medwireNews: A secondary analysis of the CANTOS trial suggests that treatment with the interleukin-1β inhibitor canakinumab is associated with a reduced incidence of fatal cancers, lung cancer, and fatal lung cancers.
CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) was designed to investigate the efficacy of canakinumab in patients with atherosclerosis and persistent systemic inflammation who were stable after a myocardial infarction, the study authors explain in The Lancet.
Therefore, although the cancer endpoints were adjudged by a committee of oncologists blinded to allocation, the team emphasizes the need for replicating these exploratory data in formal settings of cancer screening and treatment.
Writing in a related comment, Brendan Jenkins (Hudson Institute of Medical Research, Clayton, Victoria, Australia) also urges caution in interpreting the “largely preliminary” findings.
Nevertheless, he believes that the data “make an important and timely contribution to the paucity of literature on the role of interleukin 1β in lung cancer.”
In the trial, 10,061 patients without a history of cancer and with a persistent pro-inflammatory response, as indicated by high-sensitivity C-reactive protein (hsCRP) levels of at least 2 mg/L, were randomly assigned to receive subcutaneous canakinumab at one of three doses – 50, 150, or 300 mg every 3 months – or placebo.
Over a median follow-up of 3.7 years, canakinumab use was associated with a significant reduction in total cancer mortality compared with placebo (hazard ratio [HR]=0.71). But further analysis by dose indicated this was restricted to patients in the 300 mg group (HR=0.49), with incidence rates per 100 person–years of 0.31 versus 0.64 in the placebo group.
This decrease appeared to largely be driven by significant reductions in the incidence of lung cancer (HR=0.33), at 0.16 versus 0.49 per 100 person–years in the 300 mg and placebo arms, respectively, and lung cancer mortality (HR=0.23), at 0.07 versus 0.30 per 100 person–years.
The incidence of lung cancer was also significantly lower in the canakinumab 150 mg than placebo group [HR=0.61], with respective rates of 0.30 and 0.49 per 100 person–years.
Canakinumab-treated patients were significantly more likely to experience fatal infections or sepsis than their counterparts given placebo, with an incidence rate per 100 person–years of 0.31 in the pooled canakinumab groups and 0.18 in the placebo group.
Looking to the future, lead author Paul Ridker (Brigham and Women’s Hospital, Boston, Massachusetts, USA) and fellow researchers believe that their data “warrant prospective assessment of canakinumab as a potential therapy for early lung cancers or after imaging-based lung-cancer screening, perhaps in combination with debulking procedures, radiation, and other immunomodulating treatments.”
The commentator on the other hand does not expect the CANTOS findings to directly inform lung cancer treatment, but “they do nonetheless shed light on interleukin 1β as a potential therapeutic target in lung cancer,” he writes.
“Further investigational studies should be done on the role of interleukin 1β in this malignancy.”
The study results were simultaneously presented at the 2017 European Society of Cardiology Congress, held in Barcelona, Spain.
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