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 follow-up data from CheckMate -067 presented at the European Society for Medical Oncology (ESMO) Congress 2024 in Barcelona, Spain and simultaneously published in The New England Journal of Medicine.
At 10 years, 43% of patients treated with nivolumab (Opdivo, Bristol Myers Squibb) plus ipilimumab (Yervoy, Bristol Myers Squibb) were alive. By contrast, a decade ago, this patient population faced a survival rate of around 25% after only one year.
“This was a practice-changing trial,” says first author Jedd Wolchok, MD, PhD, the 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 in New York City, in a news release. “The median survival for this population is now a little over six years, and people who are free from cancer progression at three years have a high likelihood of remaining alive and disease-free at the 10-year time point.”
The 10-year follow-up study concludes the phase 3 CheckMate 067 trial. The trial, which followed 945 patients treated at 137 sites in 21 countries, demonstrated that combining nivolumab plus ipilimumab dramatically improved outcomes for a condition that had been nearly universally fatal. Subsequent analyses of patient outcomes at 3-, 5-, and 6.5 years after the trial launched demonstrated that the effect persisted for several years for patients who responded to the treatment.
In 2011, the median survival for patients with metastatic melanoma was just six and a half months. However, the emergence of immune checkpoint inhibitors as a treatment option gradually increased survival. The CheckMate 067 trial demonstrated that nivolumab alone or combined with another checkpoint inhibitor, ipilimumab, is more effective than ipilimumab alone.
With a minimum follow-up of 10 years, the median overall survival (OS) was 71.9 months with nivolumab plus ipilimumab—the longest reported median OS in a Phase 3 advanced melanoma trial—36.9 months with nivolumab and 19.9 months with ipilimumab.
Among all randomized patients in the trial, 64% of patients who received the combination, 50% of nivolumab-treated patients, and 33% of ipilimumab-treated patients did not receive subsequent systemic therapy at the 10-year follow-up mark.
In addition, at 10 years of follow-up, the nivolumab plus ipilimumab combination showed melanoma-specific survival (MSS) rates of 52% (median not reached) compared to 44% (median of 49.4 months) and 23% (median of 21.9 months) among patients treated with nivolumab alone and ipilimumab alone, respectively.
Durable, sustained clinical benefit was also observed with nivolumab plus ipilimumab or nivolumab alone across relevant subgroups, including in patients with BRAF mutation and wild-type tumors. Among patients with BRAF-mutant tumors, the rate of OS at 10 years was 52% in patients who received nivolumab plus ipilimumab, 37% for nivolumab alone, and 25% for ipilimumab alone. In patients with BRAF wild-type tumors, the rate of OS at 10 years was 39% in patients who received nivolumab plus ipilimumab, 37% for nivolumab alone, and 17% for ipilimumab alone.
At 10 years of follow-up, the objective response rate (ORR) was higher for the two nivolumab groups, in combination with ipilimumab and alone, at 58.3% and 44.9%, respectively, than for the ipilimumab group, at 19.0%. The median duration of response (DoR) was not reached for those who received nivolumab plus opilimumab, while the median DoR was 103.2 months for nivolumab-treated patients and 19.2 months for ipilimumab-treated patients.
The safety profile for nivolumab plus ipilimumab was consistent with prior findings, with no new safety signals observed and no additional treatment-related deaths occurring since the prior three analyses. Grade 3/4 treatment-related adverse events were reported in 62.6% of patients in the combination group, 24.6% of patients in the nivolumab group, and 29.6% of patients in the ipilimumab group.
“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,” adds F. Stephen Hodi, MD, the director of the Melanoma Center and the Center for Immuno-Oncology at Dana-Farber in Boston and the co-senior author of the study.
“After a decade of follow-up, we can now confidently tell our patients that there are treatments available with the potential to transform metastatic melanoma into a manageable, long-term condition, instilling confidence about the future.”
In addition to demonstrating a reassuring long-term efficacy and safety profile for this immune checkpoint inhibitor combination, the investigators hope the data will also help improve the care protocols for metastatic melanoma survivors. The data suggest that patients still doing well at five or even three years are likely to continue doing well, which may allow physicians to reduce the frequency of follow-up visits or tests, the researchers note.
These long-term data from the CheckMate 067 trial may help patients with metastatic melanoma understand their prognosis. Dr. Wolchok notes that patients are often understandably very afraid or depressed by the news that their cancer spread.
“We try to reorient them toward an attitude of hope and more optimistic expectations,” he said. “We can now say half of patients treated with this combination therapy will live 10 years or longer without the concern of dying from metastatic melanoma.”
PHOTO CAPTION: Jedd Wolchok, MD, PhD
PHOTO CREDIT: Weill Cornell Medicine
