Checkmate 067 - combined nivolumab and ipilimumab

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Published: 12 Apr 2017
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Dr Suzanne Topalian - Sidney Kimmel Comprehensive Cancer Center, Baltimore, USA

Dr Topalian speaks with ecancer at AACR 2017 about the combination of ipilimumab and nivolumab for advanced melanoma.

The results were presented at the conference by Dr James Larkin, and Dr Topalian comments on the response rates and overall survival in the combination.

She considers the prospective value of BRAF and PD-1 biomarkers, and notes a significant increase in trial discontinuation due to adverse events.

The combination of nivolumab and ipilimumab is the first regulatory approved combination in immunotherapy of any kind. It’s approved specifically for patients who have advanced melanoma. The components of this therapy were individually approved in past years, so ipilimumab by itself can be effective in a certain number of patients with advanced melanoma; it provides by itself a 20% long-tern survival benefit. Nivolumab by itself can be effective, either as the first treatment or later treatment that a patient with melanoma might receive. There the overall survival benefit is greater, it’s more at the 30% or 35% level. So the intriguing question is what happens if you combine these two drugs that are in the same class because they both target immune checkpoints in cancer but they work by different mechanisms. So laboratory evidence showed that they could be complementary and have a synergistic impact if used together.

What we saw today were long-term results of a randomised trial where patients who had never been treated before for their advanced melanoma received either ipilimumab alone, nivolumab alone or the drug combination. This was a very large trial, almost 1,000 patients, a global trial. One definite result from this trial is that either nivo alone or the combination therapy has a much greater impact than ipilimumab, which was the older therapy, if used by itself. So we saw that in terms of response rates and also in terms of overall survival with years of follow-up now.

Another question that’s really on everybody’s minds is the comparison between nivolumab by itself and the combination with ipilimumab. There, unfortunately, this study was not designed or powered to look directly at that combination. So any of the comparisons that we saw today were descriptive comparisons and not supported by statistical analysis. Nevertheless, it looked as if there might be subgroups of patients where the benefit of the combination was more apparent and we talked about that in terms of perhaps patients with BRAF mutant melanomas might benefit more from the combination than from nivolumab alone. The role of PD-L1 expression, the PD-L1 biomarker, tantalising but not definitive in this study.

All of that needs to be balanced against the safety profile of the combination versus the monotherapies where it’s clear that the combination does have an increased risk of side effects and a higher proportion of serious side effects with a greater number of patients having to stop the treatment because of side effects. So, as with every other area of oncology, we’re always thinking about risk and benefit and what you heard from Dr Larkin is that it really boils down to thinking about each patient individually and what their medical profile is and what would be the right approach for them.