Michael B. Atkins, MD: In patients whose tumors don’t have a BRAF mutation, we tend to use immune therapy as our first treatment approach, and currently, those are with checkpoint inhibitors and anti–PD-1-based therapies, either nivolumab or pembrolizumab. We believe that the data show that combination anti–PD-1/anti-CTLA4 immunotherapy is more effective both in producing tumor responses and long-term tail-of-the-curve survival than single agents. So, that’s our go-to treatment of choice, and we essentially give combination therapy to everyone who we perceive would be able to tolerate combination treatment.
The only patients who we would typically give anti–PD-1 monotherapy to are patients who are elderly and who have significant comorbidities that might make it hard for them to tolerate the side effects, those who have autoimmune conditions that are preexisting that might be overactivated if we gave them combination therapy, and also patients who might have had ipilimumab before in the adjuvant setting.
Michael A. Postow, MD: We’ve been hearing about some initial treatment options for patients with BRAF wild-type melanoma, and that really includes various different immune therapy approaches that block the PD-1 protein, such as with drugs like pembrolizumab or nivolumab and occasionally the combination of ipilimumab and nivolumab. But unfortunately, despite our best efforts at giving these patients without a BRAF mutation immune therapy as an initial treatment approach, many of these patients will still need some second treatment after their first initial immune therapy attempt. And so, what kind of treatments could we consider for second-line or beyond in our patients with BRAF wild-type melanoma?
So, if we think about PD-1 as an important drug in the first-line setting, either alone or in combination with ipilimumab, the second-line question really rests on whether or not the patient has had ipilimumab in combination with PD-1 in the first-line setting. If I have a patient that has had PD-1 alone in the first-line setting and they don’t have a BRAF mutation, then I’m thinking about giving this patient ipilimumab in the second-line setting, either alone or possibly in combination with nivolumab.
Now, we don’t officially have data for ipilimumab in combination with nivolumab in the second-line setting after PD-1 progression. However, it is interesting to think about whether the combination of ipilimumab and nivolumab as a second-line treatment after PD-1 progression is better or worse than just doing ipilimumab monotherapy. But I think the key for second-line treatment for BRAF wild-type patients is that ipilimumab would be a really good second-line treatment, either alone or in combination, if the patients haven’t had the combination just quite yet. But in the second-line setting, we’re also thinking about clinical trials. We’re also thinking about potentially if a BRAF wild-type patient has other mutations that could be targeted. And we have to always consider whether chemotherapy is still important to the patient, but I would think about that after other clinical trials on ipilimumab.