Is there a "Cardio-friendly" ADT? Professor Bertrand - PowerPoint PPT Presentation

Is there a "Cardio-friendly" ADT? Professor Bertrand Tombal, MD, PhD Cliniques universitaires Saint-Luc Université catholique de Louvain Brussels, Belgium Urologie

Is there a "Cardio-friendly" ADT?  Short-term increased risk of CVD (in men with pre-existing disease)  Most probably a class effect  Long-term metabolic changes in everybody Urologie

Risk factors of CVD Pre-existing cardiovascular morbidity Urologie Nanda et al. JAMA 2009; 302:866-73

Cardiovascular Morbidity Associated with Gonadotropin Releasing Hormone Agonists and an Antagonist. Albertsen PC et al. 2014 Mar;65(3):565-73  Lower incidence of CV events with degarelix vs LHRH agonists in patients with CV history Degarelix, LHRH agonist, n (%) n (%) n=463 n=245 Any CV event 21 (4.5) 23 (9.4) 9 (1.9) 13 (5.3) Death Urologie 4 CV, cardiovascular LHRH, luteinizing hormone-releasing hormone

Cardiovascular Morbidity Associated with Gonadotropin Releasing Hormone Agonists and an Antagonist. Albertsen PC et al. 2014 Mar;65(3):565-73  Lower risk of CV event or death with degarelix in men with baseline CVD HR=0.44 (95% CI 0.26 – 0.74) p=0.002 Urologie HR adjusted by Cox regression for common CV risk factors including age, statin use, hypertension and serum cholesterol CV, cardiovascular; CVD, CV disease; HR, hazard ratio 5 LHRH, luteinizing hormone-releasing hormone Albertsen PC, et al. Eur Urol 2014;65:565 – 73 NNT, number needed to treat

Less CV events with GnRH antagonists compared to the agonists during a median follow up period of 6,3 months 6 patients in the GnRH agonist arm developed a new CV event, none of the patients in the FIRMAGON arm experienced any new CV event. Urologie Margel D et al. J Urol 2017;197(4S):e768 - Abstract MP 57-13

Is there a "Cardio-friendly" ADT?  Short-term increased risk of CVD (in men with pre-existing disease)  Most probably a class effect  Long-term metabolic changes in everybody  Largely a physician effect Urologie

Overall survival….. Urologie

Randomized controlled trial of resistance or aerobic exercise in men receiving radiation therapy for prostate cancer. Segal RJ et al. J Clin Oncol. 2009 27(3):344-51  Median adherence to prescribed exercise was 85.5%.  Resistance (p.010) and aerobic exercise (p.004) mitigated.  Resistance training improved QOL (p.015), aerobic fitness (p.041), upper- (p.001) and lower-body (p.001) strength, and triglycerides (p.036), while preventing an increase in body fat (p.049). Urologie

Randomized controlled trial of resistance or aerobic exercise in men receiving radiation therapy for prostate cancer. Segal RJ et al. J Clin Oncol. 2009 27(3):344-51 Resistance Resistance Aerobic Aerobic Controle Controle 0 2 4 6 -0.5 0 0.5 1 1.5 2 Modification of fatigue Variation of fat mass (Fact P) (%) Urologie

A prospective, randomized pilot study evaluating the effects of metformin and lifestyle intervention on patients with prostate cancer receiving androgen deprivation therapy JP. Nobes et al. BJU Int. 2012;109(10):1495-502 40 men with PCa due to receive ADT randomized standard care vs. 6 months of  metformin, a low glycemic index diet and an exercise programme. Systolic BP (mmHG) Diastolic BP (mmHg) Intervention Control LDL (mM/L) Body fat (%) Abdominal perimeter (cm) Urologie -8 -6 -4 -2 0 2 4 6 8

Is there a "Cardio-friendly" ADT?  Short-term increased risk of CVD (in men with pre-existing disease)  Most probably a class effect  Long-term metabolic changes in everybody  Largely a physician effect  Can we use a drug that doesn’t induce metabolic complications Urologie

Cardiovascular toxicity of antiandrogens Association between androgen deprivation therapy and diabetes, coronary heart disease, myocardial infarction, sudden death, and stroke. 1.6 1.4 1.2 No ADT 1 GnRHa HR 0.8 Orchiectomy 0.6 MAB 0.4 Antiandrogens 0.2 0 Diabetes CHD Urologie Keating N. et al. J Natl Cancer Inst 2010;102: 39 – 46

Cardiovascular toxicity of antiandrogens Association between androgen deprivation therapy and diabetes, coronary heart disease, myocardial infarction, sudden death, and stroke. 2.5 2 No ADT 1.5 GnRHa HR Orchiectomy 1 MAB Antiandrogens 0.5 0 Myocardial Infarction Cardiac death Urologie Keating N. et al. J Natl Cancer Inst 2010;102: 39 – 46

Lancet Oncol. 2014 May;15(6):592-600. Urologie Eur Urol. 2015 Nov;68(5):787-94.

Metabolic changes under enzalutamide monotherapy Urologie

Is there a "Cardio-friendly" ADT?  Short-term increased risk of CVD (in men with pre-existing disease)  Most probably a class effect  Long-term metabolic changes in everybody  Largely a physician effect  Can we use a drug that doesn’t induce metabolic complications Urologie