It has been almost 20 years since the approval of trastuzumab for the treatment of early-stage, HER2-positive breast cancer. I remember returning from the 2005 ASCO Annual Meeting excited to offer patients a treatment that led to significant improvement in clinical outcomes. However, within a short period, this enthusiasm was partly dampened by concern of potential cardiotoxicity—clinicians were seeing drops in left ventricular (LV) ejection fraction, leading to the postponement or cancellation of life-prolonging therapy.
Over the past few decades, clinicians have gained a better understanding of the impact of HER2-targeted therapies on cardiac function, with most patients now completing treatment—even those with compromised LV function with appropriate medical management. However, the pace of drug discovery has accelerated, as has the need for oncologists to understand the potential benefits and toxicities of these new agents.
Susan Faye Dent, MD, FRCPC, FIC-OS
Today, there are more than 3,500 compounds with potential anticancer effects in development,1 and, in 2022 alone, the U.S. Food and Drug Administration (FDA) approved 12 novel anticancer drugs and biologics.2 Many targeted therapies are associated with cardiovascular toxicity, including heart failure (eg, HER2-targeted agents), arrhythmias (atrial fibrillation with Bruton’s tyrosine kinase inhibitors and QT prolongation with histone deacetylase [HDAC] inhibitors), vascular toxicity (eg, capecitabine), hypertension (eg, tyrosine kinase inhibitors), and myocarditis (eg, immune checkpoint inhibitors).3 Furthermore, our population is aging, and patients with cancer may have cardiac risk factors (eg, hypertension) or preexisting cardiovascular disease, elevating the risk of cardiovascular toxicity during the acute (active), subacute (first 12 months after completion of cancer treatment), and long-term (beyond 12 months after anticancer therapy) phases of cancer therapy.
The Intersection of Cancer and Cardiovascular Health
Our focus as oncologists has been on “curing” patients with cancer—and we are doing a great job! The number of cancer survivors living in the United States is projected to reach 22.2 million by 2030.4 However, what is the long-term impact of modern cancer treatment? Improved cancer survival means that cardiovascular disease now assumes a greater relative importance than it previously did, both during and after cancer therapy. Postmenopausal women, several years out from their cancer diagnosis, are more likely to die of cardiovascular disease than recurrent cancer.5
Cardio-oncology has emerged as a subspecialty of medicine dedicated to ensuring patients receive the best cancer therapy while optimizing cardiovascular health. This requires a multidisciplinary approach, including input from oncologists/hematologists, cardiologists, pharmacists, nurses, and allied health-care professionals. Collectively, we must turn to a more “patient-centered” approach in the management of patients with cancer, taking into consideration underlying comorbidities, life-style behaviors, genetics, and social determinants of health when prescribing cancer therapy—all of which will influence the long-term cardiovascular morbidity and mortality of patients.6
Several international organizations have endorsed a cardio-oncology partnership, including ASCO, the European Society for Medical Oncology (ESMO), the European Society of Cardiology (ESC), the American College of Cardiology (ACC), and the American Heart Association (AHA). The ACC, AHA, and ESC have dedicated working groups or councils focusing on cardio-oncology. The International Cardio-Oncology Society (ICOS: www.ic-os.org) is a grassroots, “not-for-profit” organization that emerged in 2009 because of the efforts of a small group of dedicated clinicians. This organization, with a mandate of improving clinical care, educating health-care providers and patients, and promoting research, has more than 1,000 members (approximately 10% are oncologists) and 30 country chapters, and hosts an annual meeting (Global Cardio-Oncology Summit [GCOS]) with more than 500 attendees.
Are Collaborations Impacting Patient Care?
Several guidelines and/or position statements have been published over the past decade to guide clinicians in best practices for the care of patients at risk of cancer therapy–related toxicity. In 2022, the ESC cardio-oncology guideline provided 272 new recommendations on risk prediction, management, and surveillance strategies for patients with cancer treated with potential cardiotoxic therapy.7 Many of the recommendations in this guideline are based on low-quality evidence or expert opinion, thus stressing the need for further research.
Are these collaborations having a positive impact on patient care? Over the past 20 years, we have seen the establishment of dedicated cardio-oncology clinics and programs emerge across North America, Europe, South America, Asia, South Africa, and Australia; however, many of these clinics are in academic centers or large cities, where there is more infrastructure support, and most clinics are led by cardiologists. Is this the best care delivery model for cardio-oncology?
Improved cancer survival means that cardiovascular disease now assumes a greater relative importance than it previously did, both during and after cancer therapy.— Susan Faye Dent, MD, FRCPC, FIC-OS
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A Shared Leadership Model
Although academic centers may be able to provide the infrastructure needed for a cardio-oncology program, most of the cancer care in the United States is delivered in nonacademic centers. Can we harness the knowledge we gained from the COVID-19 pandemic to explore different models of care delivery (eg, telemedicine) to ensure all patients in need have access to cardio-oncology services?
Most cardio-oncology clinics and programs are led by cardiologists, but is this the best model? If this is a true partnership and collaboration, a shared leadership model would make sense. Yet there are few oncologists/hematologists in such leadership positions. Why?
The cardiology community has fully embraced gaining a better understanding of the impact of modern cancer therapies on cardiovascular health (eg, immune checkpoint inhibitor–induced myocarditis) in patients with cancer. The AHA, ACC, and ESC annual meetings have cardio-oncology tracks focusing on research in the prevention and management of cancer treatment–related cardiac dysfunction, and several fellowship programs have emerged in the United States and Europe.
“Position papers and guidelines are of little value if they are not endorsed or implemented by all members of the multidisciplinary team.”— Susan Faye Dent, MD, FRCPC, FIC-OS
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In contrast, cardio-oncology among the oncology community has a very limited reach. Only a handful of oncologists in North America or globally have an academic interest in cardio-oncology, and there is little presence at international meetings such as ASCO or ESMO. A true partnership requires all parties to work together to improve the care of patients. This can only be accomplished with the input and leadership of oncologists, cardiologists, and allied health-care professionals. Position papers and guidelines are of little value if they are not endorsed or implemented by all members of the multidisciplinary team.
A Call to Action
To my oncology colleagues, it is time to engage and work with your cardiology colleagues to identify and prevent the potential life-altering cardiovascular consequences of cancer therapy. We need to educate our colleagues, including primary care providers and allied health-care providers, as well as patients on the importance of cardiovascular health from the time of cancer diagnosis throughout survivorship. Cardio-oncology education should be integrated into all major oncology meetings, such as ASCO, ESMO, and the American Society of Hematology (ASH).
Oncologists should be asking what they can learn from the most recent ESC cardio-oncology guidelines and how they can incorporate this information into their daily clinical practice to improve patient care. We need to promote research in cardio-oncology to have a better understanding of how to deliver novel cancer drugs to patients safely without long-term cardiovascular toxicity.
The future is looking much brighter for patients diagnosed with cancer in 2024! Let’s work together to not only cure cancer, but ensure patients live a long and healthy life. Cure cancer, save hearts!
DISCLOSURE: Dr. Dent has received honoraria from Novartis, Pfizer, Race Oncology, Bristol Myers Squibb, Myocardial Solutions, Gilead Sciences, and AstraZeneca.
REFERENCES
1. PharmaWeb: Global Oncology Innovation Continues Despite Pandemic. Available at https://www.pharmiweb.com/press-release/2021-06-03/global-oncology-innovation-continues-despite-pandemic-global-rd-pipeline-reached-3-500-new-drugs-i. Accessed January 19, 2024.
2. U.S. Food and Drug Administration: Novel Drug Approvals for 2022. Available at https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/novel-drug-approvals-2022. Accessed January 19, 2024.
3. Herrmann J, Lenihan D, Armenian S, et al: Defining cardiovascular toxicities of cancer therapies: An International Cardio-Oncology Society (IC-OS) consensus statement. Eur Heart J 43:280-299, 2022.
4. National Cancer Institute: Cancer Statistics. Available at https://www.cancer.gov/about-cancer/understanding/statistics#:~:text=The%20number%20of%20cancer%20survivors,on%202015%E2%80%932017%20data). Accessed January 19, 2024.
5. Ramin C, Schaeffer ML, Zheng Z, et al: All-cause and cardiovascular mortality among breast cancer survivors in CLUE II, a long-standing community-based cohort. J Natl Cancer Inst 113:137-145, 2021.
6. Zullig LL, Sung AD, Khouri MG, et al: Cardiometabolic comorbidities in cancer survivors: JACC: CardioOncology state-of-the-art review. JACC CardioOncol 4:149-165, 2022.
7. Lyon AR, López-Fernández T, Couch LS, et al: 2022 ESC guidelines on cardio-oncology developed in collaboration with the European Hematology Association, the European Society for Therapeutic Radiology and Oncology and the International Cardio-Oncology Society. Eur Heart J 43:4229-4361, 2022.
Dr. Dent is Professor of Medicine at Duke University School of Medicine; Associate Director of Breast Cancer Clinical Research; and Co-Director of the Cardio-Oncology Program at Duke Health, Durham, North Carolina.
Disclaimer: This commentary represents the views of the author and may not necessarily reflect the views of ASCO or The ASCO Post.
