Towards an "N-of-1" Approach to Cardio-Oncology Drug Interactions

Introduction

Heart disease and cancer continue to top the list as the most common causes of death in the United States over the past five years.¹ Compounding the issue, adverse effects involving the cardiovascular system represent one of the most significant challenges when treating patients with hematologic or solid tumor malignancies. Cardiovascular toxicities related to cancer therapies are as diverse as each individual patient, have a significant impact on cancer patients' morbidity and mortality, and occur across all treatment modalities.^{2, 3}

As precision medicine in cancer treatment evolves, and therapies become ever more targeted, the implications for potential medication interactions related to cardio-oncology will increase. The understanding that a genomic roadmap drives cancer cell growth, rather than just the tissue of origin and histology subtype, can improve outcomes across a wide variety of cancers. Early studies of this approach suggest feasibility, safety, and efficacy.⁴

High levels of tumor heterogeneity and genomic complexity differing from patient to patient suggest individualized “N-of-one” therapy combinations are a necessary next step for treatment optimization.⁵ Optimized treatment often involves drug combinations (rather than sequential monotherapy), and dose customization. Anticancer therapies extend the lives of patients with cancer, but for many this benefit is attenuated by the development of adverse cardiovascular effects directly related to drug therapy. As treatment modalities combine and are administered together based on individual genomic variation of tumors, the potential for Cardio-Oncology drug interactions will increase and close monitoring for adverse effects will be crucial.

Key Points

The new AHA scientific statement on Cardio-Oncology Drug Interactions is a welcome comprehensive resource outlining key principles of potential drug class and drug specific interactions affecting patients at risk for cardiovascular complications from anticancer treatment.⁶ This consensus article provides guidance on prevention, screening, monitoring and treatment of cardiovascular toxicities specifically related to medications used in the treatment of cancer.

To provide context, the authors highlight two key pillars of drug interactions – pharmacokinetic (PK) drug interactions and pharmacodynamic (PD) drug interactions. Pharmacokinetics is the study of drug absorption, distribution, metabolism, and excretion – in essence, “what the body does to the drug.” Pharmacodynamics is the study of biochemical and physiological effects of drugs – or, “what the drug does to the body.” The interplay of the two help determine the clinical effects of drug therapy.⁷

Recommended preventative as well as monitoring strategies for cancer drugs associated with risk of cardiovascular toxicities are proposed, as well as direction on the management of adverse effects should they occur. Acknowledging patient and drug specific characteristics can affect the incidence and severity of drug-drug interactions, the authors provide an outline of both PD (Table 1) and PK (Table 2) considerations. Table 3 in particular highlights recommendations for the management of select clinically significant drug-drug interactions with cardiovascular and anticancer agents.

Future Directions

Establishment of a Cardio-Oncology clinic is an integral part of providing specialized care to cancer patients currently receiving treatment, as well as cancer survivors who are at risk of delayed cardiovascular complications.⁸ Training of multidisciplinary cardio-oncology clinical teams should expand to include recognition of potential cardio-oncology drug interactions. Leveraging an interdisciplinary strategy by including cardiology and oncology trained pharmacists acting as medication experts as part of the Cardio-Oncology care team is critical to mitigating medication misadventures, as well as prolonging the highest quality of life post treatment.

A diverse approach to the cardiovascular care of cancer patients is also essential to achieve optimal long-term outcomes and quality of life. Employing available technology to provide virtual monitoring and “web-side” care and follow up is not only feasible, but should be considered when patients are receiving cancer treatment at high risk of causing cardiac complications and require intensive monitoring.^{9, 10}

Molecular interrogation of cancer cells has revealed the need for a patient-centric model of cancer treatment, with customized combinations of drugs based on the tumor biology of each individual. As we move forward into uncharted territories combining cancer treatment modalities in ways not previously seen based on individual genomic variation of tumors, close monitoring for adverse effects will be essential.