Avirup Guha: Early Immune Responses to Androgen Deprivation Therapy and Coronary Plaque Progression
Avirup Guha, Director of Cardio-Oncology at Georgia Cancer Center, Assistant Professor Of Medicine at Medical College of Georgia at Augusta University, Adjunct Assistant Professor of Medicine at The Ohio State University Wexner Medical Center, shared a post on LinkedIn:
“At AHA Scientific Sessions, ZEUS raised a question for my cardio-oncology research. Can we identify an early immune response to androgen deprivation therapy (ADT) that predicts later coronary plaque progression?
ZEUS enrolled 6,376 people with established atherosclerotic cardiovascular disease, chronic kidney disease, and elevated hsCRP.
Ziltivekimab lowered hsCRP. Major cardiovascular events occurred in 17.6% versus 17.7% on placebo (HR 0.99), and serious infections were more frequent with ziltivekimab.
In REVELUTION, coronary plaque progressed more over 12 months with leuprolide than with relugolix. I’d measure IL-6 signaling and monocyte responses before ADT and at three months, then assess plaque on coronary CT at 12 months.
If a reproducible signal responds to pathway inhibition in the lab, I’d consider a randomized prevention trial that tracks plaque progression, serious infections, and cancer control.
Direct antitumor activity is a separate question. In SWOG S0354, the IL-6 antibody siltuximab produced two PSA responses among 53 men with previously treated castration-resistant prostate cancer and zero objective responses among the 31 with measurable disease.
Which ADT population would you enroll first in a cardiovascular prevention trial?”
Title 1: Interleukin-6 Inhibition with Ziltivekimab for Atherosclerotic Disease
Authors: Paul M. Ridker, A. Michael Lincoff, Nikolaus Marx, Ann Marie Navar, Naveed Sattar, Katherine R. Tuttle, Matthew Budoff, Morten Böttcher, Matthew A. Cavender, Robin P. Choudhury, Jan H. Cornel, Grzegorz Gajos, Issei Komuro, K.M.K. Reddy Parvathareddy, Roberto Pontremoli, José Francisco Kerr Saraiva, Iana I. Simova, Lance A. Sloan, Alejandro López-Suárez, Yi-Da Tang, Lale Tokgözoğlu, Nqoba Tsabedze, Konstantinos Tsioufis, Subodh Verma, Mathias Vrolix, Andreas Andersen, Florian M.M. Baeres, Kathrine Ekström, Mads D.M. Engelmann, Sofia Gerward, G. Kees Hovingh, Anders Hvelplund, Vlado Perkovic
Read the Full Article on NEJM
Title 2: Coronary Plaque Progression After Androgen Deprivation Therapy in Men With Prostate CancerA Randomized Clinical Trial
Authors: Sagar A. Patel, Adithya K. Yadalam, Marly van Assen, Stephanie M. Cantu, Carlotta Onnis, Bill Zheng, Andee Koo, Subir Goyal, Yuan Liu, Chang Liu, Nikhil T. Sebastian, Vishal R. Dhere, Bruce W. Hershatter, Pretesh R. Patel, Kiranj Chaudagar, Arthur E. Stillman, Carlo N. De Cecco, Martin G. Sanda, Ashesh B. Jani, Anant Mandawat
Read the Full Article on JAMA Cardiology
Title 3: Clinical and correlative results of SWOG S0354: a phase II trial of CNTO328 (siltuximab), a monoclonal antibody against interleukin-6, in chemotherapy-pretreated patients with castration-resistant prostate cancer
Authors: Tanya B Dorff, Bryan Goldman, Jacek K Pinski, Philip C Mack, Primo N Lara Jr, Peter J Van Veldhuizen Jr, David I Quinn, Nicholas J Vogelzang, Ian M Thompson Jr, Maha H A Hussain
Read the Full Article on Clinical Cancer Research
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