Cardiotoxicities & Genomic-Guided Treatments: Issues for Treatment Decision-Making, Monitoring, & Management

Dr. Fred Ashbury, PhD, Chief Scientific Officer, VieCure:

An interview with Dr. Maryam Lustberg, MD, Chief, Breast Medical Oncology, Yale Cancer Center

October 28, 2021

ORION by VieCure

Volume 2, Issue 5

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Fred Ashbury: Cardiotoxic side effects of cancer chemotherapies have been known and treated for some time. With the increase in the use of targeted therapies and immunotherapies, are there particular issues physicians need to consider that are unique to these medications compared to chemotherapy agents?
Maryam Lustberg: Yes, with the emerging genomicguided therapies the potential for both acute and late term toxicities need to be considered.  Acute cardiac toxicities are naturally recognized first. Most relevant now is the acute myocarditis seen with the newer immunotherapy agents such as check point inhibitors.1 Early recognition by the clinical team is paramount given the potential for deadly complications.
Further, many targeted therapies can be associated with early onset cardiovascular complications such as QTC prolongation; for example, we see hypertension with the tyrosine kinase inhibitors.2 Some targeted therapies such as mTOR inhibitors predispose patients to hyperglycemia, thrombocytopenia, skin toxicities, stomatitis, anemia and fatigue, to name some.
Late-onset toxicities are more challenging to initially recognize and often need both data maturity and power in terms of larger population samples to identify patterns such as increases in cardiovascular events including cardiovascular disease, cardiomyopathies, arrythmias, and hypertension. An easily recognized example of this pattern is with the older class of drugs such as anthracyclines. With these new drugs, time will tell which toxicities will occur longer term or not.
FA: Are there any tests physicians should order and when should these be ordered to monitor patients during treatment with genomic-guided therapies?
ML: The era of precision medicine is comparatively in its infancy, although it is rapidly growing; currently, a fraction of patients who undergo genomic sequencing of tumor tissue or blood, have targeted genomic guided therapies identified but the great news is that research into new targets continues and more patients will be eligible for these novel therapies. As with any cancer therapeutic drug, with each of these options, it is important to have a thorough discussion of potential toxicities and side effects including the need for cardiovascular monitoring based on the specific agent. Monitoring may include EKGs, lipid profile checks, cardiac function monitoring or close co-management with a cardio oncologist. It is important also that clinicians continue to capture data on patients’ experiences, including the use of patient-reported outcomes, which will allow us to identify problems earlier and over time so that appropriate interventions can be applied.
FA: How long after treatment should patients be monitored for cardiotoxicities who have received targeted agents or immunotherapies? Are there any guidelines?
ML: The guidelines are evolving in this space and how patients are monitored very much currently depends on whether they will be receiving ongoing therapy, their cardiovascular risk factors and whether they have experienced any prior cardiotoxic events. Evidence is pointing to the need for monitoring in selected populations for at least a few years post treatment with these novel agents.
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FA: What management strategies should oncologists use when patients experience a cardiotoxic event as a result of targeted therapy or immunotherapy? What do they need to consider?
ML: A multidisciplinary approach that includes cardiology as well primary care is very important. Close communication with both the patient and each of these specialities to discuss goals of care, and coordinate a unified plan of care is essential. A patient with multiple cardiovascular risk factors undergoing cardiotoxic cancer therapies will particularly benefit from this approach. However, this is sometimes easier said than done due to the complexity of health care system access and availability of providers to address these issues as a team. Implementation of cardio oncology care is a subject of ongoing research efforts.
FA: What data are needed on cardiotoxicities and genomic-guided therapies that community oncology practices can help provide?
ML: Precision medicine is not only for treatment, it also means precision medicine for supportive care. At point-of-care we need decision-support tools that can alert physicians to potential risks associated with these novel agents. Cancer care has become so complex over the last few years that frankly it is impossible for any one person to stay on top of everything that is happening without access to these tools. Artificial intelligence platforms that would help process these complex data would be a great asset in the oncology setting. In addition, real world registries and real-world data on cardiotoxicities experienced by patients not on clinical trials are very important. Unusual events should be reported and shared with the entire medical community and through different regulatory agencies (e.g., MedWatch). We also need to design proactive intervention trials to lower cardiovascular morbidity among cancer survivors as well as conduct mechanistic biologically sound intervention studies to improve cardiotoxicity once it occurs.



References:
  1. Daniela Lobenwein , Florian Kocher , Stephan Dobner , Can Gollmann-Tepeköylü, Johannes Holfeld . Cardiotoxic mechanisms of cancer immunotherapy - A systematic review. Int J Cardiol2021 Jan 15;323:179-187 doi: 10.1016/j.ijcard.2020.08.033. Epub 2020 Aug 12.

  2. Javed Moslehi. Cardiovascular Toxic Effects of Targeted Cancer Therapies. N Engl J Med 2016 Oct 13;375(15):1457-1467.doi: 10.1056/NEJMra1100265.
     

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Fredrick D. Ashbury, PhD
Chief Scientific Officer, VieCure
Professor (Adj), Department of Oncology University of Calgary
Professor (Adj), DLSPH, University of Toronto

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Maryam Lustberg, MD
Chief, Breast Medical Oncology, Yale Cancer Center