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Standard Adjuvant Therapy for Melanoma Within Reach

Angelica Welch
Published: Monday, Dec 11, 2017

We will also start seeing neoadjuvant studies looking at combinations of nivolumab plus ipilimumab or nivolumab alone. There are studies looking at treatment in the adjuvant setting versus the neoadjuvant setting to see what kind of outcomes happen. Perhaps there will be combinations of pembrolizumab and other agents, such as an IDO inhibitor or combinations of PD-L1 blockers plus BRAF inhibitors in patients who have BRAF mutations.

Are there any next steps with vemurafenib, even though the trial was technically negative?

I think not, because it is less effective than dabrafenib/trametinib and a little bit more toxic in the adjuvant setting. Also, the way the trial was designed was to look at cohort 2 first—which is made up of the stage IIIc patients—which did not show benefit. They weren't allowed to look at the other populations unless they saw benefit in cohort 2. Therefore, it was strictly interpreted as a negative trial.

If adjuvant nivolumab gets approved, how could it change the landscape?

If dabrafenib/trametinib and nivolumab both get FDA approval, then the majority of patients will get adjuvant nivolumab because it is something that can be used for the BRAF wild-type as well as the BRAF-mutant patients. It is something that community oncologists are likely to have more experience with than the BRAF or MEK inhibitors because they are using it for patients with different types of cancers—they are more confident managing the adverse events and are familiar with the benefit. When they are seeing patients, they are unlikely to have information of the patients’ BRAF status, so the easiest or default approach will be to order nivolumab for those patients. On the other hand, there may be patients who might be resistant to taking an intravenous treatment, or may not be eligible to receive a checkpoint inhibitor because they have an autoimmune condition or are on immunosuppressive drugs.

Is there anything regarding neoadjuvant therapy that you would like to touch on?

It looks like the combination of nivolumab and ipilimumab in the neoadjuvant setting is even more toxic than it is in the metastatic setting. Although in the 2 studies that have been done, everybody has been able to get to surgery, and it is hard to get more than 2 doses in the neoadjuvant setting with nivolumab plus ipilimumab. There are a lot of pathologic complete responses (pCRs) that have been reported, suggesting that nivolumab plus ipilimumab works fast. It remains to be seen if those pCRs in the neoadjuvant setting will translate into durable CRs. It is possible, and it may lay the groundwork for more novel regimens with lower doses of ipilimumab or other combinations with an anti–PD-1 agent that might also work quickly and enable patients to have surgery without postoperative therapy.

View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Advances in™ Melanoma: Exploring BRAF/MEK in Adjuvant and Neoadjuvant SettingsSep 28, 20191.5
Medical Crossfire®: What Does Data Tell Us About How to Optimize Checkpoint Inhibitor Strategies Across Lines of Care for Patients with Melanoma?Nov 30, 20191.5
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