Researchers have found that about 50% of patients with metastatic melanoma treated with a combination of nivolumab and ipilimumab experienced cancer-free survival of 10 years or longer, according to a recent study published by Wolchok et al in The New England Journal of Medicine.
Background
In 2011, the median survival among patients with metastatic melanoma was 6.5 months. However, the emergence of immune checkpoint inhibitors as a treatment option have begun to improve survival.
The CheckMate 067 trial demonstrated that nivolumab alone or in combination with ipilimumab may be a more effective treatment approach than ipilimumab alone. Nivolumab and ipilimumab are immunotherapies that inhibit two different immune checkpoint proteins.
“This trial is a key part of how we talk to patients about the lasting benefits of immune checkpoint therapy and the potential of combining multiple immune therapies to improve treatment outcomes,” explained co–senior study author F. Stephen Hodi, MD, Director of the Melanoma Center and the Center for Immuno-Oncology at Dana-Farber Cancer Institute.
Study Methods and Results
In the 10-year follow-up of the phase III CheckMate 067 trial, the researchers examined the long-term outcomes of 945 patients with metastatic melanoma who received a combination of nivolumab and ipilimumab at 137 sites across 21 countries.
Following subsequent analyses after 3, 5, and 6.5 years, the researchers discovered that the combination therapy significantly improved outcomes. The effect remained for several years in patients who responded to the treatment.
The researchers assessed melanoma-specific survival and overall survival at 10 years and revealed that the two diverge long term. For instance, metastatic melanoma survivors become increasingly likely to die of other causes as they age, an indication of long-term treatment success.
In addition to confirming long-term survival in about 50% of the patients who received the combination therapy, the 10-year analysis identified no new safety signals for the treatment. Although some physicians have expressed concern that treatment-related adverse events may emerge later, because patients must continue receiving the drugs long term, the 10-year analysis found no concerning signals of long-term toxicity. There was also no resurgence of well-documented acute toxicities and few recurrences of melanoma.
“This was a practice-changing trial,” emphasized lead study author Jedd Wolchok, MD, PhD, Professor of Medicine and the Meyer Director of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine as well as an oncologist at NewYork–Presbyterian/Weill Cornell Medical Center. “The median survival for this population is now a little over 6 years, and [patients] who are free from cancer progression at 3 years have a high likelihood of remaining alive and disease-free at the 10-year time point,” he added.
Conclusions
“After a decade of follow-up, we can now confidently tell our patients there are treatments available with the potential to transform metastatic melanoma into a manageable, long-term condition, instilling confidence about the future,” highlighted Dr. Hodi.
After demonstrating a long-term efficacy and safety profile for this immune checkpoint inhibitor combination, the researchers hope the data will also help improve the care protocols for metastatic melanoma survivors. The findings suggested that patients who are still responding at 5 or even 3 years are likely to continue doing well, which may allow physicians to reduce the frequency of follow-up visits or tests. Additionally, the long-term data from the CheckMate 067 trial may help patients with metastatic melanoma better understand their prognosis.
“We try to reorient them toward an attitude of hope and more optimistic expectations,” Dr. Wolchok noted. “We can now say [50%] of patients treated with this combination therapy will live 10 years or longer without the concern of dying from metastatic melanoma,” he concluded.
Disclosure: The research in this study was funded by Bristol Myers Squibb, the National Cancer Institute, and the National Institute for Health Research Royal Marsden–Institute of Cancer Research Biomedical Research Centre. For full disclosures of the study authors, visit nejm.org.
