Clinical Insights for the Future of Melanoma Care

EP: 1.A 47-Year-Old Woman with Metastatic Melanoma

EP: 2.First-line Therapy Options for Patients with BRAF-mutated Metastatic Melanoma

EP: 3.A Data-informed Approach to First-line Treatment Selection

EP: 4.Case-specific Recommendations for the Treatment of 47-Year-Old Woman with Metastatic Melanoma

EP: 5.Special Considerations for Patients with Metastatic Melanoma Presenting with Brain Metastases

EP: 6.Treatment Goals and Typical Response for Patients with Metastatic Melanoma

EP: 7.Managing Adverse Events in Patients Taking First-line Therapy for Metastatic Melanoma

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EP: 8.Clinical Insights for the Future of Melanoma Care

Hussein Tawbi, MD, PhD: We've made a lot of progress and metastatic melanoma, and again, we feel bold enough to speak of cures and being able to help our patients with long-term outcomes, but there remains a lot of unanswered questions and unmet need in these populations. Well, first is now that we have newer combinations that are less toxic like nivolumab and relatlimab, we still don't know the activity of that combination, for instance, in brain metastases, and whether we can help those patients with less toxicity. We also have limited data for patients that have rare subtypes of melanomas like mucosal, acral, uveal melanoma, anorectal melanoma. Those are subtypes for which we really have a lot of work to do. Finally, I would say toxicity management is really important. If we continue to evolve approaches to mitigate toxicity like not just early recognition, early intervention, but more mechanistically based interventions. We've been seeing some clinical trials of combinations with checkpoint inhibitors with say IL6 inhibitors and kind of other innovative approaches. If we can limit the toxicity, then we can really augment the benefit and we can treat more patients and treat them longer. That I think is also a really important unmet need. Not to end on my favorite topics but patients with brain metastasis remain a population that is not managed in the best possible way with the current therapies just because we don't have enough data. We have very clear data, ipilimumab and nivolumab. We know what targeted therapy is capable of doing, but we still need more data in terms of the newer combinations, how to sequence those combinations in patients with brain metastases, how to sequence them with radiation again or other local therapies like surgery for that matter. Then I would also add one last thing which we did not discuss that we still have a ton of work to do in the second line setting so we don't have any specific FDA approvals for the second line setting. We have some emerging data like ipilimumab and nivolumab in the second line or pembrolizumab, lenvatinib, or TIL therapy, which is really exciting but none of those are FDA approved in the second line. That is a huge gap in our portfolio.

In terms of what emerging therapies and clinical trials are really relevant, I would say again, the TIL therapy is probably the most exciting in the short term. That's approaches that could really help a lot of our patients. Despite the limited response rates of about 30% still, most of those are durable responses and patients that have already failed other therapies. That's a decent clinical outcome to look forward to. We have some trials that are coming up, as I said, with pembrolizumab and lenvatinib it will be interesting to see the results of those trials. Unfortunately, I say they're in the first line setting because again, it may complicate our decision-making in the first line, but that's a combination that's of interest. There are a lot of other agents that are coming along, novel checkpoint inhibitors, newer kind of variations to the theme on CTLA-4 inhibition, which I'm excited about. I think we have a lot to gain from CTLA-4 inhibition. There are a few molecules that are kind of trying to augment or reproduce the efficacy of anti-CTLA-4 with ipilimumab without as much of the toxicity. Those are kind of the things that I'm excited about.