In Stage 4 Melanoma, Among Every 2 Patients One Achieved at Least 5 Years of Survival with Combined Immunotherapy

Stage 4 malignant melanomahas seen disappointment turn to hope through an immunotherapy study whose results were presented at ESMO 2019 and published simultaneously in NEJM. Whereas 10 years ago, among 20 patients only one reached 5-year survival, nivolumab (Opdivo) + ipilimumab (Yervoy) Combined immunotherapy raising this above 50% brought joy to us all. At ESMO 2019, new survival data from CheckMate 067 were presented.

This is a major advance in the history of cancer ! Nivolumab plus ipilimumab is important in clinical practice not only for melanoma, but also for kidney cancer and certain types of colon cancer patients.

A Fundamental Change in Advanced Melanoma Treatment

Ipilimumab (Yervoy) received FDA approval in 2011 as the first immune checkpoint type of cancer immunotherapy. In 2014, pembrolizumab (Keytruda) and nivolumab (Opdivo) were approved with greater efficacy and fewer side effects. This important advance was also the subject of the 2018 Nobel Prize in Medicine. Now, awaited long-term results of nivolumab plus ipilimumab demonstrate "fantastic progress" for melanoma and other cancers.

The combination is more potent than nivolumab or pembrolizumab alone, with higher response rates and more side effects. However, there is no established method to predict who will benefit most. Decisions should be made with patients and families, using oncologist experience and considering special circumstances such as brain metastases.

CheckMate 067 Results

CheckMate 067 enrolled metastatic melanoma patients, numbering 945, randomized into 3 arms:

• ipilimumab and nivolumab 314 patients,
• nivolumab alone 316 patients and
• ipilimumab alone 315 patients.

The 5-Year Overall Survival Rates Were 52% for Nivolumab Plus Ipilimumab, 44% for Nivolumab and 26% for Ipilimumab.

Other findings were:

• The 5-year progression-free survival rate was 36% for the combination, 29% for nivolumab alone and 8% for ipilimumab alone.
• The objective response rate was 58% with combination treatment, 45% with nivolumab alone and 19% with ipilimumab alone.
• The treatment-free intervalis an important outcome for patients.

For patients receiving combined immunotherapy, the treatment-free interval was the longest:

• 18.1 months with the combination, 1.9 months with nivolumab alone and 1.8 months with ipilimumab alone.
• Three-quarters (74%) of combination-treated patients were alive and treatment-free after 5 years, significantly higher than 58% receiving nivolumab alone and 45% receiving ipilimumab alone.
• The authors reported no new safety signals (side effects) or treatment-related deaths after 5 years.

Activity Against Brain Metastases

Nivolumab plus ipilimumab is the preferred approach particularly for melanoma with brain metastases. Brain metastasis response was 51% with combination treatment versus 20% with nivolumab alone. Complete and partial response rates were also higher with the combination. Complete and partial responses with nivolumab were 16% and 4%, respectively, versus 26% and 26% with the combination. Three-year brain metastasis progression-free survival was 43% with the combination and 15% with nivolumab alone.

In conclusion, immunotherapies have indisputably changed oncology’s destiny in less than 10 years. Much remains to achieve more satisfying outcomes, but melanoma has most clearly demonstrated the long-term, lasting results of this new drug group.