Canakinumab’s effect on lung cancer

An exploratory analysis of the CANTOS data, which was published in The Lancet, also showed that canakinumab reduced the rates of total cancer death, particularly death due to lung cancer, and the incidence of lung cancer.


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During a median follow-up of 3.7 years, canakinumab was associated with dose-dependent reductions in concentrations of hsCRP of 26% to 41% and of interleukin 6 of 25% to 43%, compared with placebo. Total cancer mortality (n=196) was significantly lower in the pooled canakinumab group than in the placebo group, but individually was significantly lower than placebo only in the 300-mg group (hazard ratio [HR], 0.49). Incident lung cancer (n=129) was significantly less common in the 150-mg group (HR, 0.61) and 300-mg groups (HR, 0.33). Lung cancer mortality was significantly less frequent in the canakinumab 300-mg group than in the placebo group (HR, 0.23) and in the pooled canakinumab group than in the placebo group.

“Our hypothesis-generating data suggest the possibility that anti-inflammatory therapy with canakinumab targeting the interleukin-1β innate immunity pathway could significantly reduce incident lung cancer and lung cancer mortality,” stated Dr Ridker and colleagues. “Replication of these data in formal settings of cancer screening and treatment is required.”

A step forward, but caution urged

In an accompanying editorial published in the New England Journal of Medicine, Robert A. Harrington, MD, from the Department of Medicine at Stanford University, noted that although the CANTOS trial has helped move the inflammatory hypothesis of coronary artery disease forward, barriers remain before canakinumab can be used routinely for this purpose.

“Despite the scientific and clinical excitement associated with having a new mechanism of action to attack in the treatment of coronary artery disease, a better understanding of the risks and benefits of this form of therapy is needed,” stated Dr Harrington. “Any discussion of the use of canakinumab in patients with a previous myocardial infarction must consider cost. Given monthly for approved indications, canakinumab is priced at approximately $200,000 per year in the United States. Such pricing may be suitable for rare diseases, but not for a common indication such as coronary artery disease, even if given every 3 months.

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“Now that an agent targeting inflammation and autoimmunity has been shown to provide clinical benefit, the field is opened to further investigation to find agents that exert more substantial benefit than was seen in CANTOS and perhaps to find agents that do not increase the risk of death from infection as was seen with canakinumab,” Dr Harrington concluded.

References

  1. Harrington RA. Targeting inflammation in coronary artery disease [published online August 27, 2017]. N Engl J Med.  doi: 10.1056/NEJMe1709904
  2. Ridker PM, MacFadyen JG, Thuren T, Everett BM, Libby P, Glynn RJ,  on behalf of the CANTOS Trial Group. 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: h10.1016/S0140-6736(17)32247-X
  3. Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease [published online August 27, 2017]. N Engl J Med. doi: 10.1056/NEJMoa1707914