Cardiovascular Risk Assessment in Oncological Clinical Trials: Is there a Role for Centralized Events Adjudication?

Oncological drugs, including certain monoclonal antibodies, cytotoxic agents, and tyrosine kinase inhibitors are increasingly appreciated as carrying dose-related cardiotoxic effects.The expanding use of these agents in older patients and in those with greater co-morbid disease burden has accentuated the harms in real-world use compared with randomized controlled trials. 1 Until recently, the formal evaluation of treatment-related cardiovascular risk had been reserved for cardiac, weight loss, and diabetic drugs.In 1997, the well-publicized withdrawal of the anorectic agents fenfluramine and phentermine due to increased post-marketing reports of valvular heart disease 2 and pulmonary hypertension raised awareness of unexpected cardiovascular effects.Since then, a number of therapeutics have been either withdrawn from the market or placed under restricted use due to concerns regarding cardiotoxicity.Most recently, the dipeptidyl peptidase (DPP)-4 inhibitors have come under scrutiny for an increased risk for hospitalization for heart failure (HF) among diabetic patients. 3These cases, and the controversy surrounding the diabetic drug, rosiglitazone, have altered the regulatory approval model for certain non-cardiovascular agents. 4Currently, new drug applications submitted to the Food and Drug Administration (FDA) for novel antidiabetic therapies are required to exclude excess cardiovascular risk.Unfortunately, a uniform, standardized approach to cardiovascular risk assessment, reporting, monitoring, and treatment modification is presently lacking for cancer drugs.Herein, we critically evaluate contemporary clinical trial practice and discuss the benefits of shifting to a paradigm of formalized cardiovascular risk assessment in oncological clinical trials. The status quo: endpoint assessment in oncological trialsContemporary clinical trials in oncology have employed varying strategies for detecting cardiotoxicity.Common terminology