Cardio-Oncology: Can we make a difference?

Transcription

1 Cardio-Oncology: Can we make a difference? Daniel J Lenihan, MD Professor, Division of Cardiovascular Medicine Director, Clinical Research Vanderbilt University

2 Presenter Disclosure Information Global Cardio-Oncology Summit 2016 Vancouver BC Canada, I will not discuss off label use or investigational use in my presentation. I have financial relationships to disclose: Research support from: Acorda, Inc; Takeda, Inc. Consultant (modest): Roche, Amgen, Prothena, BMS

3 Significant reversibility of LV dysfunction with trastuzumab-related cardiac toxicity; Importantly, patients can continue trastuzumab treatment despite LV dysfunction Journal of Clinical Oncology 2005,23;p

4 What is Cardio- oncology? PubMed Chemotherapy Cardiotoxicity

5 Case study: Anti-VEGF therapy 60 y/o F, with HTN and DM, presents with metastatic renal cell cancer that led to L nephrectomy, radiation to pelvis and ribs, lung nodules (probable metastatic dz), and resection of R femur tumor with a femoral nail placed, who was started on sunitinib 2 months ago. MEDS: triamterene, losartan, sunitininb 37.5 mg, Zofran PE: BP 168/92, P88, wt 178#, R16 No JVD, lungs clear, loud S4, trace ankle edema Labs: Cr 1.1, TC 227, LDL 129, HDL 31, BNP 18, LVEF 55 with mild LVH 5 weeks after starting sunitinib she developed BP 216/112 and had therapy stopped

6 From: The Frequency and Severity of Cardiovascular Toxicity From Targeted Therapy in Advanced Renal Cell Carcinoma Patients JCHF. 2013;1(1): doi: /j.jchf Figure Legend: The Stanford Monitoring Algorithm for Targeted Therapies Cardiovascular monitoring algorithm for patients with renal cell carcinoma receiving targeted chemotherapy. BP = blood pressure; DBP = diastolic blood pressure; SBP = systolic blood pressure; other abbreviations as in Figure 1. Date of download: 5/31/2014 Copyright The American College of Cardiology. All rights reserved.

7 In Renal Cell Cancer, renin-angiotensin inhibitors are critical therapies R McKay et al, Clin Cancer Res Jun 1; 21(11):

8 RAS inhibitors seem to be very important R McKay et al, Clin Cancer Res Jun 1; 21(11):

9 Statins are helpful in renal cell cancer especially with anti-vegf directed therapy Statins: yes Statins: yes OS Anti-VEGF R McKay et al European Journal of Cancer 52 (2016)

10 So what happened with our patient? Control BP with what meds? stopped triamterene, continued losartan 50mg qd, used furosemide for edema, started carvedilol 25mg bid, amlodipine 10mg daily used hydralazine intermittently How do we follow this patient going forward? periodic BNP, rarely EF measured only for dyspnea Any other general recs? sodium restriction, exercise, lipid therapy, aspirin She has had no disease progression for almost 6 years!! and can walk ½ mile without stopping.

11 Case study: does cardiotoxicity mean the drug has to stop? 74 y/o F, with Multiple Myeloma initially in 2013 treated with velcade, adriamycin and decadron as well as s/p stem cell txp 2004, has relapsed disease. She was started on carfilzomib, pomalyst and decadron 12/2014. Prior hx of DM, HTN but told she had no cardiac problems On atenolol 50mg qd, Lisinopril 20mg qd, no aspirin or statin After 2 cycles of treatment developed NYHA class 3-4 symptoms Hematologist stopped therapy and was not going to treat further

12 PROTECT Study Design PROTECT is a prospective, non-randomized, open-label, supportive care, multiinstitutional study. 130 patients will be enrolled, who will be initiated with either (1) Bortezomibbased (BOR) or (2) Carfilzomib-based (CAR) therapy based on the hematologist s decision. Enrolled and initially treated with Bortezomib- based chemotherapy (N=65) 6 cycles of chemotherapy Patient with relapsed or refractory multiple myeloma screened for eligibility Enrolled and initially treated with Carfilzomib- based chemotherapy (N=65) 6 cycles of chemotherapy Sites: Vanderbilt University Medical Center University of Pennsylvania (UPenn) *Dana Farber at Harvard *University of Alabama *pending Ongoing monitoring for outcomes Ongoing monitoring for outcomes

13 Cardiac Events reported in PROTECT (CTCAE v4.0) Cardiac Event Acute coronary syndrome (ACS) which includes MI Arterial and/or venous thromboembolism # of events # of individuals BORtreated patients CARtreated patients 6 (13.9%) 6 (15.7%) 0 (0%) 6 (15.7%) 3 (6.9%) 3 (7.8%) 2 (5.2%) 1 (2.6%) Dyspnea 2 (4.6%) 2 (5.2%) 0 (0%) 2 (5.2%) Hypertension 13 (30.2%) 11 (28.9%) 2 (5.2%) 7 (18.4%) Symptomatic arrhythmia requiring treatment 2 (4.6%) 2 (5.2%) 0 (0%) 2 (5.2%) Symptomatic heart failure 16 (37.2%) 13 (34.2%) 3 (7.8%) 10 (26.3%) CTCAE grade grade 2 (n=3) grade 3 (n=3) grade 1 (n=1) grade 2 (n=1) grade 4 (n=1) grade 1 (n=1) grade 2 (n=1) grade 3 (n=11) grade 4 (n=2) grade 3 (n=1) grade 5 (n=1) grade 2 (n=6) grade 3 (n=10) Other (syncope) 1 (2.3%) 1 (2.6%) 0 (0%) 1 (2.6%) grade 2 (n=0) grade 3 (n=1) grade 1 (n=2) grade 2 (n=7) Total # of suspected cardiac (58.4%) 7 (18.4%) 29 (76.3%) grade 3 (n=25) events grade 4 (n=3) grade 5 (n=1) Chemotherapy doses were reduced for 4 patients due to cardiac events: CAR-treated patients (n=3) BOR-treated patient (n=1)

14 What happened with our second pa>ent? She was placed on spironolactone, Lasix, carvedilol, aspirin, crestor and Lisinopril. She walks daily, without symptoms of HF, and is in remission nearly 3 years later

15 Guidelines and Education

16 Pocket Guidelines also available!

17 Preven:on and monitoring of cardiac dysfunc:on in survivors of adult cancers: ASCO Clinical Prac:ce Guideline

18 American Society of Clinical Oncology: Clinical Prac*ce Guideline Click to edit Master >tle style Radia:on Oncology Family Medicine Epidemiology Oncology Cardiology Mul:- disciplinary collabora:on Pa:ent Rep. Exercise Physiology ACC Rep. AHA Rep. ASCO Rep.

19 Wri:ng Group Click to edit Master >tle style Saro Armenian Ana Barac Joseph Carver Louis S. Cons>ne Neelima Denduluri Susan Dent Pamela S. Douglas Jean- Bernard Durand Michael Ewer Carol Fabian Melissa Hudson Mariell Jessup Lee Jones Bonnie Ky Chris>na LaccheP Javid Moslehi Erica L. Mayer Kevin Oeffinger Katharine Ray Kathryn Ruddy Daniel Lenihan

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21 Can we identify training requirements? What is Cardio-Oncology? It is a clinically-based discipline focused on the cardiovascular health of cancer patients and cancer survivors Who is a cardio-oncologist? A health care provider who is focused on the prevention, early detection, management, and recovery of cardiovascular function potentially resulting from cancer therapies. Lenihan, D et al, JCF 2016:p

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24 Pa>ent Informa>on hup://be.macmillan.org.uk/be/p heart- health- and- cancer- treatment.aspx

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26 CML: Development of BCR-ABL Tyrosine Kinases Inhibitors Discovery of Ph chromosome 1-3 BCR-ABL kinase activity 1 Other therapeutic targets identified for development 1 t(9:22) 2, Tyrosine kinase inhibition 1 Resistance to BCR-ABL inhibitors identified 1 TKIs Have Expanded Treatment Options for Patients With CML 1. Wong et al. Annu Rev Immunol. 2004;22: ; 2. Nowell PC et al. J Clin Invest. 2007;117:2033-5; 3. Rowley JD et al. Nature. 1973;243:

27 CML: Common TKI-Related Adverse Events Myelosuppression Dermatologic AE Gastrointestinal AE Musculoskeletal symptoms Cardiovascular toxicity Metabolic and endocrine AE Hepatic and pancreatic AE Pulmonary toxicity Fluid retention 1. Rea. Ann Hematol Apr;94 Suppl 2:S

28 Monitoring for CV/metabolic Risks in the General Population ABCDE approach to the assessment and management of CV risk 1 In symptomatic patients or those with high cardiovascular risk, consider referral to cardiologist 2 A B C D E Assessment of risk Antiplatelet therapy Blood pressure Cholesterol Cigarette/tobacco cessation Diet and weight management Diabetes prevention and treatment Exercise Adapted from Hsu et al. Clin Cardiol. 2013;36(7): While there are guidelines for assessing and monitoring CV/metabolic risk in the general population, additional research is needed to identify guidelines for assessing and monitoring CV/metabolic risk in the CML patient population CV = cardiovascular 1. Hsu et al. Clin Cardiol. 2013;36(7): Moslehi et al. J Clin Oncol. 2015;10;33(35):

29 Proposed Cardio-Oncology Assessment Algorithm Outline of a general cardio-oncology algorithm 1 Before During After treatment treatment treatment Cardiovascular review (incl. history, examination, CXR, ECG, and echocardiogram) Cardiovascu lar risk? Hematology/Oncology patient Cardiovascu lar complication Cardio-oncology s? consultation CXR = chest x-ray; ECG = electrocardiogram. 1. Herrmann et al. Mayo Clin Proc. 2014;89(9): Moslehi et al. J Clin Oncol. 2015;10;33(35): Cardiovasc ular complicatio ns? Adapted from Herrmann et al. Mayo Clin Proc. 2014;89(9): In symptomatic patients or those with high cardiovascular risk, consider referral to cardiologist 2 29

30 Cardio-Oncology: can we make a difference? In the words of Meredith Durham, who opened our conference with an absolutely fantastic, uplifting and motivating patient presentation: How can we make a difference?!

31 Topics include: How to deliver a Cardio- Oncology service Training in Cardio- Oncology ehealth and Cardio- Oncology How do I measure the quality of my service? Role of primary care in cancer survivors Immunotherapy and emerging cardiotoxicity Personalised medicine & gene>cs EP session who should have abla>on, ICDs, CRT? An>coagula>on and an>thrombo>c (AF, ACS) Radia>on- induced cardiotoxicity Managing cardiac issues during BMSC transplants Cardiac tumours, carcinoid valvular disease, amyloid Hormone therapy and CV risk