Long-term survival of metastatic melanoma improves significantly with immunotherapy, clinical trial finds

Long-term data from a landmark international trial show that about half of patients with metastatic melanoma treated with a combination of immune checkpoint inhibitors survive cancer-free for 10 years or more, according to a new report from Weill Cornell Medicine and Dana-Farber Cancer Center researchers and colleagues.

The 10-year follow-up study, published September 15 in the New England Journal of Medicinewill end the Phase III CheckMate 067 trial. The trial, which followed 945 patients treated at 137 sites in 21 countries, demonstrated that the combination of nivolumab and ipilimumab, immunotherapies that inhibit two different immune checkpoint proteins, significantly improved outcomes in a disease that was almost universally fatal.

Subsequent analyses of patient outcomes three, five and six and a half years after the trial began demonstrated that the effect persisted for several years for patients who responded to treatment.

“This was a practice-changing trial,” said first author Jedd Wolchok, MD, Meyer director of the Sandra and Edward Meyer Cancer Center and professor of medicine at Weill Cornell Medicine and an oncologist at NewYork-Presbyterian/Weill Cornell Medical Center.

“The median survival for this population is now just over six years, and people who have no cancer progression after three years have a high probability of remaining alive and disease-free after 10 years.”

In 2011, the median survival for patients with metastatic melanoma was only six and a half months. However, the emergence of immune checkpoint inhibitors, which facilitate the immune system’s ability to attack cancer, as a treatment option has gradually begun to increase survival.

The CheckMate 067 trial demonstrated that nivolumab alone or in combination with another checkpoint inhibitor, ipilimumab, is a more effective approach than ipilimumab alone.

“This trial is a key part of how we talk to patients about the lasting benefits of immune checkpoint therapy and the potential for combining multiple immune therapies to improve treatment outcomes,” said F. Stephen Hodi, MD, director of the Melanoma Center and Center for Immuno-Oncology at Dana-Farber and co-senior author of the study. James Larkin, MD, of the Royal Marsden Hospital in the United Kingdom is the other co-senior author.

In addition to confirming long-term survival in about half of the patients treated with the combination, the 10-year analysis revealed no new safety concerns with the treatment. Some doctors had worried that treatment-related health problems might emerge later because patients must continue taking the drugs long term. But the 10-year analysis found no worrisome signs of long-term toxicity. There was also no resurgence of well-documented acute toxicities and few melanoma recurrences.

The team analyzed melanoma-specific survival and overall survival at 10 years and found that the two diverge in the long term, showing that metastatic melanoma survivors become increasingly likely to die of other causes as they age, an indication of long-term treatment success, the researchers said.

“After a decade of follow-up, we can now confidently tell our patients that there are treatments that can transform metastatic melanoma into a manageable disease in the long term, giving them confidence about the future,” said Dr. Hodi.

In addition to demonstrating a reassuring long-term efficacy and safety profile for this combination of immune checkpoint inhibitors, the researchers hope the data will also help improve care protocols for survivors of metastatic melanoma. The data suggest that patients who are still doing well after five or even three years are likely to continue doing well, which could allow doctors to reduce the frequency of follow-up visits or testing, they said.

These long-term data from the CheckMate 067 trial could help patients with metastatic melanoma understand their prognosis. Dr. Wolchok noted that patients are often understandably very frightened or depressed by the news that their cancer has spread.

“We’re trying to reorient them to an attitude of hope and more optimistic expectations,” he said. “We can now say that half of the patients treated with this combination therapy will live 10 years or more without fear of dying from metastatic melanoma.”