Frontline Therapy in Melanoma

Source: OncLive, August 2019

Jeffrey S. Weber, MD, PhD: We talked about what you do when someone relapses after adjuvant therapy. What if someone presents to you de novo, Hussein, and they never had adjuvant therapy or had adjuvant therapy years ago? How do you decide—let’s say, in a BRAF-mutated patient—who gets BRAF/MEK? Who gets immunotherapy? Is it the single agent? Is it the dual agent? How do you make those decisions, and how do you present it to the patient?

Hussein A. Tawbi, MD, PhD: That’s a very good question. Just to back up a little bit, I do think the adjuvant therapies are defining new phenotypes of metastatic melanoma. All our currently approved therapies have been proven in the setting when there was no adjuvant therapy. All the clinical trials that have been conducted that led to approvals were phase III randomized trials, every single one of them in the first-line setting in previously untreated patients. This gave us really great data and gave us great agents in our hands and at our disposal now to treat our patients. Unfortunately, targeted versus immunotherapy has never been compared head-to-head in the first-line setting in melanoma to date. There are ongoing trials that have tried for several years to answer that question, but at this point we don’t have the answer to that.

In general, what we do know in the first-line setting for metastatic melanoma is that we have single-agent nivolumab and we have single-agent pembrolizumab, which have both substantial response rates and improvements in overall survival. We also have combination immunotherapy with ipilimumab and nivolumab that improves response rate, seems to improve PFS [progression-free survival], and has a modest impact on overall survival, but it also comes at the risk of doubling if not tripling the toxicity rate.

 

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