Tagrisso Associated With Cardiac Side Effects in Non-Small Cell Lung Cancer

Tagrisso in pateints with EGFR-mutant NSCLC is linked to higher cardiac side effects, including arrhythmia and heart failure, which negatively impact overall survival.

Among patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), Tagrisso (osimertinib) was associated with a higher incidence of cancer therapy-related cardiac side effects (CTRCEs) compared with other EGFR tyrosine kinase inhibitors (TKIs), and CTREs were independently associated with reduced overall survival, according to study findings published in JAMA Network Open.

Furthermore, study authors highlight the need for ongoing cardiac monitoring in patients with this disease, regardless of preexisting cardiac risk factors.

Previous studies have suggested that CTRCEs that are associated with Tagrisso predominantly occur in patients with preexisting cardiovascular disease or cardiovascular risk factors, as per the study.

Despite this, “We found a higher cumulative incidence of CTRCEs in the [Tagrisso] group compared with the other EGFR TKI group,” study authors wrote. “Even patients with low cardiovascular risk while receiving [Tagrisso] had a higher hazard of CTRCEs. These findings provide important new

insights.”

After a median follow-up of 23.2 months, the incidence of CTRCEs was significantly higher in patients receiving Tagrisso compared with those treated with other EGFR TKIs: 29 (14.9%) versus nine (4.4%). Tagrisso was linked to a four-fold increased risk of CTRCEs compared to the control group, even after accounting for cardiovascular risk factors. Patients with CTRCEs had four times’ decrease in overall survival compared to those without.

According to study authors, “this [overall survival] remained unassociated with preexisting cardiovascular disease or traditional risk factors, underscoring the necessity for vigilant cardiac monitoring in this patient population.”

Other variables that were independently associated with overall survival included age, stage of disease, brain metastasis (spreading of cancer) and performance status score.

Additionally, the Tagrisso group had a significantly higher likelihood of newly developed arrhythmia and heart failure compared with the group receiving other EGFR-TKIs.

CTRCEs that were reported during the trial period included newly emerging arrhythmias, moderate or worse valvular heart disease, myocardial infarction and heart failure. Side effects were analyzed after adjusting for age, sex, smoking, alcohol consumption, body mass index, cardiovascular comorbidities, thoracic radiotherapy and cardiovascular medications.

A total of 401 patients were enrolled in the study, of which 195 (48.6%) were treated with Tagrisso and 206 (51.4%) were treated with other EGFR TKIs. The mean age was 69.2 years; 63.1% were female, 82.5% were nonsmokers, 42.4% had hypertension and 20% had diabetes or hyperlipidemia. Medications included ACE inhibitors/ARBs (20.2%), statins (19%) and β-blockers (13.7%), with 27.9% undergoing thoracic radiotherapy.

According to the National Cancer Institute’s website, EGFR inhibitors block the epidermal growth factor receptor protein, which can promote cancer cell growth. Blocking EGFR may inhibit this growth. Some EGFR tyrosine kinase inhibitors treat cancer.

The study's primary end goal was CTRCEs, defined as newly emerging arrhythmias, moderate or worse valvular heart disease, myocardial infarction and heart failure. The secondary endpoint was overall survival, from EGFR-TKI initiation as first-line treatment to death from any cause.

“Despite the extended survival observed in patients with EGFR variations treated with Tagrisso compared with gefitinib or erlotinib, long-term outcomes may be compromised by significant cardiac risks,” study authors wrote. “Particularly given the high prevalence of EGFR variants (about 50%) in Asian populations.”

Reference:

“Cardiac Events and Survival in Patients With EGFR-Mutant Non–Small Cell Lung Cancer Treated With Osimertinib” By Dr. Chien-Yu Lin, et al. Jama Network Open.

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