Treatment that targeted inflammation in the postmyocardial infarction (post-MI) setting led to a thought-provoking reduction in lung cancer incidence and mortality, according to a safety analysis of a large randomized trial.
Patients treated with the interleukin inhibitor canakinumab (Ilaris) had significantly lower total cancer incidence and cancer mortality versus placebo. The overall results included a 67% reduction in lung cancer incidence and a 77% reduction in lung cancer mortality in patients who received the highest of three canakinumab doses, reported Paul M. Ridker, MD, of Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues.
The hypothesis-generating data added to evidence that inflammation has a role in the evolution and progression of cancer.
“Chance is a possible explanation for our findings, but is unlikely in view of the biological mechanisms and highly significant associations reported,” the authors wrote. “The randomized nature of our trial also greatly reduces, but does not eliminate the potential for confounding.”
The study “confirms by intervention what we have long suspected on the basis of observational studies and laboratory experiments,” said Larry Norton, MD, of Memorial Sloan Kettering Cancer Center in New York City. “Cancer is not a disease of the cancer cells alone. The relationships between cancer cells and their microenvironment — including inflammatory leukocytes — is critical. We know that some leukocytes can be cancer fighting under the right conditions, but some can be procarcinogenic too, a true yin-yang situation.”
Malignancies often occur in or near chronically inflamed tissue, and inadequate resolution of inflammation has been hypothesized as a potentially major contributor to cancer invasion, progression, and metastasis, the authors noted. Inflammation has particular relevance to lung cancer because chronic bronchitis arising from external inhaled toxins is associated with a persistent inflammatory response.
The trial involved 10,061 patients in stable condition following MI, randomized to placebo or to one of three doses of canakinumab (50, 150, or 300 mg). The primary objective was to determine whether inhibition of IL-1β with canakinumab would reduce the incidence of recurrent events (nonfatal MI, nonfatal stroke, and cardiovascular death) in patients with a persistent proinflammatory response, as defined by elevated high-sensitivity C-reactive protein.
Eligible patients had to be cancer free at enrollment, and the safety analysis included follow-up for cancer. During a median follow-up of 3.7 years, 685 patients developed cancer, including 129 lung cancers.