TreatmentUpdate
223

December 2017 

Canakinumab’s anti-cancer potential

Canakinumab is an antibody that is used to treat rare inflammatory conditions. It works by interfering with a receptor for the chemical signal interleukin-1b (IL-1b). IL-1b binds to this receptor found on the surface of many cells. By binding to this receptor, a reaction is triggered; if sustained, it leads to inflammation. Research increasingly suggests that inflammation likely plays some role in the development, growth and possibly the spread of cancer within the body.

In a study called Cantos, researchers investigated the ability of canakinumab to reduce inflammation linked to serious cardiovascular disease and cancer. Their rationale for this was that “patients with atherosclerosis commonly smoke, which is a risk factor for cancer.” For this study, researchers recruited more than 10,000 HIV-negative participants at high risk for major cardiovascular events (heart attack, stroke). About 67% of participants had previously undergone cardiovascular procedures/surgery, about 71% were either past or current smokers, and at least 80% were taking medicines to reduce blood pressure, lower abnormal lipids, reduce blood clotting and so on. All participants had elevated levels of inflammation. Participants were randomly assigned to receive one of several doses of canakinumab (50, 150 or 300 mg) or placebo once every three months, via injection under the skin.

After an average of 3.7 years in the study, participants on canakinumab experienced significantly reduced inflammation and heart attacks compared to those taking placebo. Also, overall, there were fewer cases of cancer (principally lung cancer) among canakinumab users compared to placebo users. A significant decrease in new cases of cancer occurred only in participants who received the 300-mg dose of canakinumab. Researchers found that deaths due to complications from infections was more common among canakinumab users, but these deaths were more or less balanced by a reduction in deaths from complications of lung cancer.

The Cantos study was primarily designed to assess the cardiovascular benefit of canakinumab. Its anti-cancer effect, while promising, should be considered preliminary. Clinical trials specifically designed to explore canakinumab’s anti-cancer potential are now needed, particularly in the field of lung cancer.

Study details

Please see the previous report for the full details of the Cantos study.

Results—Who was diagnosed with cancer?

During the study, people with the following characteristics were more likely to be diagnosed with cancer:

  • older people
  • current smokers

Inflammation and cancer

Previous studies have found a link between inflammation and cancer. Specifically, elevated levels of the chemical signal IL-6 (interleukin-6) and high-sensitivity C-reactive protein (hsCRP) in the blood have been linked to heightened inflammation. Participants who entered the Cantos study with higher-than-average levels of inflammation markers (IL-6, hsCRP) were more likely to subsequently develop cancer. For instance, people who had high levels of hsCRP (6.0 mg/litre vs. 4.2 mg/litre) were more likely to develop cancer. A similar pattern was seen with IL-6: People who entered the study with relatively high levels of IL-6 (3.2 ng/litre vs. 2.6 ng/litre) were more likely to develop cancer.

These differences in the risk of cancer diagnosis between high and low levels of hsCRP and IL-6 were statistically significant.

Inflammation and canakinumab

Participants who received canakinumab had significant reductions in hsCRP (between 26% and 41%) and in IL-6 (between 25% and 43%) compared to people on placebo. These differences between canakinumab and placebo were statistically significant.

Survival and cancer

Overall, participants who received canakinumab were less likely to die from cancer-related complications. The greatest difference in death rates was seen in people who received canakinumab 300 mg vs. placebo. This difference was mainly due to a reduction in deaths from complications of lung cancer among canakinumab users.

The distribution of cancers and cancer-related deaths was as follows:

Placebo

  • 26% of all cancers were lung cancers
  • 47% of all deaths due to cancer arose from lung cancer

Canakinumab

  • 16% of all cancers were lung cancers
  • 34% of all deaths due to cancer arose from lung cancer

Researchers found that the effect of canakinumab on lung cancer was “slightly stronger in current than past smokers.” This was most noticeable in people who received the 300-mg dose of canakinumab.

Inflammation and cancer

Researchers noted that rates of lung cancer did not differ significantly between participants who received canakinumab or placebo who had levels of hsCRP greater than 1.8 mg/litre at the third month of the study. A similar effect was seen with participants whose IL-6 levels were greater than 1.64 ng/litre at the third month of the study. These findings suggest that some participants whose inflammation was not sufficiently reduced by canakinumab did not experience its anti-cancer effect. It may be that there is a subgroup of people who do not fully respond to canakinumab. This idea will require further study.

Adverse events

The term adverse events is used to describe a range of unfortunate incidents that can occur in a clinical trial. Only some of these events are caused by the study medicine. As Cantos was a placebo-controlled study, researchers have a good idea of which side effects canakinumab had. The main ones were as follows:

Neutropenia

  • lower-than-normal levels of neutrophils in the blood (neutrophils are important cells that help control infections)

Infections

When the researchers reviewed data from all three groups of participants who received different doses of canakinumab, they found that there were significantly more deaths from complications of infections in people on canakinumab than those on placebo. Why this happened is not clear; the study authors did not link these deaths to lower-than-normal levels of neutrophils. According to the researchers, “the patients who died from infections tended to be older and more likely to have diabetes than those who did not die from infection.”

—Sean R. Hosein

REFERENCE:

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. Lancet. 2017 Oct 21;390(10105):1833-1842.