Dr John Kirkwood discusses physician considerations that are examined before immunotherapy use in the treatment of melanoma.
Matthew Fowler: What are some of the considerations for use of immunotherapy in patients with melanoma?
John Kirkwood, MD, PhD: In the metastatic disease setting, the sites of disease that the patients have are often a cardinal consideration with respect to pursuit of therapy. In patients who have, for instance, brain metastatic disease, the combination of ipilimumab and nivolumab, CTLA-4/PD-1 blockade, has been shown to have similar benefits in patients with brain disease to the benefits that we’ve seen in peripheral non-CNS [central nervous system] disease. That has nudged us all to consider the original doublet, ipilimumab/nivolumab, in the treatment of any patients who have brain disease where the presence of 1 site of brain disease often implies the risk for additional sites that may need to be treated.
In Pittsburgh we have had the benefit of a very effective but focal therapy of disease, what is called stereotactic radiosurgery [SRS], which has the ability to obliterate brain disease in patients with solitary metastasis, often with many, many years of benefit in those patients from the SRS alone. But in patients who have more than 1 site of brain disease, the likelihood of additional brain disease emerging is the impetus to think about double checkpoint blockade because of the durability of the benefit and the efficacy of that doublet therapy in patients with brain disease, especially when it is asymptomatic and when it does not require steroid therapy in anything over minimal dosages, which may mitigate some of the benefits of those doublet immunotherapies that we’ve talked about. For patients with asymptomatic brain disease, often picked up on screening tests that we do, we have a promising future with the ipilimumab/nivolumab combination, which will also have efficacy of course for extracranial disease in those same patients if they have this.
Matthew Fowler: You’ve touched on this combination a lot. To kind of wrap up this idea, I wanted to ask how do you decide if or even when to use single-agent immunotherapy versus a combination like nivolumab/ipilimumab?
John Kirkwood, MD, PhD: Yes, the single-agent therapy, meaning by that, anti–PD-1, either nivolumab or pembrolizumab, is highly effective and durably of benefit in a substantial fraction of patients with metastatic disease. Those who really do not want to accept the toxicity rate that was previously associated with ipilimumab/nivolumab are people who we often consider starting off with single-agent anti–PD-1 therapy. We have many trials of PD-1 plus other agents, and those trials are our first consideration for patients with untreated disease. One of those happily is the PD-1/LAG-3 combination that was reported at ASCO [the American Society of Clinical Oncology annual meeting] to be of benefit. It is perhaps of benefit to the same degree that we see with the first and second generation, now with the second- and third-generation agents. And with the lesser toxicity seen in RELATIVITY-047, and our own experience in the trial that we call here 18071, which is the lead trial of…in melanoma, we are able to offer patients benefits that we may have previously thought only attainable from the first and second generation with these second- and third-generation immunotherapies combined.
This transcript has been edited for clarity.