Molecular Testing for Stage III Melanoma

Transcript:Jeffrey S. Weber, MD, PhD: OK. So the patient then goes to the surgeon. They also go to the medical oncologist. Hussein, what kind of testing do you do in a stage III patient who presents to you in clinic?

Hussein A. Tawbi, MD, PhD: Thank you, Jeff. I mean, what Vern started with is to say that now this requires multidisciplinary management. It always has been, but as we evolve our surgical approaches and actually do fewer surgical interventions that can leave our patients with lymphedema, we also get the chance to apply the recent results of adjuvant therapy trials that have proved benefit and are proven to be safe. As you guys know, we have now 3 adjuvant therapies that are actually FDA approved for the management of high-risk stage III melanoma patients. Those include 2 immunotherapy drugs. Both use the single agents—nivolumab and pembrolizumab.

And then we have, obviously, dabrafenib and trametinib as the combination targeted therapy that’s appropriate for patients who are BRAF mutant. So given that the BRAF-mutant population is appropriate for adjuvant therapy with targeted therapy, we feel strongly about actually understanding whether our patients have the BRAF mutation. We always include a period of time of waiting for the BRAF tests to come back, so we can tell if our patients are BRAF mutant or not so that they know which adjuvant therapy options could be available to them. In certain cases, patients prefer to use immunotherapy up front. In those cases, we may decide to start adjuvant treatment with immunotherapy before we hear about the results. But we make a very significant kind of push to make sure that our patients are aware of all the options available to them, and that does include BRAF testing in this space.

Jeffrey S. Weber, MD, PhD: Do you routinely test for PD-L1 [programmed death-ligand 1] or do other genomic testing that could impact on management?

Hussein A. Tawbi, MD, PhD: It’s really interesting to see that PD-L1 results, and more recently TMB [tumor mutational burden] and even in interferon gamma signatures, seem to be associated with differential outcomes in adjuvant therapy of melanoma. But none of them really rises to the point of being a predictive biomarker of response. We still kind of look at those tests more as interesting, as kind of additional data that, over time, may help us understand better where to apply adjuvant therapy. But at this particular moment in time, they are not used to determine which therapy to use in those patients.

Jeffrey S. Weber, MD, PhD: I was a little surprised to see that the gamma interferon signature, which I thought had the most value or utility, was really variably present in trials in melanoma and lung cancer. So I was actually a little surprised. But I agree. I think they’re not quite ready for prime time, other than BRAF testing.

Jason J. Luke, MD, FACP: I just wanted to make that comment, as someone who gets a lot of referrals that are coming from places that don’t have as much access to large medical centers, in the Midwest. Many community practices really haven’t integrated BRAF testing up front, and it often is the case that we get the patient and there was plenty of time to have done it, but it wasn’t necessarily done. Even thinking about the networks that you work with and your collaborating physician networks, it should be emphasized that this is now a team effort. It really comes from the surgeon, to the pathologist, all the way to the medical oncologist. Because otherwise we’re left in a position where we are not able to actually talk about all the available options. I would stress that as well. That information needs to be pushed. Other providers need to know it’s important to generate that information.

Vernon K. Sondak, MD: The surgeon and the pathologist, right at the beginning, can be critical members of the team by saying, “Hey, let’s do BRAF testing.” It can be done with immunohistochemistry [IHC] very quickly, even on a small tumor deposit in the sentinel lymph node. That’s what we try to do on essentially a reflex basis. And it’s important to educate the pathologist and the surgeons to know how this information is useful. It doesn’t mean you always use it. The BRAF mutation doesn’t guarantee this treatment. But having that information makes the subsequent discussion much easier.

Ryan J. Sullivan, MD: I think 1 last piece is that while BRAF IHC is a useful test, it doesn’t actually capture the V600K patients. It’s a screen for V600E. So if it’s not there, molecular testing should still be done, and it would be appropriate to do that.

Transcript Edited for Clarity