Impact of Canakinumab on Mortality, Incidence of Lung Cancer
Patients in the canakinumab groups experienced an overall significant reduction in total cancer mortality.
Patients who receive anti-inflammatory therapy with canakinumab, a human monoclonal antibody that targets interleukin-1β, may have a decreased rate of incident lung cancer and lung cancer mortality, according to a study published in The Lancet.1
Activation of the Nod-like receptor protein 3 inflammasome in the lungs leads to production of active interleukin-1β, a contributing factor to chronic fibrosis and lung cancer.
Researchers for the phase 3 CANTOS trial (ClinicalTrials.gov Identifier: NCT01327846), enrolled 10,061 patients with atherosclerosis who had myocardial infarctions and investigated the effect of canakinumab in preventing recurrent vascular events. Patients were eligible for the study if they did not have a history of cancer and had a blood concentration of 2 mg/L of high-sensitivity C-reactive protein (hsCRP), a marker of inflammation.
In a secondary analysis of the CANTOS trial, researchers analyzed the effect canakinumab's inhibition of interleukin-1β may have on the risk of cancer.
Patients who were ultimately diagnosed with lung cancer had significantly higher baseline concentrations of hsCRP (median 6.0 mg/L vs 4.2 mg/L; P <.0001) and interleukin-6 (3.2 ng/L vs 2.6 ng/L; P <.0001) compared to patients who were not.
During the median follow-up of 3.7 years, patients who received canakinumab 150 mg or 300 mg experienced dose-dependent reductions in concentrations of 26% to 41% of hsCRP and 25% to 43% of interleukin-6 concentrations compared to placebo (P <.0001).
Incident lung cancer occurred at significantly lower rates in the 150 mg group (HR, 0.61; 95% CI, 0.39-0.97; P =.034) and the 300 mg group (HR, 0.33; 95% CI, 0.18-0.59; P <.0001).
Patients in the canakinumab groups experienced an overall significant reduction in total cancer mortality (P =.0007), but only the 300 mg group achieved significantly lower total cancer mortality compared to placebo (hazard ratio [HR], 0.49; 95% CI, 0.31-0.75; P =.0009).
Lung cancer mortality was significantly less common in the 300 mg group (HR, 0.23; 95% CI, 0.10-0.54; P =.0002) compared to placebo.
The study authors concluded by saying that these “exploratory data should be replicated and extended in settings directly related to early cancer screening and initial treatment of cancers, particularly lung cancer.”
Ridker PM, MacFadyen JG, Thuren T, et al. Effect of interleukin-1β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial [published online August 27, 2017]. Lancet. doi: 10.1016/S0140-6736(17)32247-x