t was big news earlier this summer when a groundbreaking study of 10,000 patients found that an anti-inflammatory drug significantly reduced the risk of cardiovascular complications in heart attack survivors. Now, the researchers have found that the drug had a surprising (and welcome) side effect: It also sharply cut the rates of lung cancer.
Lead investigator Dr. Paul Ridker of Brigham and Women’s Hospital showed that the biologic drug canakinumab from Novartis (NVS) — which has thus far only been approved to treat a rare disease — lowered the incidence of cardiovascular complications by 15 percent. This fits in line with his original hypothesis: That by targeting an inflammatory pathway seen in heart disease, one could lower the risk for heart attack, stroke, and cardiovascular death.
But he built in a second arm to the global, four-year study to examine if this anti-inflammatory drug might impact cancer risk as well. Those results came out Sunday morning, and they showed a clear pattern:
Among patients who were given the lowest dose of canakinumab, lung cancer rates dropped 26 percent. A medium dose led to a 39 percent decline in lung cancer. And the highest dose decreased incidence by a startling 67 percent. Patients who received this highest dose also had about half the rate of overall cancer death, compared to those who received a placebo.
STAT chatted with Ridker about his study — and his interpretation of the findings. Here’s an excerpt:
Why did you want to tack on a cancer study in this large-scale heart disease trial?
I’m obviously an inflammation biologist, interested in the inflammatory pathways of atherosclerosis. However, when we designed this study back in 2009, we knew full well that there was a whole other piece of biology that we might be able to help with. This NLRP3 pathway that we study increases your risk of other kinds of cancers, including non-small cell lung cancer.
If you’re a long-haul truck driver inhaling diesel fuel all day, or working in a shipyard — all of these things are chronically inflaming your lungs, and all are known to increase the risk of lung cancer. It’s also been hypothesized that inflammation of the tumor microenvironment plays a role in the growth and metastases of tumors — though not necessarily triggering the tumor to grow in the first place.
So we decided the day the trial started not only to have a cardiovascular endpoint committee, but an oncology endpoint committee — in which a group of oncologists have been classifying all the cancers that occurred in the study. And we had some particular suspicions about lung cancer.
Why lung cancer in particular?
We set this trial up in patients with prior heart attack, but no prior history of cancer. Patients who have prior heart attack are very likely to have smoked cigarettes — and I knew, because I’m an inflammation researcher, that they’re also at a high risk for lung cancer. So this particular study — though set up for atherosclerosis — turns the way people look at oncology upside down.
How do you mean?
It takes people with severe refractory disease who are at a high risk for some cancers — but none knew they had cancer. It’s a randomized trial, in 10,000 middle-aged people around the globe. Some have undiagnosed lung, breast, prostate cancer — whatever. But because it’s randomized, we know the risk factor equally distributed into four arms of the trials.
So we knew that while doing the atherosclerosis study, we were going to have a very elegant mechanism to address whether or not inflammation inhibition would impact future risk for cancer. That was baked into the protocol.
And as the Lancet paper describes, we had a remarkable result — with a dramatic reduction in cancer mortality.
But you warn some caution about these results all the same, right?
The reason we have to be careful about this: It’s very exploratory, and needs to be confirmed. And while the biology is obviously very exciting and makes a lot of sense, it’s not yet clear how one would translate that into treatment algorithms for someone who already has lung cancer.
We think there was already some distribution of underlying, as-yet-undiagnosed cancers — and by giving anti-inflammatory drugs, we appear to have slowed the growth and invasiveness of these cancers. So people have survived longer on canakinumab.
This is the first human data for an intervention like this, saying we can intervene in that inflammation, and get a better clinical outcome. So that’s why we’ve flipped oncology on its head.