Advances in the Multidisciplinary Management of Hepatocellular Carcinoma: Strategies for Incorporating Emerging Immunotherapy Treatment Options

Transcription

1 Advances in the Multidisciplinary Management of Hepatocellular Carcinoma: Strategies for Incorporating Emerging Immunotherapy Treatment Options Interim Outcomes Report Merck & Co., Inc. Grant ID: AAN

2 Overview Activity Description: Expert faculty Richard Finn, MD, discusses treatment options and strategies in a case-based approach for two patients who have failed conventional therapies and may be candidates for immunotherapy. The activity features an online virtual patient platform that affords clinicians an opportunity to absorb relevant clinical and evidence-based information. Launch Date: March 30, 2018 Expiration Date: March 30, 2019 Credit: 0.50 AMA PRA Category 1 Credits TM Sponsored by: The Academy for Continued Healthcare Learning (ACHL) Supported by: An educational grant from Merck & Co., Inc. Intended Audience: This activity is intended for physicians (oncologists, interventional radiologists, hepatologists) and other clinicians who care for patients with hepatocellular carcinoma (HCC). Activity link-achl Site: Activity link-mycme Site: Outcomes Methodology: Activity-related changes in clinician knowledge, competence, and practices were evaluated by using Level 5 outcomes to determine whether the educational objectives of the activity were achieved.

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4 Executive Summary: Levels 1-2 Participation 539 Participants; 142 Certificates ( participant guarantee), data as of 8/7/18 Practicing Type 50% Physicians/PA s; 35% RNs/NPs; 15% Other Participant Satisfaction Objectivity and balance rated as good/excellent by 96% of learners Learning Objectives 98% of learners strongly agree or agree that all learning objectives were met, with an average rating of 3.44/4.0 Faculty Dr. Finn was highly rated by learners at 3.46/4.0

5 Executive Summary: Levels % indicated participation in the activity will impact their patient outcomes 63% of learners indicated that their competence increased after participation in this activity Changes made from this activity will impact 577 to more than 1,464 patients each month Cost, lack of opportunity (patients), and lack of experience were reported as the most common barriers to implementing changes in practice Following the activity, learners demonstrated increased knowledge and competence about the use of tyrosine kinase inhibitors as well as immunotherapy treatment options in the management of HCC

6 Level 1: Participation Participants Certificates Participation by Clinician Type 15% 20% Physician Assistant Physician Nurse Practitioner Nurse Other 22% Participation by Specialty Family Medicine/General Practice Hematology/Oncology Internal Medicine Oncology Surgery Cardiology Gastroenterology/Proctology Emergency Medicine Other 11% 12% 11% 4% 5% 6% 4% 30% 13% 17% 30%

7 Level 2: Learning Objectives Please rate the following objectives to indicate if you are better able to: Differentiate the mechanisms of action and scientific rationale of currently available systemic therapies with the use of immunotherapy approaches in advanced HCC Discuss the role of new and emerging immunotherapies in current treatment paradigms for advanced HCC Review the efficacy, safety and tolerability of emerging agents for advanced HCC and the management of immune-related adverse events Evaluate the evolving immunotherapeutic research landscape, including ongoing studies in earlier stages of disease as well as personalized and locoregional therapies Analysis of Respondents Rating scale: 4=Strongly Agree; 1=Strongly Disagree % of learners strongly agree or agree that all learning objectives were met, with an average rating of N=133

8 Level 2: Satisfaction Overall Evaluation Analysis of Respondents Rating scale: 4=Excellent; 1=Poor Scientific rigor 3.42 Effectiveness of teaching method used 3.33 Appropriateness and effectiveness of active learning strategies 3.31 Time allotted for presentation of information 3.36 All aspects of the activity were highly rated with an average of 3.36/ % of learners would recommend this activity to a colleague. N=133

9 Level 2: Faculty Evaluation Please rate the faculty on the criteria listed Rating scale: 4=Excellent; 1=Poor Ability to effectively convey the subject matter Ability to present scientifically rigorous information Expertise on subject matter Richard Finn, MD The faculty was rated good or excellent across all areas by 90% of learners, with an average rating of 3.46/4.0 N=133

10 Objectivity & Balance Did you perceive any bias? Rating of objectivity & balance 60% 50% 47% 50% 96% 40% 30% 20% 4% Yes No 10% 0% 3% 0% Excellent Good Fair Poor N=133 Activity was perceived as objective, balanced and non-biased.

11 Levels 3-4: Pretest vs. Posttest Overview of Correct Responses* Topic REFLECT Study: TKI Use in Advanced HCC KEYNOTE 224 Study: Immunotherapy Use in Advanced HCC % Change Physicians Pre=54 Post=44 % Change NPs/PAs Pre=96 Post=79 % Change Other 8% 11% -64% 28% 0% -49% Pre=25 Post=14 Physician participants demonstrated improved knowledge and competence in both topics, while performance for immunotherapy use did not improve for other healthcare providers. Additional expanded education for use of both tyrosine kinase inhibitors and immunotherapy agents in a first- and secondline setting for advanced HCC would be beneficial to improve more dramatic clinical knowledge and awareness, particularly for non-physician health care providers. *first attempt responses

12 Levels 3-4: Pretest vs. Posttest REFLECT Study: TKI Use in Advanced HCC For a patient with advanced, unresectable HCC with no prior history of systematic therapy, which of the following statements regarding the use of a multi-kinase inhibitor in a frontline setting is correct based on results of the REFLECT trial? A. The multi-kinase inhibitor lenvatinib is inferior to sorafenib in both overall survival and progression-free survival. B. The overall reported adverse events of both lenvatinib and sorafenib are equivalent C. The multi-kinase inhibitor lenvatinib is not inferior to sorafenib in overall survival but is superior in progression-free survival and objective response rate D. Sorafenib showed a greater maximum change in tumor size than lenvatinib 100% 80% 60% 40% 20% 0% Physicians Post=44 48% 52% 22% 18% 19% 23% 11% 7% A B C D Pre=54 100% 80% 60% 40% 20% 0% NPs/PAs Post=79 35% 39% 27% 22% 20% 24% 19% 14% A B C D Pre=96 100% 80% 60% 40% 20% 0% Other Post=14 50% 40% 36% 29% 12% 14% 12% 7% A B C D Pre=25 NPs/PAs demonstrated the greatest knowledge improvement on this clinical subtopic, increasing knowledge performance by 11% versus pre-test. As anticipated, physicians demonstrated a relatively high pre-test knowledge; after the educational activity, they exhibited a 8% increased performance.

13 Levels 3-4: Pretest vs. Posttest KEYNOTE 224 Study: Immunotherapy Use in Advanced HCC When used as second-line immunotherapy treatment option, which of the following checkpoint inhibitors has been shown in the KEYNOTE 224 study to demonstrate a significant change in tumor lesion size in both HBV and HVC patients with advanced HCC? A. Nivolumab B. Pembrolizumab C. Durvalumab D. Avelumab 100% 80% 60% 40% 20% 0% Physicians Post=44 50% 35% 39% 32% 22% 18% 4% 0% A B C D Pre=54 100% 80% 60% 40% 20% 0% NPs/PAs Post=79 43% 43% 35% 30% 19% 12% 10% 8% A B C D Pre=96 Other 100% 80% 60% 40% 20% 0% Post=14 56% 36% 29% 29% 24% 16% 4% 7% A B C D Pre=25 Physicians showed the greatest knowledge improvement on this topic, increasing knowledge performance by 28% versus pre-test. NPs/PAs still demonstrated relatively high pretest performance levels that remained unchanged. Given the new and novel use of immunotherapy agents within this disease state, it is evident that further education can help to increase awareness and knowledge of these emerging agents as part of new treatment paradigms that in turn can translate to better clinical understanding and utilization for appropriate patients.

14 Level 4: Practice Change Create/revise treatment protocols, policies, and/or procedures 26% Change the management and/or treatment of my patients 37% Other changes 10% This activity validated my current practice; no changes will be made 44% 0% 10% 20% 30% 40% 50% 56% of learners will change their practice! N=133; multiple responses allowed; other changes found in appendix

15 Polling Question Patient Case 1 If or when approved, how confident are you in using immunotherapies in clinical practice for advanced HCC patients in a frontline setting? Very confident Moderately confident Somewhat confident Not at all confident 11% 22% 26% 41% N=54 0% 10% 20% 30% 40% 50% 60% Looking beyond current frontline treatments for advanced HCC, and given acceptable efficacy, safety and tolerability, how likely are you to employ immunotherapies for HCC treatment if or when approved? Very likely 35% N=26 Moderately likely Somewhat likely Not at all likely 15% 23% 27% 0% 10% 20% 30% 40% 50% 60% 63% of learners indicated low confidence in immunotherapy agents while 48% indicated low likelihood of use in a firstline setting. Given the practice-changing impact that immunotherapy will likely yield in the treatment of advanced HCC disease, it is imperative to increase depth and breadth of education across clinician types to ensure better patient outcomes through immunotherapies and to promote greater confidence and likeliness of use in the clinic among all health care providers.

16 Polling Question Patient Case 2 How suitable do you consider this patient to treat with an immunotherapy such as a checkpoint inhibitor as second-line treatment? Very suitable Moderately suitable Somewhat suitable Not at all suitable 4% 23% 0% 10% 20% 30% 40% 50% 60% 33% 40% N=52 In considering both efficacy and safety, how likely are you to use an approved immunotherapy such as a checkpoint inhibitor as second-line treatment on this patient? Very likely 30% N=20 25% 30% 15% Moderately likely Somewhat likely Not at all likely 0% 10% 20% 30% 40% 50% 60% While 63% of learners consider an advanced HCC patient suitable for treatment with a checkpoint inhibitor in a secondline setting, 55% indicated likeliness to utilize it for treatment. Additional education emphasizing the safety and tolerability of these agents is imperative to ensure routine and robust clinical utilization for appropriate patients.

17 Follow-up Survey Since completing the activity, how often have you utilized checkpoint inhibitors for second-line treatment of a patient with advanced HCC who has progressed post-sorafenib? Always 31% Very Often 53% Often 8% Not at all 8% 0% 10% 20% 30% 40% 50% 60% 84% of learners have always, or very often, utilized checkpoint inhibitors for second-line treatment of a patient with advanced HCC who has progressed post-sorafenib. N=13

18 Follow-up Survey Since completing the activity, how confident are you in selecting immunotherapy for your patients with HCC in the second-line setting and if/when approved in the first-line setting? Extremely confident 16% Very confident 38% Somewhat confident 46% Not very confident 0% Not confident at all 0% 0% 10% 20% 30% 40% 50% 60% N=13 After participating in this activity, 54% of learners indicate that they are extremely or very confident in selecting immunotherapy for their patients with HCC in the second-line setting and if/when approved in the first-line setting. Additional education elaborating on the most recent data released from clinical trials can help to bolster and enthuse greater confidence for immunotherapy agents.

19 Follow-up Survey Pembrolizumab, an immunotherapy under investigation for HCC in the first-line setting and approved for use in the second-line setting, is an antibody against: Programmed cell death protein 1 (PD-1) 15% Programmed cell death-ligand 1 (PD-L1) 31% Cytotoxic T-lymphocyte associated antigent 4 (CTLA-4) 46% Cluster of differentiation 152 (CD152) 8% 0% 10% 20% 30% 40% 50% 60% N=13 Although survey responses were small, greater awareness of pembrolizumab as a PD-1 blocker is needed, particularly as it offers the prospect to transform treatment of advanced disease in both treatment setting.

20 Follow-up Survey In the time since your participation in this activity, where do you feel immunotherapy will have a compelling clinical impact in the treatment of advanced HCC? In both first- and second- line therapy 55% As a first-line therapy 15% As a second-line therapy 15% I haven't implemented immunotherapy into my practices 15% 0% 10% 20% 30% 40% 50% 60% 55% of learners indicated that they feel immunotherapy will have a compelling clinical impact in both first and second-line therapy. Further education can help shift such perspective to even more positive levels in line with expectations arising from promising clinical trial data. N=13

21 Follow-up Survey In the REFLECT clinical trial, the multi-kinase inhibitor lenvatinib showed superiority in progression-free survival and objective response rate over sorafenib in patients with advanced, unresectable HCC with no prior history of systematic therapy. How likely are you to use lenvatinib in a frontline setting for such patients? Always Very often 50% 50% Often Not at all 0% 0% 0% 10% 20% 30% 40% 50% 60% Following this educational activity, 100% of respondents are willing to use the TKI lenvatinib in a frontline setting for advanced HCC patients. N=4

22 Level 5: Follow-up Survey Please list 1-2 ways you have changed your practice as a result of attending this activity: Discussing immunotherapy options with my colleagues and patients Feeling better informed about this medication, thank you! Discussed more ways to increase patient compliance Following this educational activity, positive feedback regarding immunotherapy use in HCC was observed. N=4

23 Activity Impact Self-reported activity impact Yes No No change Increase knowledge 81% 6% 13% Increase competence 63% 11% 26% Improve performance 56% 12% 32% Improve patient outcomes 53% 17% 30% This activity was highly effective, with 56% of attendees indicating participation in this activity will improve their performance. N=133; see comments in appendix

24 Patient Care Impact Number of patients affected by these changes each month: % 6% 2% >20 55% 32% Changes will impact 577 to more than 1,464 patients each month. This assumes data in chart above is representative of all healthcare professionals in attendance (539), who indicated they would change their practice as a result of their participation in this activity (56%).

25 Barriers to Planned Change Cost 29% Patient compliance issues Lack of time to assess/counsel patients 8% 9% Lack of opportunity (patients) 20% Lack of experience 23% Reimbursement/insurance issues 13% Lack of administrative support 5% Lack of consensus or professional guidelines Lack of resources (equipment) Other 2% 2% 11% No barriers 22% 0% 5% 10% 15% 20% 25% 30% 35% Participants indicated cost (29%) as most common barrier to implementing changes in their practice, followed by lack of experience (23%) and lack of opportunity (patients) (20%). Of those who identified barriers, 44% will attempt to address the perceived barrier(s) in order to affect change. N=133; multiple responses allowed

26 Topics of Interest Review of treatment-related adverse events of immunotherapies and strategies for their management 43% Review of new and emerging treatment options in the treatment of advanced HCC Review of trial data on the use of immunotherapies in a frontline setting 35% 38% Workshop on developing treatment strategies for patients with advanced HCC 17% 0% 20% 40% 60% Review of treatment-related adverse events of immunotherapies and strategies for their management was rated with highest interest for future education. N=133; multiple responses allowed

27 Contact Information Greg Paladino VP, Education Development Academy for Continued Healthcare Learning (ACHL) E: P: ext. 200 C:

28 Appendix

29 Levels 3-4: Activity Impact Self-reported increase in knowledge Better understanding of treatment options for HCC Conservative approach still a factor Emerging data on check-point inhibitors in the treatment of HCC Have had little previous experience with treatment strategies I have gained more knowledge in the realm of hepatocellular carcinomas Identifying benefits of drug in HCC setting This exercise has taught how better to take better care of my Hepatitis C patients along with my Hepatologist Specialists Strengthened my knowledge on neoadjuvent treatment The emerging role of immunotherapy for HCC Valuable assessment Good quality Introduced trials that I was not familiar with Better understanding of the drugs used Overall survival rate New medication, treatment dimension Knowledge regarding advance therapy that is available Improved knowledge on OS, PFS, and SE Self-reported increase in competence All news about management of this lethal condition is of interest CME is the teacher Data on OS and PFS More knowledge of drugs being studied First and second-line therapies As an older family Dr, I feel more comfortable talking with the patient and the liver specialist about my patient s condition! I learned about new trial of immunotherapy More in the treatment algorithm Plan future salvaged treatment options Treatment options New pharmacy info for me Better understanding of drug therapy in HCC All news about management of this lethal condition is of interest

30 Level 5: Activity Impact Self-reported increase in performance Better understanding of drugs and side effects Communication skills Consider immunotherapy clinical trial for patients Refer for treatment Therapeutic advantages It helps me to understand the Rxs of my oncology colleagues in the care of HCC patients I am a nurse who covers for five different oncology doctors with all different specialties. This was a good lesson to learn the multiple medications for alternate diagnoses Early therapy I will be able to discuss treatment options. l will be better able to understand the hepatologist treatment and better able to counsel my patient! Self-reported increase in patient outcomes Increase outcomes for patients More in the treatment armamentarium Increase OS for HCC patients Increased DFS I will be better able to interact with the patient and the hepatologist by understanding the guidelines from the hepatologist Providing better choices in the treatment of HCC They will improve and get better Treatment options It will make me a more effective partner with my oncology and radiation rx colleages to accomplish best outcomes