CANTOS: Decades of Research Culminate in Landmark Findings
Paul Ridker
Paul M. Ridker, MD, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital, and colleagues presented landmark research this week suggesting that an anti-inflammatory drug can significantly reduce recurrent heart attacks and lower the risk of lung cancer among certain high-risk individuals.
Ridker and colleagues reported their findings from the CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) trial, which was designed to test whether reducing inflammation among people who have had a prior heart attack can reduce their risk of another cardiovascular event happening in the future. Results were presented at the European Society of Cardiology meeting and published simultaneously in the New England Journal of Medicine and The Lancet this week.
More than 10,000 patients with a history of heart attacks who had high levels of C-reactive protein (hsCRP) – a biomarker of inflammation – were enrolled in the study. None of the participants had been diagnosed with cancer when the trial began.
Reducing Inflammation Without Lowering Cholesterol Cuts Risk of Cardiovascular Event
Ridker and colleagues reported CANTOS findings show a significant reduction in risk of recurrent heart attacks, strokes and cardiovascular death among participants who received a targeted anti-inflammatory drug that lowered inflammation but had no effects on cholesterol. These findings are detailed in a paper published simultaneously in the New England Journal of Medicine.
“These findings represent the end game of more than two decades of research, stemming from a critical observation: Half of heart attacks occur in people who do not have high cholesterol,” said Ridker. “For the first time, we’ve been able to definitively show that lowering inflammation independent of cholesterol reduces cardiovascular risk. This has far-reaching implications. It tells us that by leveraging an entirely new way to treat patients – targeting inflammation – we may be able to significantly improve outcomes for certain very high-risk populations.”
Peter Libby, MD, a BWH cardiovascular specialist, worked on the scientific foundation of CANTOS, postulating a role for interleukin-1 in atherosclerosis in 1986, and worked with Ridker to help launch the trial.
“CANTOS represents a milestone in a long journey implicating interleukin-1 in cardiovascular disease,” said Libby. “The results not only establish the role of innate immunity in human atherosclerosis and make actionable decades of research, but they also usher in a new era of therapeutics.”
Read “Anti-Inflammatory Therapy with Canakinumab for Atherosclerotic Disease” in the New England Journal of Medicine.
Anti-Inflammatory Therapy Cuts Risk of Lung Cancer
In addition to the compelling findings on inflammation and cardiac event risk, discoveries from the CANTOS trial have also given researchers a unique opportunity: to explore the effectiveness of giving a drug to patients before cancer emerges. Ridker and colleagues shared that patients who received the anti-inflammatory therapy canakinumab had a dramatic reduction in incidence of lung cancer and lung cancer mortality. In this high-risk population, death from cancer was reduced by half in the group of people who received the highest dosage of the drug. These findings are detailed in a paper published simultaneously in The Lancet.
“Our work builds on the idea that cancer and inflammation are intimately linked, and gives novel insights regarding how inhibiting inflammation may slow cancer progression and invasiveness,” said Ridker. “While confirmatory work in formal cancer studies are needed to address if and how canakinumab can be integrated into lung cancer protocols, this work represents a stepping stone toward what we hope will be a new treatment approach.”
“These are fascinating, human findings that open a potential new class of therapies for cancer,” said Laurie H. Glimcher, MD, president and CEO of Dana-Farber Cancer Institute, who was not involved in the study. “We look forward to working with Dr. Ridker and his colleagues to develop and further evaluate anti-inflammatory therapies for lung cancer.”
Ridker noted that multinational studies such as CANTOS are “a true team effort.”
“In addition to the 1,000 physicians worldwide who enrolled patients for us, a very special thanks is due to Professor Robert Glynn, Ms. Jean MacFadyen and Dr. Brenden Everett – three outstanding Brigham scientists without whom the trial would not have succeeded,” he said.
Read “Effects of Interleukin-1 Inhibition with Canakinumab on Incident Lung Cancer in Patients with Atherosclerosis: Exploratory Results from a Randomized Double-blind Placebo Controlled Trial” in The Lancet.