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 spoke with John Kirkwood, MD, PhD, director of the Melanoma Center at the University of Pittsburgh Medical Center Hillman Cancer Center, about using immunotherapy for treating melanoma and how to properly monitor responses in patients with metastatic melanoma.

In the video series, Kirkwood discussed the following:

Considerations for Immunotherapy Use When Treating Melanoma

Using ctDNA to Monitor Patients With Melanoma

Taking Drug Holidays Amidst Melanoma Therapy

To watch more videos from the CancerNetwork

 series, visit cancernetwork.com/oncview.

Don’t forget to subscribe to the “Oncology Peer Review On-The-Go” podcast on Apple Podcasts, Spotify, or anywhere podcasts are available.

Immunotherapy Response Monitoring in Melanoma

John Kirkwood, MD, PhD, discussed considerations for treating patients with melanoma using immunotherapy and how to properly monitor responses.

OncView™ Podcast: Immunotherapy Response Monitoring in Melanoma

 spoke with Emily Smith, MD, a dermatologist at the Ellis Fischel Cancer Center, University of Missouri, about a patient case published in the December issue of the journal 

Metastatic Basal Cell Carcinoma Arising From a Primary Cutaneous Carcinosarcoma

.” Smith and colleagues detailed a case regarding a 56-year-old man who the team of care providers diagnosed with metastatic basal cell carcinoma arising from a carcinosarcoma.

In the conversation, Smith spoke about what makes this patient's case unique, the timeline of this specific patient’s disease and treatment, and the rarity of basal cell carcinoma arising from a carcinosarcoma.

On this episode of the Oncology® Peer Review On-The-Go, Emily Smith, MD, discussed a patient case of basal cell carcinoma she and colleagues published in the journal ONCOLOGY®.

Oncology Peer Review On-The-Go: Patient Case of Metastatic Basal Cell Carcinoma Arising From a Carcinosarcoma

Today we are discussing adjuvant therapies in development for patients with melanoma with Ryan J. Sullivan, MD, a medical oncologist at the Massachusetts General Hospital, Boston, who specializes in the care of patients with advanced melanoma and leads clinical trials.

Just recently, there have been approvals of both an immune checkpoint inhibitor as well as BRAF-targeted oral agents for melanoma patients. What are the options for adjuvant therapy for patients diagnosed with melanoma?

Thank you for inviting and allowing me to discuss treatment options for patients with melanoma. You’re absolutely correct, there have been two approvals in the past year in the adjuvant setting for patients with stage III melanoma. The first is for nivolumab, an anti-PD-1 antibody which was approved based on data in the Checkmate 238 study which compared patients who received nivolumab vs patients who received ipilimumab.

All of the patients had Stage IIIB, IIIC, or stage IV melanoma that had been resected and were randomized on a one to one basis to receive ipilimumab, which was the control arm, or nivolumab, which was the experimental arm. The data showed dramatic improvement in relapse free-survival in patients who were treated with nivolumab.

In addition, patients who were treated with nivolumab had less severe toxicity than those who were treated with ipilimumab. On the basis of that data, nivolumab received approval from the FDA for patients with stage III melanoma that had been resected. The other approval was for the combination of two agents, dabrafenib, a BRAF inhibitor, and trametinib, a MEK inhibitor, and this combination had previously been approved for treatment of metastatic V600K or V600E mutant melanoma.

On the basis of the COMBI-AD trial, which was a study of these two drugs, dabrafenib plus trametinib vs a double placebo, the combination demonstrated significant improvement in relapse-free survival, distant metastasis-free survival and overall survival and was FDA approved in early 2018 for patients with stage III melanoma.

A few interesting points about adjuvant therapy for melanoma is that we have options. I think one option is nivolumab, another is dabrafenib plus trametinib and I think the prior options, either ipilimumab or adjuvant interferon or observation are less likely going to be implemented for patients. I think it is pretty safe to say that ipilimumab and interfernon for patients with stage III melanoma is no longer an appropriate therapy.

The other interesting thing to note about adjuvant therapy is that all of the trials that have been completed took place in an era where there was a different staging system. In 2018, the AJCC [American Joint Committee on Cancer] 8

 edition was implemented. There are a few changes in this staging system, probably for every cancer, but certainly for melanoma and in particular, in stage III melanoma there are now four sub-stages as opposed to three. Previously there were stages IIIA, B and C and now there are A, B, C and D.

Patients with stage IIIA in the older staging system had a higher risk of recurrence than in the new staging system which incorporates the thickness of the primary tumor amongst other features, including nodal involvement, which helps us to concentrate most of the risk to patients with stage IIIC or stage IIID melanoma.

It's a bit difficult to know how to take the data from these trials and apply it to those patients who have the lower risk Stage III disease, because the indication for nivolumab and trametinib and dabrafenib are in patients with stage III resected melanoma but that may not be appropriate for all stage III melanoma patients.

I think it’s important to recognize that there is a new staging system and because of that, we need to take that staging system into context when we are making recommendations for adjuvant therapy.

The other thing that changed was the surgical management of these patients. Patients who have a sentinel lymph node biopsy, if they have a high enough risk primary melanoma, if there is pathological involvement of the sentinel lymph node, they should have a complete lymph node dissection which is essential the removal of all of the lymph nodes in that lymph node basin.

There was a second MSLT study, MSLT-II, which compared patients who received a sentinel lymph node biopsy and randomized patients who had a positive sentinel lymph node biopsy to either lymph node basin monitoring with ultrasound or completion node dissection and the data, which was published in June 2017. This demonstrated that patients who had completion of node dissection didn’t appear to have any better overall survival or distant metastasis-free survival than those patients who did not have a complete lymph node dissection.

How that impacts our understanding of the data from the COMBI-AD and the Checkmate 238 is that those trials were conducted in patients with Stage III melanoma who had complete lymph node dissection. So, again, this is a slightly different population than those we are seeing right now. With that said, it is clear that myself and my colleagues are offering patients with stage III melanoma either nivolumab or dabrafenib and trametinib as a result of the findings of the two trials I mentioned.

Switching to trials in progress, there are now immunotherapy combination approaches that are being tested in the adjuvant setting. Can you talk about the larger and/or more interesting trials that are ongoing and their rationales?

There are a number of combined checkpoint inhibitor regimens that are being tested. They have shown particularly with respect to ipilimumab and nivolumab, better response rates, possibly better progression free survival and at least numeric advantages in overall survival.

That is not statistically significant nor is it statistically sound to compare the treatment arms of Checkmate 067 which compared ipilimumab and nivolumab vs nivolumab vs ipilimumab. There is a trial in stage III ipilimumab and nivolumab called Checkmate 915 that has completed accrual and compared patients, and was initially supposed to compare patients in one of three arms, very similar in design as the Checkmate 067 trial except that was for metastatic melanoma and this trial is for stage III and stage IV resected melanoma.

The Checkmate 915 trial is comparing patients who are receiving ipilimumab and nivolumab vs ipilimumab or nivolumab in the adjuvant setting. With the results of the Checkmate 238, when the trial was launched, the Checkmate 238 data had not yet been reported but it was soon after so the ipilimumab was removed from the design so it became a two arm study of ipilimumab and nivolumab vs nivolumab.

Now, in the metastatic setting, the data from the combination of immune checkpoint inhibitors is interesting. You can do a lot with dosing and it seems like when you give two drugs, an anti-CTLA4 antibody like ipilimumab and an anti-PD1 antibody like nivolumab together, there is much higher toxicity than when you give either by themselves. However, there are modifications that can be made to the dosing and because the toxicity seems to be dose-dependent on ipilimumab, you can give a lower dose of ipilimumab with a normal dose of nivolumab and you can give less frequent dosing of ipilimumab. 

The Checkmate 915 study is actually looking at a lower dose of ipilimumab with a normal dose of nivolumab and is being given every 6 weeks as opposed to every 3 weeks, which is the standard use of the FDA-approved dose for metastatic melanoma. The standard is higher dose ipilimumab with lower dose nivolumab every 3 weeks for 4 doses and then you switch to nivolumab and stop giving ipilimumab.

In this 915 trial, ipilimumab was continued every 6 weeks at the lower dose and the nivolumab was given every 2 weeks. Because there seems to be activity with the combination in stage IV melanoma, the idea was could we maybe take advantage of that activity in stage III disease and so that is the regimen. We look forward to results of that study in the next couple of years.

What about targeted therapies or trials that are combining different modalities? Are there any in the adjuvant setting that you could highlight?

There are three FDA-approved BRAF-MEK inhibitor combinations and technically, any of those could be used in the adjuvant setting as part of a clinical trial because only the combination of dabrafenib plus trametinib has been approved for adjuvant use. The other issue clinicians are interested in is whether or not there will be any benefit to combining targeted therapy with immunotherapy and there is talk of launching a cooperative group trial of combined immune checkpoint inhibitor therapy plus targeted therapy vs BRAF targeted therapy vs anti-PD1 immunotherapy.

That would be a fairly definitive look at whether or not the addition of immunotherapy plus targeted therapy will end up being a more effective therapy than giving either of the two components alone. There is some rationale for combing targeted with immunotherapy. There is a lot of preclinical data as well as  analysis of tumor samples that suggest that BRAF inhibitors in part work by activating the immune system and that the way that they activate the immune microenvironment is one that would predict benefit from anti-PD1 therapy.

There are a number of phase I and recently phase III trials demonstrating some efficacy of triplet combinations. In the case of the randomized study, it was dabrafenib plus trametinib vs dabrafenib plus trametinib with pembrolizumab. That study showed that the triplet therapy improved progression free survival compared to the doublet dabrafenib plus trametinib therapy and possibly improved duration of response in patients who got the triple therapy. I think there is clear rationale for looking at combining modalities but it’s not clear whether or not that will translate into better overall survival. The data from that randomized study that was presented at ESMO [European Society For Medical Oncology] this year did not have enough follow-up to demonstrate an overall survival advantage and ultimately, that is what we are looking for.

In general, how do you approach choosing an appropriate adjuvant therapy for a patient?

This is the right question to ask and it is nuanced. Most of us try to simplify it as much as we can. Some of my colleagues flat out believe that immunotherapy is better than targeted therapy based more on philosophical grounds than necessarily strong data to support that. They will offer anyone, whether they have a BRAF mutation or not, single agent anti-PD therapy outside of potential enrollment on a clinical trial as their standard adjuvant therapy for patients with resected stage III or resected stage IV melanoma. Some of my colleagues, if the patient’s melanoma has a BRAF mutation, will offer BRAF targeted therapy for those patients and if there is not a BRAF mutation present, will recommend single agent anti-PD1 therapy and use the BRAF typing to stratify treatment decision.

I don’t think either of those approaches are right or wrong. What many of my colleagues do is to have long conversations, and these used to be short conversation with patients but these have gotten longer as there have been more treatment options available, and so we discuss the pros and cons of each of the therapies. In the absence of head-to-head comparisons therapy for BRAF-mutated patients who have stage III melanoma, as far as we know, it’s just as good to give a BRAF-MEK inhibitor combination therapy as it is to give single agent nivolumab, so a lot of it comes down to the toxicity profile.

Patients are less likely to have severe toxicity with nivolumab, however, you are much more likely to have permanent toxicity with nivolumab and so a lot of our patients will chose the therapy that may have less permanent toxicity or the therapy that has less severe toxicity in general. It is definitely one of the scenarios where we need to get the input from the patient to help make the right recommendation. My general philosophy is that if a patient is BRAF-mutated and have high-risk melanoma that has been removed, the likelihood is that they will need both targeted therapy and immunotherapy over the course of their lifetime to treat their cancer.

I often think about offering BRAF-targeted therapy in the adjuvant setting because it appears to work a little bit differently in the adjuvant setting than it does in the metastatic setting. For example, the data we have from COMBI-AD suggests that patients can stop therapy after 1 year of treatment and have sustained improvement in relapse-free survival and overall survival compared to those who got placebo. In the metastatic setting, it is very rare for someone to stop BRAF-targeted therapy and have ongoing control of their disease, most patients will relapse even if they have been on therapy for 5 years and had a complete response. They will stop and the disease will grow back.

In the adjuvant setting that does not seem to be the case, there seems to be a separation between the patients who receive the combination vs those who received placebo, suggesting that at least some percentage of patients are cured with dabrafenib and trametinib in the adjuvant setting vs, I think, there are very few patients cured with the BRAF-MEK combinations in the metastatic setting.

So because the combination is potentially curative in the adjuvant setting and likely not curative in the metastatic setting, it seems to be working differently. Nivolumab and ipilimumab, have definite improvement in relapse-free survival and ipiliumab has improvement in overall survival and we expect that nivolumab will have improvements in overall survival compared to patients receiving ipilimumab in the Checkmate 238 study.

We think it is curative for some stage III patients and we think it is likely curative for some patients with stage IV disease. It is not clear whether the percentage of patients cured in the adjuvant setting is different from the percentage of patients cured in the metastatic setting, and so nivolumab may be operating very similarly in the adjuvant setting. So, when you have the opportunity to offer one of two treatment regimens, thinking that you will probably have to give both of those types of therapies over the course of their treatment, giving them something that works differently in the adjuvant setting compared to the metastatic setting is at least, to me, and some of my colleagues, seems to make a lot more sense than giving a drug that likely works very similarly in the adjuvant and metastatic settings.

That is the rationale I often use to justify the use of dabrafenib plus trametinib in patients with stage III melanoma who are BRAF-mutated, over nivolumab, in the absence of any further data that supports that nivolumab therapy is better than dabrafenib plus trametinib. Obviously, in patients who are BRAF wildtype, the decision is much simpler, nivolumab is better than ipilimumab, and pembrolizumab, like nivolumab, is probably going to be shown to be better than ipilimumab or interferon in a cooperative group study that closed enrollment a few years back.

I am pretty confident that anti-PD1 therapy is the right therapy for BRAF wildtype patients at high-risk of recurrence after curative intent surgery and I think it is pretty straightforward to recommend an anti-PD1 therapy for that patient.

Cancer Network speaks with Dr. Ryan J. Sullivan about adjuvant therapies in development for melanoma patients.

Dissecting Adjuvant Therapy Options in Melanoma

As part of our coverage of the 2018 Annual Meeting of the American Society of Clinical Oncology (ASCO), held in Chicago, June 1–5, we spoke with Jennifer Wargo, MD, about strategies to combine immunotherapy and targeted therapies for the treatment of cancer. Dr. Wargo is a surgical oncologist who specializes in melanoma in the departments of Genomic Medicine and Surgical Oncology at the MD Anderson Cancer Center at the University of Texas in Austin, and runs a translational lab that studies the body’s immune response to tumors. She discussed this topic at an ASCO Educational Session, entitled “Rational Combinations With an Immuno-Oncology Backbone.”

There are already a few immunotherapy-immunotherapy combinations approved for melanoma, and also two targeted therapy combinations. What have we learned so far about the development of these types of combinations that could help us develop additional combination regimens for melanoma and other tumor types?

I think what we’ve learned is that even though monotherapy regimens using immunotherapy or a targeted therapy can work for some patients, it’s really only in a minority of patients that this works well. The majority of patients will need a combination therapy approach.

Now, certainly, we have seen different combination regimens, [such as] immunotherapy-immunotherapy regimens such as ipilimumab plus nivolumab approved for melanoma-and potentially this combination will be approved for other cancers. The issue with these regimens is that we see significant toxicity, so I think there is still room for progression. Can we test immunotherapy-immunotherapy combinations that are potentially just as efficacious but less toxic? I think there are some being tested now, [and the results of these studies] may help answer that question.

In addition, can we actually use targeted therapy in combination with immunotherapy to improve responses? The rationale for this goes back several years. Specifically for melanoma, targeted therapy was really first approved and shown to be very effective in treating patients with stage IV melanoma. But we learned early on that patients do progress on therapy, and that the duration of response is relatively short-lived. Now, in the early days of immunotherapy for melanoma, we know that with treatment with the initial immune checkpoint inhibitor that was approved, an anti–CTLA-4 [cytotoxic T-lymphocyte–associated antigen 4] antibody, we saw that a minority of patients actually responded but the patients that did respond had durable responses.

Early on, there was clinical interest in combining targeted and immunotherapy agents, hoping that we would get to a higher response that we see with targeted therapy and the prolonged response seen with immunotherapy. Now, with the advent of anti-PD1 [programmed death 1] and anti-PDL1 [programmed death ligand 1] immunotherapy for melanoma, we are certainly seeing higher response rates, but the majority of patients still do not respond, or the responses are not durable. So, there is always room for these different mechanisms of action combinations.

On top of all of this, we also know that there is a strong scientific rationale for combining targeted therapy with immunotherapy. Namely, we know that these oncogenic mutations can actually cause immune evasion in tumors and that by blocking these oncogenic mutations, you can make these tumors more immunogenic. We showed this in melanoma several years ago. Now there are ongoing studies in patients, combining targeted therapies with immunotherapy, namely with immune checkpoint antibodies-and this approach is showing great progress.

Are there specific immunotherapy-targeted therapy combinations being tested, and what are we beginning to understand about combining these types of therapies?

Definitely. Some of the first targeted therapy- immunotherapy combinations involved BRAF-targeted oral therapy in combination with cytokine immunotherapy such as interleukin-2. I can tell you that this combination wasn’t very effective for a number of reasons.

One reason is that [the interleukin-2] trial was started in the setting of all of these checkpoint inhibitor antibodies that were being tested, so as soon as the trial started, these newer agents were just starting to be tested in clinical trials. [As a result], the interleukin-2 trial just was not getting a lot of traction.

In addition, we know that interleukin-2 itself can actually increase the frequency of regulatory T cells, which actually inhibit the immune response you want against the tumor. We saw evidence of this in a trial that we ran out of the Massachusetts General Hospital in which there was some hint of efficacy, but we also saw that there were more regulatory T cells in the patient’s tumor microenvironment after patients were treated with interleukin-2. Now, that is some of the early work, and some of this work included combining anti-CTLA4 antibodies with BRAF-targeted agents.

The early trials combining these two agents were somewhat disturbing in that there was significant hepatotoxicity. Because of this, these trials were stopped early on, but now with the use of other immune checkpoint inhibitors in combination with targeted agents, we are seeing less toxicity and higher efficacy. Some of these agents that are being tested in clinical trials are dabrafenib (an oral BRAF inhibitor) and trametinib (an oral MEK inhibitor), combined with PDR1, which is an antibody that targets the PD-1 checkpoint molecule.

Many other trials are also underway, so this is not only being tested in melanoma but in other solid tumors, as well as in hematologic malignancies. There are hints of efficacy but it will take some time to get the full readout; [this is] because we know that when using targeted agents, there can be a very high response rate, but what we are looking for in these trials is durability of response rates.

In general, to figure out what immunotherapy-immunotherapy combinations make sense to test, are these first being tested in the lab to [better understand] how the immune system responds before taking these into the clinic?

For the immunotherapy-immunotherapy combinations, we still have a good deal to learn. I think there are some very strong lessons that we can learn from preclinical models. However, preclinical models are not always perfect, and we don’t necessarily see the same toxicity in preclinical models compared to what we see in patients, so we need to think outside the box regarding how best to test these different combinations.

One particularly appealing strategy is using these agents in a neo-adjuvant setting before a tumor is actually resected. So if a patient comes in with a potentially resectable metastases, we are running some novel clinical trials looking at immunotherapy-immunotherapy combinations to test, not only [to determine] how effective these are, but [to learn] what are their effects on the tumor microenvironment. [Using this approach], we can better understand if they are working, why are they working, and if they are not, what we can do to make these therapies work better in this setting.

From a research perspective, are there additional questions that you and other researchers are addressing that will help us to come up with better immunotherapy-targeted therapy combination strategies?

I think what we are grappling with now is that there are just so many combination trials that are being run and a lot of these are not [pharmaceutical company–sponsored trials], but investigator-initiated trials.

In 2017, there were close to 500 new trials that combined a checkpoint blockade molecule, and they were testing these drugs in combination with all kinds of different strategies. One of the biggest issues here is that, as it stands, these approaches have been somewhat fragmented and disorganized. The approach is researchers doing lots of small trials and not necessarily with consistent collection of biospecimens or even looking at the same clinical endpoints. The thing that we need to do as an oncology community now is to come together to design studies that actually test these combinations as a more global strategy and in a coordinated and more concerted fashion.

I think the neoadjuvant studies provide a real opportunity, and we are working with others globally to form a neoadjvuant consortium for melanoma. The goal would be to work with other investigators to extend that beyond melanoma to other cancer types. Efforts like this, as well as efforts through the Friends of Cancer Research…can really make a big difference.

American Society of Clinical Oncology Annual Meeting (ASCO)

Patients who responded to anti–PD-1 therapy and experienced prolonged progression-free survival had a much greater diversity of gut bacteria.

Determining the Role of the Gut Microbiome in Melanoma Treated With Anti–PD-1 ICIs

As part of of our coverage of the 2018 American Society of Clinical Oncology (ASCO) meeting, being held June 1–5 in Chicago, we spoke with Ryan J. Sullivan, MD, about several melanoma presentations of interest at the meeting, as well as questions of major clinical importance in the management of melanoma today. Dr. Sullivan is a medical oncologist at Massachusetts General Hospital, Boston, Mass., who specializes in the care of patients with advanced melanoma. He is also leading clinical trials investigating the development of predictive biomarkers in the treatment of patients with melanoma.

Are there one or two key presentations of clinical trial data at the meeting that you feel could potentially be practice-changing?

This is another year when the practice-changing trial results are not part of the oral abstract and poster sessions, and may or may not find their way into the poster sessions. The main issue with melanoma right now is sorting out the best way to treat patients upfront, and there are ongoing trials addressing that. Some abstracts at the ASCO meeting are presenting economic analyses of sequencing therapies and comparing different treatment approaches head-to-head.

The trials that will truly be practice-changing are the ones looking at how to treat patients after upfront immune checkpoint inhibitor therapy, because well over 50% of our patients are progressing on those treatments and we need to have better therapies for these patients. Some of these trials are early-stage, some in melanoma but some are single-agent [studies] or combinations of novel immune-targeting agents plus, usually, an anti-PD1 antibody. And ultimately, some of those strategies will be moved forward if the preliminary data hold up.

So there are a number of abstracts, some in the melanoma program and some probably in the developmental therapeutics immunology program, that give us a better sense of what types of therapies are being studied and [will provide] the preliminary evidence to understand whether we should move those approaches forward into larger trials.

Are there other, specific presentations at the meeting that you would like to highlight? 

There are some melanoma trials with additional follow-up data. One is [overall survival data from] COLUMBUS, which is a phase III trial of encorafenib (an oral BRAF inhibitor) plus binimetinib (an oral MEK inhibitor) vs vemurafenib or encorafenib in patients with 

phase II [data on] epacadostat (an IDO inhibitor) plus nivolumab trial data

 will be interesting to see, although in the context of the epacadostat-plus-pembrolizumab phase III trial that failed to show an improvement in metastatic melanoma patients compared to pembrolizumab alone, I am not sure how exciting the data will be. [I'm also in interested in] the 

phase III data on pembrolizumab plus epacadostat

The 4-year survival data on patients who were on pembrolizumab for 2 years and then went off treatment [will be useful]. I always like seeing these types of data-on the patients who stopped treatment after 2 years and continued to be followed-in order to see how long these patients can go before needing new therapy and [experiencing] progression. These data are absolutely practice-affirming, because we are stopping patients who are on an anti-PD1 [programmed death 1] therapy and are having great responses. And any additional data help support us in speaking to patients and saying “here are the data, and we feel more comfortable than ever because we have these additional data.” Every year that [this type of outcome] is presented, I am thrilled, because [such findings provide] more and more confidence that it is ok to stop these therapies in patients after a while.

 on adjuvant dabrafenib plus trametinib, a BRAF-inibitor plus MEK-inhibitor combination based on the AJCC 8 [American Joint Committee on Cancer 8th edition Cancer Staging Manual] classification will [likely provide some useful information]. This will not change the dataset, but at least we will be able to apply the data that are presented in the contemporary AJCC staging system-whereas the trial itself was run under the prior staging system, which is important but not particularly exciting. It will help in the day-to-day management of patients, to translate those data into this current era. In addition, [there are] updated data from the 

Checkmate 238 adjuvant trial of nivolumab vs ipilimumab

. And it’s always great to window shop at the poster session, to see what researchers are working on that I didn't know about. That is certainly something I am looking forward to.

Are there any trials you are a part of that will be presented at the meeting and which you could highlight? 

entinostat (an HDAC [histone deacetylase] inhibitor) and pembrolizumab

 that is part of the poster session, which is a dose-expansion study in melanoma as part of a phase Ib trial. There's also a trial, in the developmental therapeutics section, of an 

oral PI3-gamma inhibitor, IPI-549, plus nivolumab

 (as part of a poster discussion session). There will not be any melanoma patient data [from the study] presented at this meeting, but this is an example of an emerging combination that could be potentially useful in [treatment of] melanoma and other tumor types.

Lastly, what is your perspective on how the treatment paradigm for patients with metastatic melanoma has changed in the last 10 years? It seems that there has been quite a bit of progress, but there are still unmet needs that have to be addressed. 

It can’t be overstated that there has been a dramatic change in the way patients with metastatic melanoma are treated in the last 10 years. There are almost a dozen drugs approved or about to be approved [for treatment of melanoma], including combination therapies. We essentially went from not having anything for our patients to having many options, and this has translated to an increase in survival.

There was a study of melanoma patients enrolled in clinical trials [that was] published in 2008 and covered the span from 1975 to 2005. And the 1-year survival to begin with was about 25%, and it hadn’t changed much in the 3 prior decades. Then, when you look at the clinical trial data from some of the really large, randomized phase III trials such as COLUMBUS, Checkmate 067, and Keynote 006, the 2-year survival is at or above 50%, up from a 1-year survival of 25%; and the 3-year survival is somewhere between 40% and 50%.

We don’t know what the 5-year survival will be for some of these trials, but contrast the 5-year survival from that meta-analysis, where the survival at 5 years was 5% or less. And [in the future] we are probably going to be [achieving survival rates] 7 or 8 times that at 5 years, which is amazing. This really highlights [not only] that a lot of drugs were approved but also that these drugs had [a significant impact] on patients’ lives. The obvious first unmet need is that the majority of metastatic melanoma patients are going to die from their disease, and so the 5-year survival rate of 30% or 40% is not good enough, even though it is so much better than before we had these drugs.

Medical oncologist Ryan J. Sullivan shared some interesting melanoma-related presentations from the  2018 ASCO Annual Meeting.

Skin Cancer & Melanoma

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