Malignant Melanoma: Contemporary Management - Episode 16

Future of Treating Melanoma


Jeffrey S. Weber, MD, PhD: This has been extremely informative. But before we end this discussion, I’d like to get some final thoughts from each of the panelists. Dr Jason Luke?

Jason J. Luke, MD, FACP: I think this year’s ASCO [American Society of Clinical Oncology Annual Meeting] really identifies how we have made a tremendous amount of progress yet have a long way to go. We need to be judicious in thinking through that as our prior conversations outline. It just really needs to be highlighted that clinical trial participation is still essential. Because while we made significant progress, it’s not clear yet what the next step is. And without continuing to push the field forward, we’re not going to make that progress. Especially patients who are in the refractory disease setting. They need to be referred for clinical trials because we really just don’t know what to do with them yet.

Jeffrey S. Weber, MD, PhD: Are you worried that we have more trials than patients?

Jason J. Luke, MD, FACP: I worry that our effective options are very advantageous, perhaps in the standard-of-care setting. And it becomes very easy not to really take into account that a patient could participate in a trial. And if we wait too long, then we remember what melanoma was like before we had any kind of effective therapy.

Jeffrey S. Weber, MD, PhD: Dr Vern Sondak?

Vernon K. Sondak, MD: Great points. A couple of key take-home messages. 1) We may be using surgery less, but we have to be very closely following our patients, so that when they need surgery, they get surgery. We want to consider neoadjuvant treatment for patients with palpable nodes, especially bulky nodes. And we have so many agents and choices now that the sequence—what do we do first, which ones do we do—are extremely important choices. But in the end, most patients, if they’re BRAF mutant, are going to get immunotherapy and targeted therapy at some point in their career. Sequence is everything right now.

Jeffrey S. Weber, MD, PhD: Dr Ryan Sullivan, your thoughts?

Ryan J. Sullivan, MD: I think if we had no other effective agents in the next 10 years, we’d be very busy trying to figure out what to do for our patients. We could probably improve the survival of our patients if we just knew which patients we should offer which therapies to. I think it’s a push for continued efforts in translational research to truly understand which patients we should sequence, starting with which therapies, which patients we should give everything to, and which patients in the, say, adjuvant setting we should treat or observe. And I think as we move forward, we’re not going to be able to slow down, nor do we want to, the tsunami of clinical trials in this space. And I think we definitely need to put more of our patients on the clinical trials, particularly in a scenario we don’t know what to do, like the second-line setting after ipilimumab or after a PD-1 [programmed cell death protein 1] inhibitor or ipilimumab-nivolumab. But I think we also need to really pay attention to trying to figure out which is the optimal way to select treatments for our patients.

Jeffrey S. Weber, MD, PhD: I think you’re arguing for biomarkers for selection, and I absolutely think that is the case. Interestingly, at this ASCO, there’s probably more interesting biomarker stuff happening than actually new therapies. Lastly, Dr Hussein Tawbi, your thoughts.

Hussein A. Tawbi, MD, PhD: I would echo most of my colleagues, and I would agree. I think the greatest progress we’ve had in the last few years has been in the adjuvant space, where we really can improve the outcomes of those patients and decrease their risk of relapse and hopefully cure more patients. But there’s an urgent need to figure out which ones we should not treat. And predictors of response, predictors of toxicity, are going to be really important. And that’s where the biomarkers will be important, and also possibly bring combinations into this space for those patients [who] will need them. And I think the neoadjuvant setting will be a great setting for us to try to make some sense of mechanisms of action of some of the drugs but also how to improve the outcome of the highest-risk patients in the localized disease.

In the metastatic setting, I think we’re at a point in time in which we have new, interesting combinations like triplet therapies that are coming. We’re throwing the kitchen sink that we now have at those patients, and it will really be interesting to seeing whether that will improve the outcome of those patients. But we’re clearly defining new populations. We’ve defined the patients that are asymptomatic with brain metastases, that are asymptomatic off steroids, and now we have a great treatment for them in the form of combination ipilimumab and nivolumab. But there’s still 40% who progress, and at this ASCO we have identified a population who we’re not doing that well for with brain metastases, because of steroids. We really need to think for those patients what to do.

And then in the second-line setting, as you’ve heard from most of my colleagues, we are at a time in which we don’t know what the next step forward should be. And I think being able to go deep on the science and really understand each of those drugs that we’re bringing along—what do they give us in terms of a pharmacodynamic impact in the tumor—Is going to be critical in telling us which ones should graduate to be the next therapy tested in a phase III trial and potentially the next standard of care.

Jeffrey S. Weber, MD, PhD: Great. Well, thank you all for your contributions to this discussion. On behalf of our panel, we thank you for joining us, and we hope you found this discussion to be useful and informative.

Transcript Edited for Clarity