Low cardiotoxicity risk with anti-HER2 agents shows treatment can continue

By Mardi Chapman

19 Aug 2020

Cardiotoxicity related to treatment with anti-HER2 therapies is reassuringly low and resolution rates are high, allowing most patients to continue their breast cancer treatment, Australian research shows.

A study of 287 patients with HER2 positive advanced breast cancer from the Australian TABITHA registry, found 6% of patients experienced mainly asymptomatic cardiotoxicity associated with anti-HER2 monotherapy or dual therapy.

Patients had a median of one known risk factor for cardiotoxicity including age >70 years (22%), previous anthracycline use (15%) and pre-existing cardiovascular risk factors (14%).

However the study found that having two or more cardiovascular risk factors significantly increased the risk of anti-HER2 therapy-related cardiotoxicity (OR 3.9; p=0.01).

The only single risk factor associated with risk of cardiotoxicity was a pre-existing diagnosis of cardiovascular disease (OR = 7.1; 95% CI, 1.3–39.5; P = 0.03).

Cardiotoxicity occurred after a median of 9.3 months of anti-HER2 therapy leading to treatment being withheld (76%) and cardiologist-directed management (65%) in most affected patients.

Reassuringly, cardiotoxicity resolved on imaging in 64% of affected patients and 71% were able to continue on first- or second-line anti-HER2 therapy with no recurrent episodes.

Two patients (<1%) who did not experience cardiotoxicity upon exposure to anti-HER2 therapy in the first-line setting, experienced cardiotoxicity with second-line anti-HER2 therapy.

The study, published in the Asia Pacific Journal of Clinical Oncology, concluded that the real world data “provides reassurance for physicians that anti-HER2 therapy can be safely administered for most patients, even in patients with pre-existing risk factors for toxicity.”

The authors said other research had shown dual blockade with trastuzumab and pertuzumab could improve median overall survival from 3.5 to 4.7 years.

“For patients with ABC, the risk of omitting life-prolonging anti-HER2 therapy therapies may therefore be greater than the morbidity associated with cardiotoxicity, unlike patients receiving anti-HER2 therapy in the adjuvant setting.”

The study found 54% of patients were screened for cardiotoxicity by multigated acquisition heart pool scans (MUGA) and 32% by transthoracic echocardiogram (TTE).

Lead author Dr Ciara Conduit, an advanced trainee in medical oncology at Peter MacCallum Cancer Centre, told the limbic the study did not look to determine the reasons for the relatively low rate of screening.

“In patients undergoing curative treatment, it makes sense to regularly evaluate for cardiotoxicity because the morbidity associated with long-term cardiac damage in patients with otherwise excellent survival can be devastating,” she said.

“But maybe we can be more relaxed in patients with advanced breast cancer because the ongoing benefit of anti-HER2 therapies might outweigh that potential risk [of cardiotoxicity], particularly when we can continue treatment after resolution.”

“To counter that, given the poor prognosis associated with heart failure, maybe we should be looking early and treating aggressively from the outset even in women with advanced breast cancer.”

She said more data was required to better define appropriate screening protocols.

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