Prostate Cancer Therapy Cardiotoxicity Map (PROXMAP) for Advanced Disease States: A Systematic Review and Network Meta-analysis with Bayesian Modeling of Treatment Histories.
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Aziz Moez Karim, Molony Donald, Monlezun Dominique, Holder Travis, Brunckhorst Oliver, Higgason Noel, Roland Jerry, Magill Resa, Fatakdawala Mariya, Iacobucci Alexander, Mody-Bailey Neal, Owen Chris, Zarker Andrew, Thames Emma, Swaby Justin, Xiao Daniel, Choi Lily, Desai Shubh, Galan Jacob, Deng Brett, Hartshorne Taylor, Nichols Alexis, Zhang Allan, Imber Jared, Song Jeffrey, Jones William, Rivas Alexis, Sanchez Darren, Guhan Maya, Gandaglia Giorgio, Ranganath Shreyas, Jacob Jerril, Howell Skyler, Plana Juan, van den Bergh Roderick, Roberts Matthew, Sommer Silke Gillessen, Oldenburg Jan, Ploussard Guillaume, Tilki Derya, Schoots Ivo, Briers Erik, Stranne Johan, Rouviere Olivier, van Oort Inge, Oprea-Lager Daniela, De Santis Maria, Cornford Philip, European Association of Urology Prostate Cancer Guidelines Panel, Koutroumpakis Efstratios, Ziaolhagh Ali, Ali Abdelrahman, Wamique Yusuf Syed, Iliescu Cezar, Canfield Steven
Аннотация
METHODS: We searched Ovid Medline, Elsevier Embase, and the Cochrane Library for randomized clinical trials (RCTs) from database inception to January 14, 2024. Network meta-analyses of first-line mHSPC, M0CRPC, and mCRPC therapies were constructed for the five cardiotoxicity metrics defined by the International Cardio-Oncology Society: heart failure, myocarditis, vascular toxicity, hypertension, and arrhythmias. Additional Bayesian network meta-analyses also accounted for prior treatment history.
KEY FINDINGS AND LIMITATIONS: Thirteen RCTs (16 292 patients) were included. For mHSPC, androgen deprivation therapy (ADT) plus docetaxel (DTX) plus abiraterone acetate (AA) with prednisone (P) demonstrated a significant increase in hypertension and arrhythmias versus ADT + DTX (risk ratio [RR] 2.85, 95% confidence interval [CI] 1.67-4.89, and RR 2.01, 95% CI 1.17-3.44, respectively); however, no corresponding differences were observed between ADT + DTX plus darolutamide (DAR) and ADT + DTX (RR 1.55, 95% CI 0.73-3.30, and RR 0.94, 95% CI 0.63-1.40, respectively). For mCRPC assuming a history of mHSPC treatment, ADT + AA + P plus olaparib (OLA) demonstrated a statistically significant decrease in hypertension versus ADT + AA + P (RR 0.20, 95% CI 0.16-0.26). M0CRPC results were unremarkable.
CONCLUSIONS AND CLINICAL IMPLICATIONS: For mHSPC, ADT + DTX + DAR demonstrates less cardiotoxicity than ADT + DTX + AA + P due to a lower risk of hypertension and arrhythmias from decreased mineralocorticoid excess. In addition, OLA counterintuitively offers decreased hypertension when superimposed on ADT + AA + P for mCRPC treatment after prior androgen deprivation from mHSPC therapy.