The Future Management of Melanoma

Transcript:Robert H.I. Andtbacka, MD, CM: I guess many of these unmet needs in the stage IV patient population also applies to the stage III patient population. And I think that additionally, there, it’s really the whole question of neoadjuvant therapy, as we talked about.

Michael A. Davies, MD, PhD: I think the other question there is—and this is applicable not only to stage III, but to earlier stages—can we do a better job of identifying which patients need aggressive intervention versus which patients are those who really won’t have the disease relapse? And then the question is, can we take what we’ve learned about the molecular biology and the immunology of this cancer to really personalize the management of earlier stages of disease as well?

Robert H.I. Andtbacka, MD, CM: So, really, what you’re saying with this, Mike, is moving away from a pure histological way of looking at this to more of a biological and biomarker perspective; trying to determine that even if you have a thin melanoma, you may have a much higher risk of recurring compared to other thin melanomas and identifying those patients up front through that.

Michael A. Davies, MD, PhD: Absolutely. Or a patient with stage III disease who actually is one of those patients who won’t relapse, and therefore shouldn’t go through the risk of the adjuvant ipilimumab, would be actually a powerful advance as well.

Antoni Ribas, MD, PhD: I think the biggest question we have in stage III disease is, do we use anti-PD-1 in the adjuvant setting? There have been clinical trials that haven’t been accrued. There’s a clinical trial from Bristol-Myers Squibb that was comparing ipilimumab at high doses with nivolumab. There’s an ongoing study in EORTC of pembrolizumab versus placebo, and then there’s the ongoing US Intergroup trial of S1404, which is actively enrolling patients comparing pembrolizumab with a control arm that’s either high-dose interferon or high-dose ipilimumab. That is a study that we would really like to see the results. If we’re able to impact with single-agent anti-PD-1 in stage III melanoma or we prevent melanomas going from stage III to stage IV, would that make a big benefit to this population and to the field?

Robert H.I. Andtbacka, MD, CM: Very good. Well, I want to thank you all. I think this has been very informative, learning about the current landscape of treatment of patients with advanced melanoma. So, before we finish though, I’d like to see if you have some final thoughts about this. Georgina, any final thoughts about where we are at the moment and where we’re going?

Georgina Long, MD: I think we’ve got a wonderful foundation. It’s been an absolute pleasure to be part of this knowledge and to have patients who respond in the last 5 years. It’s been fantastic, but we still have a lot of work to do. Primary and acquired resistance for all treatments is still an issue, poor prognostic factors in patients with high LDH is still an area we need to work on, and brain metastases are another issue. So, that’s what I’d say. It’s fantastic, enjoy what we’ve done, but we’ve got a lot more work to do. We need to enroll patients on clinical trials.

Robert H.I. Andtbacka, MD, CM: Mike?

Michael A. Postow, MD: So, I think we’ve also been in a melanoma space that’s really lucky that our treatments targeting the BRAF mutation, for example, and immune checkpoint blockade happened earlier in melanoma than they have in other disease. And so, we have an opportunity within melanoma to share our knowledge of immune therapies and targeted therapies really across the oncology spectrum. We’re grateful for our melanoma patients that first entered these clinical trials and all the investigators and physicians that have worked on this. And I think we have a duty now to really share that experience with many other diseases where we’re giving some of these checkpoint inhibitors and targeted therapies. That’s a huge opportunity. We should really think of our role more broadly and not just in melanoma; really helping patients, with many different types of cancers, with what we’ve learned in the melanoma space and what I hope we continue to learn.

Robert H.I. Andtbacka, MD, CM: Tony?

Antoni Ribas, MD, PhD: All this progress that we’re talking about hasn’t come by chance. It’s all been by applying knowledge to patients. It’s been by understanding the biology of melanoma, what drives melanoma to grow, how can we impact on it, how does the melanoma interact with the immune system, and how can we empower the immune system to attack the melanoma. We made progress. I think we’ll continue to make progress, but since this is a knowledge-based exercise, we then learn more about when it works, why it works, when it didn’t work, why it didn’t work, and what we should do next. And right now, we have several questions where we don’t know what the next step is, but all of this science that’s coming back from the patient to the laboratory will allow us to go back and develop the next generation of studies.

Robert H.I. Andtbacka, MD, CM: Mike?

Michael A. Davies, MD, PhD: I agree completely with all 3 of my colleagues. I think what we’ve illustrated in each of the cases we’ve discussed today is still that need to identify the ways to optimize the personalized therapy for each patient. So, how we actually use our existing therapies most appropriately still remains a challenge. It’s a challenge that’s much more pleasant now as we have better therapies. But, again, we still have a lot of clarity still to be achieved with identifying what is the right treatment for each patient.Robert H.I. Andtbacka, MD, CM: Very good. I want to thank all of you for participating. I also want to thank our viewers for viewing here, and I hope that this Peer Exchange® discussion has been useful for you and informative. I want to thank you all.

Transcript Edited for Clarity