The rationale for the study that I had the privilege of presenting at ASCO was a long-term follow-up of a phase III randomised trial in patients with newly-diagnosed metastatic melanoma who were treated initially with either ipilimumab to block CTLA-4, nivolumab to block PD-1, or the combination. This was a study that was initially reported at ASCO in 2015, met its primary endpoint then in terms of progression-free and overall survival for the two nivolumab-containing groups being superior to ipilimumab. Now we are looking at long-term survival outcomes with 6.5 years of follow-up.
This was a placebo controlled, double-blind randomised clinical trial which has subsequently been unblinded, but this was ongoing follow-up out with a minimum now of 6.5 years.
The key findings were several: first of all there was no change in the safety profile for the study; there was no significant change in the response rate; there was a sustained improvement in overall survival for the two nivolumab-containing groups compared with the ipilimumab-containing group, now extending out to 6.5 years of follow-up. Importantly, for the first time, we were able to calculate a median overall survival for the patients initially treated with the combination of ipilimumab and nivolumab, and now that median has been estimated at 72.1 months.
In this current analysis also we also presented melanoma-specific survival. In that context, again with 6.5 years follow-up, the median of melanoma-specific survival for the combination group has not been reached.
What these results allow us to do as clinicians is to discuss the durability of the initial responses with patients. They give us further experience with which to share with patients and their families when we try to choose between single-agent PD-1 blockade and combination blockade. They also provide an important reference set with long-term survival outcomes in a large, global clinical trial that can provide important context as new immunotherapies such as relatlimab in combination with nivolumab enter later-stage clinical testing.
