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Trastuzumab increased heart failure risk in older patients with breast cancer
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Older patients with breast cancer treated with trastuzumab were at increased risk for congestive heart failure, according to study results.
This risk — higher than that reported in previous clinical trials — was elevated in patients aged older than 80 years or those with cardiac comorbidities.
Researchers used the SEER-Medicare and Texas Cancer Registry-Medicare databases to identify 9,535 patients who underwent chemotherapy for stage I to III breast cancer diagnosed between 2005 and 2009. The patients were aged 66 years or older (median age, 71).
Of the study population, 2,203 patients (23.1%) received trastuzumab (Herceptin, Genentech).
The incidence of congestive heart failure was significantly higher in patients who received trastuzumab than those who did not (29.4% vs. 18.9%; P˂.001). Researchers calculated an HR of 1.95 (95% CI, 1.75-2.17) for congestive heart failure after treatment with trastuzumab.
The risk for congestive heart failure associated with trastuzumab increased in patients aged older than 80 years (HR=1.53; 95% CI, 1.16-2.10), those with coronary artery disease (HR=1.82; 95% CI, 1.34-2.48) or hypertension (HR=1.24; 95% CI, 1.02-1.50), and those who received weekly administration of trastuzumab (HR=1.33; 95% CI, 1.05-1.68).
“Congestive heart failure rates among older patients treated with trastuzumab are higher than the rates that have been reported among clinical trial participants,” the researchers wrote. “It is possible that among high-risk patients, early cardiology referral, the use of prophylactic cardioprotective agents and close monitoring may be beneficial.”
Disclosure: The researchers report consultant or advisory roles with, as well as research funding from, Allergan, Antigen Express, Genentech and Novartis.Perspective
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Trastuzumab-based chemotherapy has become the standard of care for HER-2–positive breast cancer. The natural history of HER-2–positive breast cancer has clearly been changed by the addition of trastuzumab, and the outcomes of early stage HER-2–positive breast cancer are excellent. Given this, it does make sense to examine the toxicities of trastuzumab-based therapy.
In this article, a cancer registry-based approach was used to identify the incidence and risk factors for congestive heart failure associated with trastuzumab use. The rate of congestive heart failure was higher with trastuzumab use than with nonuse (29.4% vs. 18.9%) in this older population. Age older than 80 years, prior coronary artery disease, hypertension and weekly trastuzumab use were associated with congestive heart failure in a multivariate analysis. Interestingly, and unlike a prior publication, anthracycline use with trastuzumab was not associated with congestive heart failure.
These data, in combination with prior studies, can give all of us some ideas of who will be more likely to develop cardiac toxicity with trastuzumab administration so we can temper our use of this antibody appropriately.
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