Cardiotoxicity with Targeted Therapies Is Rare, but Requires Attention

TON - September 2017, Vol 10, No 5 - Conference Correspondent
Phoebe Starr

Washington, DC—Unanticipated cardiotoxicity occurs in an estimated 3.5% of patients with hematologic malignancies secondary to the use of targeted therapies, according to the results of a retrospective study presented at the 2017 Annual Meeting of the American Association for Cancer Research. In a multivariate analysis, a history of deep vein thrombosis or pulmonary embolism and a high Kar­nofsky score of ≥80% emerged as significant risk factors for cardiotoxicity (P = .011 and P = .005, respectively).

Although this is a small percentage of patients, the findings imply that oncologists and/or hematologists should collaborate with cardiologists to manage this toxicity when it occurs. Conventional risk factors for cardiac events do not seem to apply in this group of patients, with the exception of deep vein thrombosis or pulmonary embolism.

“It is surprising that patients with a high Karnofsky score were at greater risk for unanticipated cardiotoxicity, but patients with a low score probably received less chemotherapy. The underlying mechanisms that lead to cardiomyopathy could be the same ones that cause DVT/PE [deep vein thrombosis/pulmonary embolism],” said lead investigator Chintan Shah, MD, Assistant Professor, Division of Hospital Medicine, University of Florida, Gainesville.

Of 820 patients who met the International Classification of Diseases codes for hematologic malignancies treated with targeted therapy and a cardiac diagnosis (ie, left ventricular ejection fraction <50%, arrhythmias, or ischemic cardiac event), 29 had cardiac diagnoses after initiation of a targeted therapy.

Among these 29 patients (the study group), targeted therapies, such as rituximab (n = 10), multitargeted tyrosine kinase inhibitors (n = 3), immunomodulatory agents (n = 4), and proteasome inhibitors (n = 12) were used. Seventy matched controls were selected from the 820 patients based on type of targeted therapy. Both groups had comparable baseline demographics, including age, sex, race, body mass index, and hematologic malignancies. The control group had more men than the study group (62% vs 43%, respectively). Median time from exposure to cardiac event was 120 days (range, 1-1176 days).

At a median follow-up of 27 months (range, 1-120 months), 3.5% of patients developed cardiotoxicity related to targeted therapy, and 17 patients in the study group died—but only 2 (6.8%) of these deaths were caused by cardiac issues. Repeat echocardiograms showed worsening of left ventricular ejection fraction in 4 patients, whereas stable or improved results were observed in 23 patients; 21 patients were able to receive further chemotherapy. Median survival was 36 months for the study group (with cardiomyopathy), and 94 months for controls (with no cardiomyopathy), for an adjusted hazard ratio of 2.19 for mortality (95% confidence interval, 1.16-4.16; P = .016).

“Most patients do well, with stable or improved cardiac function, but overall survival was worse in this group. We strongly recommend collaborative efforts between the hematologist and/or oncologist and the cardiologist for optimal treatment of these toxicities,” Dr Shah told attendees.

Rituximab plus or minus other therapy was used in 10 of the 29 patients who developed cardiotoxicity. At least 4 patients had no exposure to anthracyclines, and most had normal ejection fractions prior to rituximab, but ejection fraction was lower after rituximab.

“The cardiotoxic potential of rituximab is not clear. Studies are conflicting,” Dr Shah concluded.

Related Items
Emerging Safety Data with Checkpoint Inhibitors
Phoebe Starr
TON - November 2017, Vol 10, No 6 published on November 27, 2017 in Conference Correspondent
Psychological Distress in Patients with Cancer Warrants Attention
Phoebe Starr
TON - November 2017, Vol 10, No 6 published on November 27, 2017 in Conference Correspondent
Patients’ Chemotherapy-Related Side-Effect Concerns Have Evolved, But Hair Loss Remains Significant
Phoebe Starr
TON - November 2017, Vol 10, No 6 published on November 27, 2017 in Conference Correspondent
Increased Cancer Risk in Postmenopausal Women with Central Obesity
Phoebe Starr
TON - November 2017, Vol 10, No 6 published on November 27, 2017 in Conference Correspondent
Patients’ Fears of Radiation Side Effects Largely Unfounded
Phoebe Starr
TON - November 2017, Vol 10, No 6 published on November 27, 2017 in Conference Correspondent
Novel Drug “Home Run” for TRK Mutation–Positive Tumors
Phoebe Starr
TON - November 2017, Vol 10, No 6 published on November 27, 2017 in Emerging Therapies
Netupitant plus Palonosetron Noninferior to Aprepitant plus Granisetron in Patients Receiving Highly Emetogenic Chemotherapy
Li Zhang, MD
TON - November 2017, Vol 10, No 6 published on November 27, 2017 in Conference Correspondent
Alectinib New Standard of Care for ALK-Positive Non–Small-Cell Lung Cancer
Phoebe Starr
TOP - November 2017, Vol 10, No 4 published on November 13, 2017 in Lung Cancer
Pembrolizumab Makes Inroads in Sarcoma Subtypes
Phoebe Starr
TOP - November 2017, Vol 10, No 4 published on November 13, 2017 in Immunotherapy, Online First
Abemaciclib, a New CDK4/CDK6 Inhibitor, Added to Fulvestrant Extends PFS in Advanced HR-Positive, HER2-Negative Breast Cancer
Phoebe Starr
TOP - November 2017, Vol 10, No 4 published on November 13, 2017 in Breast Cancer
Last modified: September 18, 2017