Thromboembolism incidence in NSCLC varies greatly by molecular subtype
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Patients with anaplastic lymphoma kinase-mutant non-small cell lung cancer exhibited considerably higher risk for thromboembolism than those with EGFR-mutant or wild-type disease, study results showed.
Thromboembolism appeared associated with shorter survival regardless of molecular subtype, according to the findings, published in Journal of Thrombosis and Haemostasis.
“We were surprised by the very high rates of venous thromboembolism associated with ALK-mutant disease,” researcher Alok A. Khorana, MD, professor of medicine at Cleveland Clinic Lerner College of Medicine, told Healio. “Despite treatment options transitioning away from chemotherapy, patients with lung cancer remain at high risk for VTE. Patients should be made aware of warning signs and symptoms of disease, and appropriate patients should have a discussion of [risks vs. benefits] of thromboprophylaxis as discussed in the latest ASH and ASCO guidelines.”
Thromboembolism is common among patients with NSCLC, and this condition is associated with poorer outcomes.
The identification of molecular subtypes of NSCLC has led to the development of effective targeted treatments. However, the association of common NSCLC subtypes — such as anaplastic lymphoma kinase (ALK)-mutant or EGFR-mutant disease — and thromboembolism had not been established.
“As treatment options for lung cancer evolve and patients are surviving longer with molecularly targeted therapy, we wanted to study how the incidence [and] prevalence of VTE has evolved, as well,” Khorana said.
Khorana and colleagues conducted a retrospective cohort study of 461 consecutive patients (57% female; 58% aged older than 65 years) with NSCLC for whom molecular classification and follow-up were available. All patients were seen at Cleveland Clinic between July 2002 and July 2017.
Researchers calculated incidence of thromboembolism events, including deep vein thrombosis, pulmonary embolism, visceral vein thrombosis and arterial events.
Investigators used the Kaplan-Meier method to estimate thromboembolism-free survival and OS rates for patients with ALK-mutant (n = 46), EGFR-mutant (n = 165) and wild-type (n = 250) disease. They used Cox proportional hazard regression analyses to identify factors associated with thromboembolism and OS.
Median follow-up was 33.1 months.
Ninety-eight patients (21.3%) developed thromboembolism. Researchers reported the highest thromboembolism rate among patients with ALK-mutant NSCLC (43.5%; n = 20), followed by EGFR-mutant disease (21.2%; n = 35) and wild-type disease (17.2%; n = 43). The difference reached statistical significance (P < .05).
Cumulative thromboembolism incidence at 6 months also was higher among those with ALK-mutant cancers (15.7%; 95% CI, 5-26.4) than those with EGFR-mutant cancers (8.8%; 95% CI, 4.4-13.2) or wild-type disease (9.2%; 95% CI, 5.4-12.9).
More research is required to determine why thromboembolism incidence appeared so much higher among patients with ALK-mutant disease, Khorana said.
“One obvious answer could be that, given the prolonged survival associated with targeted agents for patients with ALK-mutant lung cancer, the high rates simply reflect longer survival (ie, exposure time to [the] drug is longer than with standard chemotherapy),” Khorana told Healio. “However, this is less likely given that we also observed very high rates at defined time intervals (eg, 6 months from diagnosis).”
In the overall cohort, patients who developed thromboembolism achieved significantly shorter OS (HR = 2.8; 95% CI, 2.1-3.6).
The pathophysiologic mechanisms underlying the association of VTE with lung cancer, as well as its impact on OS, will be key questions to address in future research, Khorana said.
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