior to the event) achieved 12,005 impressions, 195 engagements, and 21 detail expands (according to Tweet Analytics). Based on the panel discussion, we have identified the following takeaways to inform the next steps in research and clinical practice associated with trastuzumab biosimilars (and perhaps beyond).

• People have questions. Questions are not limited to patients, but clinicians as well. Panelists reported the need for continued conversation regarding biosimilars and the need to engage patients in that conversation.

• This healthcare topic (and all topics) should engage all stakeholders, including patients and caregivers to account for lived experiences. Without engaging patients, challenges and issues may remain invisible and therefore, unaddressed.

• Trastuzumab biosimilars have many advantages, but a number of knowledge gaps and misunderstandings exist. These gaps need dedicated attention through multi-stakeholder conversations, educational initiatives, and research (to elicit and charaterize barriers). Such efforts can form the basis for informing effective promotion and uptake of trastuzumab biosimilars, including mitigating avoidable patient distress.

• There is a need for human-centered approaches for effective trastuzumab biosimilars resource design and dissemination that accounts for underserved populations.

Implications for managed care pharmacies

We identified several implications including the importance of: (1) ensuring comprehensive drug utilization reviews that account for patient experience of switching and side effects to inform prescriber recommendations; (2) promoting pharmacists as resources to patients (and clinicians) when faced with novel drug choices, (3) facilitating efficient and effective prior authorization to switch back to reference drug as needed, and (4) highlighting the need for culturally-sensitive patient-pharmacist consultations that are informative and effective in addressing patient questions.

Conclusion

Finally, the advantages of conducting an informational webinar are multi-fold. In addition to the real-time educational benefits and opportunities to ask questions of experts live, the recorded webinar serves as a resource that can be disseminated in service of future educational opportunities in complement other resources. The webinar is temporarily hosted on youtube.com on a UIC College of Applied Health Sciences (an affiliation of Dr. Papautsky) unlisted channel with 180 subscribers. As part of a poster on trastuzumab biosimilar we presented at the 2021 San Antonio Breast Cancer Symposium (10), we included a QR code to the webinar that yielded 7 visits. We plan to include the webinar recording as part of the informational toolkit on trastuzumab biosimilars.

Declaration of interest

Dr. Lyman reports grants from Amgen, personal fees from Sandoz, personal fees from G1 Therapeutics, personal fees from BeyondSpring, personal fees from ER Squibb, personal fees from Merck, personal fees from Jazz Pharma, personal fees from TEVA, personal fees from Samsung, personal fees from Fresenius Kabi, personal fees from Partners Healthcare, outside the submitted work. The remaining authors report no conflicts of interest.

Acknowledgements

We are thankful to Sheridan Chaney, Director of Marketing and Communications for the University of Illinois Cancer Center for facilitating dissemination and promotion. We are grateful to numerous colleagues, patient advocates, community members, and friends who helped to promote this event.

Additional information

Funding

This effort is funded by the National Comprehensive Cancer Network (NCCN) and Pfizer Global Medical Grants Adoption of Biosimilars in Oncology (Grant G1740 - Pfizer Inc).