ASCO20 Virtual Scientific Program Research Round Up: Head and Neck Cancer and Melanoma

August 13, 2020
Download MP3 (18.09 MB/26:29)

In the annual Research Round Up podcast series, Cancer.Net Associate Editors answer the question, “What was the most exciting or practice-changing research in your field presented at the ASCO20 Virtual Scientific Program?” In this episode, editors discuss new research in the fields of head and neck cancer and melanoma.



ASCO: You’re listening to a podcast from Cancer.Net. This cancer information website is produced by the American Society of Clinical Oncology, known as ASCO, the world’s leading professional organization for doctors who care for people with cancer.

The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Cancer research discussed in this podcast is ongoing, so the data described here may change as research progresses.

Every year, the ASCO Annual Meeting brings together attendees from around the globe to learn about the latest research in the treatment and care of people with cancer. This year, attendees from 138 countries worldwide gathered virtually for the ASCO20 Virtual Scientific Program, held Friday, May 29 through Sunday, May 31.

In the annual Research Round Up podcast series, Cancer.Net Associate Editors answer the question, “What was the most exciting or practice-changing research in your field presented at the ASCO20 Virtual Scientific Program?” In this episode, editors discuss new research in the fields of head and neck cancer and melanoma.

First, Dr. Ezra Cohen will discuss new research in squamous cell carcinoma of the head and neck and adenoid cystic carcinoma. Dr. Cohen is Co-Director of the San Diego Center for Precision Immunotherapy, Associate Director of Translational Science and leads the Solid Tumor Therapeutics research program at Moores Cancer Center at UC San Diego Health. He is also the Cancer.Net Associate Editor for Head and Neck Cancers.

View Dr. Cohen’s disclosures at Cancer.Net.

Dr. Cohen: Hi. This is Dr. Ezra Cohen from University of California, San Diego, Moores Cancer Center. And today I'll be reviewing head/neck cancer abstracts from the American Society of Clinical Oncology Annual Meeting. I have consulted for Merck in the past.

As all of us know, this meeting was virtual this year, but we had an opportunity to see the broadcasts through the virtual website. And there were a few abstracts that I thought were relevant to not only current standards of care but also to the future of research in head/neck cancer. The first one I'll talk about is a Japanese study that compared post-operative chemo radiotherapy of 3 weekly cisplatin versus weekly cisplatin in high-risk patients with squamous cell carcinoma of the head and neck. This was indeed an adjuvant trial or a post-operative trial, and really addressed an important question in the field that had been controversial and perhaps continues to be going forward.

The investigators compared a dose of 40 milligrams per meter squared given every week versus the standard 100 milligram per meter squared of cisplatin given every three weeks and assess patients for local-regional control and overall survival. Interestingly enough and as opposed to some prior reports, the combination of weekly cisplatin and radiation actually proved to be superior with respect to both local-regional control and survival while providing a regimen that was fairly well-tolerated and in the aggregate actually had a lower toxicity rate than the every 3 week cisplatin, suggesting that at least at 40 mg per meter squared, we may have a regimen that is in the post-operative setting more efficacious, and better tolerated, and that it may be time to revisit standards of care or at least to perhaps accept 2 different standards of care in the post-operative setting; one being high dose every 3 weeks cisplatin and the other being weekly cisplatin.

The other relevant abstract from the oral session was another randomized trial, this time from South Korea. Looking at adenoid cystic carcinoma, here patients were randomized to either receive a vascular endothelial growth factor receptor inhibitor named axitinib vs. placebo in patients with metastatic disease. This class of agents that axitinib belongs to has been noted to be active in adenoid cystic carcinoma for some time, but there had never really been any randomized trials comparing axitinib to any treatment and certainly not to observation or placebo. Fifty-seven (57) patients were enrolled and progression-free survival was the primary endpoint, in fact, 6-month progression-free survival. And what the investigators found was that this was much better in the axitinib patients versus placebo. In fact, about 70% of patients in the axitinib arm failed to progress and were still alive versus only 23% in the placebo arm. Now, this was not a large enough trial to change registration or the label of the drug, but it certainly, for patients with adenoid cystic carcinoma who have very few treatment options, does provide a therapy that now is at the very least validated through a randomized phase II trial and gives us a little bit more confidence in using this entire class of agents in patients with adenoid cystic carcinoma.

One of the other targeted therapy studies that I think is also worth highlighting from the meeting was that using tipifarnib in patients with HRAS mutations. This was a study conducted across several different cancer types, but the most commonly enrolled patients and, in fact, a specific cohort were for patients with head/neck squamous cell carcinoma. And interestingly enough, the investigators having enrolled 18 patients found an overall response rate of 56%, arguably much better than we would be able to do with chemotherapy in these patients or any other targeted agent for that matter. And again, not a study that would change the label or standards of care but certainly worthwhile watching the efficacy of this agent tipifarnib going forward in patients with HRAS mutations.

And then from the poster discussion session, I think we saw some interesting data that may be a prelude to the future, especially with immunotherapy. Christine Chung presented the experience of cetuximab and nivolumab, an EGFR and a PD-1 antibody in combination, and found that to be quite active, again, in a non-randomized manner but certainly enough activity to think about taking that regimen forward. Dr. Roger Cohen presented the monalizumab and cetuximab data in patients with recurrent or metastatic disease in this time in a cohort that were both platinum and PD-1 refractory, so a heavily pre-treated patient population, and very nicely finding a response rate of 20% in patients with squamous cell carcinoma in the head/neck. And then lastly, along the lines of immunotherapy, an update on the data within ICOS agonist GSK3359609 in combination with pembrolizumab in patients who were treatment naïve with head and neck squamous cell carcinoma or at least PD-1 treatment naïve and again finding some promising activity with a response rate of about 24%.

The latter 2 trials, the monalizumab-cetuximab and the ICOS agonist pembrolizumab studies, are in fact now moving on to Phase III studies. And so again, there may be a change in the standard of care using some novel I-O regimens, and it's something to look out for in the future.

Thank you for listening to this review of head and neck cancer abstracts at the American Society of Clinical Oncology Annual Meeting and have a nice day.

ASCO: Thank you, Dr. Cohen.

Next, Dr. Ryan Sullivan will discuss several studies across the field of melanoma treatment. Dr. Sullivan is a medical oncologist and Attending Physician in the Division of Hematology/Oncology at Massachusetts General Hospital. He is also the Cancer.Net Associate Editor for Melanoma and Skin Cancer.

View Dr. Sullivan’s disclosures at Cancer.Net.

Dr. Sullivan: My name is Dr. Ryan Sullivan. I am the associate director of the melanoma program at Massachusetts General Hospital in Boston, and I'm here today to give a summary of some exciting data that was presented at the 2020 Annual ASCO Meeting which, of course, was presented virtually. I have a few disclosures, including that I have served on advisory boards for a number of companies whose data was presented, including Bristol Myers Squibb, Merck, Novartis, and Iovance. I'd like to start, really, by thinking about how a patient's journey with melanoma begins and then moves on through various stages of treatment, because there were a number of very interesting abstracts and presentations presented this year that include important breakthroughs in many different steps in the patient's journey. The first, of course, is a diagnosis, and soon after a diagnosis, often, the next step is surgery.

There's been more and more data about treatment before surgery as a way of potentially improving outcomes for patients who have a significant amount of tumor in place, typically in lymph nodes. Treatment before a planned surgery is called neoadjuvant therapy. There's also been breakthroughs, and, at this year's ASCO, updates on these breakthroughs in treatment after surgery, which is done with curative intent. We call that type of treatment adjuvant therapy. There were some updates to studies in patients who have newly diagnosed metastatic disease, and then there were some very interesting presentations about data of patients who were treated after the first type of treatment, for a patient with metastatic disease, was ineffective, demonstrating some really promising second and even third lines of treatment that may be available for patients.

So I'll start with that neoadjuvant therapy. This is, again, treatment that's given before somebody who could have surgery with curative intent, and the idea behind this is to potentially improve the outcomes of patients. It's also a really important type of research treatment because we can learn a ton about how tumors respond or don't respond to certain types of treatments, and there is a really wide path that's been created by the breast cancer community, who pioneered this type of treatment, and demonstrated that new and effective therapies can actually make it to the standard of care for patients in this setting. In melanoma, we've looked at a lot of the breakthrough therapies that have been approved in the metastatic and the stage 3 after surgery setting, including immunotherapies and BRAF-targeted therapies.

And the background is a number of trials have occurred, and 1 very prominent group that has been leading a lot of these efforts is the group in the Netherlands, and Dr. Christian Blank presented some data on a follow-up study of almost 100 patients, who received a combination of two drugs, ipilimumab and nivolumab, at a schedule in dosing level that had been determined to be, probably, as effective as higher doses and more toxic therapy, but had a better safety profile than other regimens. That trial was called the OpACIN-neo, which randomized patients to 3 different dosing levels and strategies. So patients receive this, and then, in a really cool fashion, they knew that almost 70 or 80% of patients would have a major response to therapy - that was based on other data - but they also wanted to see if they get away with less surgery. And so what they did was, patients who had major responses were offered a smaller surgical resection. Patients who didn't have major responses ended up having a complete surgical resection of lymph nodes, and then they just followed along.

And really, it was less a trial that will prove that this is the right thing to do, but more a trial to be built upon. And as more and more data comes out, this could be a strategy that we utilize for patients, where they may only get 2 doses of a treatment, and then if they have a major response to therapy, they could just be followed closely thereafter. So this trial is called the PRADO trial. Christian Blank was the presenter, and I would say it's promising, and maybe practice-changing as more data comes out and larger trials are performed to compare this strategy with other more standard strategies.

The next set of data that was presented that's really interesting is in the adjuvant setting, so again, these are patients who've had surgery to cure them of their melanoma, but they're at high risk of the melanoma coming back and so receive treatment after surgery - we call that adjuvant therapy - to reduce the chance of disease coming back. There were 2 trials that were updated at this year's ASCO. One was the KEYNOTE-054 trial. This is randomizing a drug called pembrolizumab, an anti-PD-1 blocking drug, versus placebo. This trial was a positive study, and was published a few years back, and pembrolizumab was FDA approved, a few years back, for patients who have high-risk stage 3 melanoma, who have completed surgery. The follow-up data continues to show the superiority of the pembrolizumab compared to patients who received placebo, and importantly, that superiority is across virtually every subgroup that was analyzed, and demonstrates that this approach continues to be a standard approach for patients with melanoma who are high risk and have stage 3 disease that's been resected.

A similar group of patients were enrolled on to a trial called the COMBI-D study. This is a trial that randomized BRAF mutated patients with stage 3 melanoma, whose disease had been removed, and received either dabrafenib and trametinib, which is a BRAF and MEK inhibitor, or 2 placebos. Again, this trial previously read out as a "positive study,” and this regimen has been FDA approved for this patient population. Importantly, the data continues to look really good.

BRAF targeted therapy, initially, it was thought that it might prevent relapse during the treatment time and a little after the treatment time, but there was thoughts that the effects of it, and the effectiveness of it, might actually wane over time, but that doesn't seem to be the case. This is a 5-year update, and it still appears that this combination is associated with cures in patients with stage 3 melanoma, who would not have been cured if they didn't receive it. So again, really important follow-up data, and strengthens the idea that this is a very reasonable alternative to anti-PD-1 antibody therapy like pembrolizumab, which was described just a few minutes before, in the same setting, but in this case in patients who had BRAF mutated melanoma.

There were some important trials, and one was a retrospective study of therapy in patients who had metastatic melanoma or unresectable disease, so this is melanoma that either presented in a widespread fashion, or was previously diagnosed and treated with surgery, maybe adjuvant therapy, and then metastasized. The standard front-line therapy is really 1 of 4 options: anti-PD-1 antibody with either nivolumab or pembrolizumab; BRAF targeted therapy, if a patient has a BRAF mutation; combination nivolumab and ipilimumab; and then enrollment onto a clinical trial.

Many sets of data are out there in publications about the combination of ipilimumab and nivolumab in the frontline metastatic setting, and while it is associated with the highest response rates of immunotherapy in patients with melanoma, it's also associated with very high toxicity rates. And so ultimately, a decision is typically made upfront, and we balance the risk of the toxicities with the benefit of the therapy, and a decision is made about what to give. If a patient receives ipilimumab and nivolumab in the frontline setting, and then their tumor progresses thereafter, there aren't great second-line options unless a patient has a BRAF mutation, and then BRAF targeted therapy with 1 of the 3 BRAF/MEK combinations is an option.

Patients who receive single-agent PD-1 therapy second-line treatment after disease progression-- could be single-agent ipilimumab, which was the first of these new immunotherapies to be approved. And so one of the questions, though, has been could you give combination ipilimumab plus a PD-1 blocking drug in that second-line setting, and have better outcomes than if you just gave ipilimumab? There's no randomized trial looking at this, but a group in Australia did a retrospective analysis and identified patients who received either single-agent ipilimumab, or a combination ipilimumab plus a PD-1 blocking drug. I should say that I was part of this retrospective analysis, and some of our patient data was part of this analysis. What was shown was that there were improvements in the response rate for patients who received combination ipilimumab plus a PD-1 blocking drug, versus single-agent ipilimumab, and it appeared that the benefit was about twice as good, meaning the response rate was about twice as good, and patients had about twice as solid progression-free survival, and they lived twice as long.

Now, any retrospective analysis is really hard to make practice-changing decisions on, we really like randomized trials that are prospective, and so that data doesn't exist. There is a randomized prospective trial currently enrolling patients in the U.S. Cooperative Group setting, and it's randomizing patients, after PD-1 blocking drugs, to either ipilimumab or a combination of ipilimumab and nivolumab. So until that trial reads out, we won't know for sure that this is the right strategy, but the data certainly was suggestive that combination ipilimumab plus the PD-1 blocking drug makes sense. There actually also was data presented in a prospective study, 1 arm, so it wasn't randomized, that patients who'd been on a PD-1 blocking drug and then switched to pembrolizumab, a PD-1 blocking drug, and a low dose of ipilimumab after their disease had progressed on the PD-1 blocking drug. In that study, response rates were in the mid-20% range - I believe it was 27% - which is higher than we've seen with ipilimumab in that setting, for which the response rate would be expected to be about 10-15%. And so again, further data this time, prospective data, suggesting that there is an improved outcome for combination therapy in the second line.

Importantly, toxicity, which we worry a ton about in the frontline, seemed to be less of an issue in the second line because we'd be comparing against ipilimumab, which is more toxic as a single agent than anti-PD-1 blocking drugs is, and in the second line, it seemed like combination therapy didn't seem to be any more toxic than single-agent ipilimumab. I think we also need to see the randomized data to firmly change the standard of care forever, but I think since this is a regimen that can be offered as standard care, with commercial product, it's an option for patients, and there's now data that really supports its use.

The last study I'm going to talk about is a trial of a cellular product called lifileucel. In the '80s and '90s, in the National Cancer Institute, work led by Dr. Rosenberg and his colleagues, in the surgical branch there, developed the technique where they would remove a tumor, take out the T cells from the tumor, grow the T cells, expand them, and then give them back to patients after lymphodepleting chemotherapy, which would allow patients to receive and not destroy those T cells that were coming in, and then give IL-2 to grow those T cells and support them as they expand in the body. This is a very hard therapy to receive. At the NCI, it required patients to have an initial visit, have enough tumor to have it removed, be able to come back a few weeks later, have the tumor removed, and then the T cells had to grow, and we never really knew how many patients ended up showing up at the NCI to be evaluated for this, and then, ultimately, were treated. And so it is hard to know what to make of the response rates, which were remarkably high. As high as 50-55% in some studies when looking at the data. But the worry was that maybe only a quarter of patients that showed up ended up getting treated, and so the response rate would be a lot less, of all people that were screened.

And so there's real interest in finding a commercial product that could not necessarily require the production of the cell product to be done at an individual institution, and certainly not 1 institution like the NCI, but that could be done centrally and commercially. And so lifileucel is a product that comes from patients’ tumors, again, requires a patient to have surgery, the tumor gets removed; it gets sent to a central laboratory where the T cells are isolated, grown, expanded; and then when the product is ready, patients, if they're still well, are able to be admitted to the hospital get lymphodepleting chemotherapy, receive the cells, receive IL-2, and then see what happens. The data that was presented at ASCO was an update from a year ago, which showed that patients-- and all of these patients had had anti-PD-1 antibody therapy, probably 70 or 75% of patients had ipilimumab, so heavily pretreated population of patients, and the response rate of patients who were able to receive treatment was 37%. So that's not everybody, obviously, and that's not even half the patients, but that's a pretty impressive response rate, for patients who weren't previously responding to immunotherapy.

There's a lot of excitement about this data, and more importantly, there was data that suggested that 82% of patients that showed up for surgery ended up getting treated. So we actually have a denominator of patients screened. Ninety-four (94%), 95% of patients were able-- a product was able to be made, so the concerns about whether or not this is for most patients that end up having surgery, the answer is they probably can make a product for just about everybody. This is probably the 1 presentation, in the oral abstract session at ASCO, in the melanoma program, that is a regimen that would be new, and potentially practice-changing in the near future. So that's exciting, and we're hopeful that that will be an option for patients in the near future.

With that, I'd like to finish by saying it was another great year for the melanoma research community. Lots of really interesting data presented. I touched upon some of the highlights, but lots of other really cool trials and data presented, as well, and I remain very hopeful for the future of, not just our research community, but more importantly for our patients, who are going to benefit from this wonderful research that's being done, which will hopefully continue to lead to better outcomes for our patients. And with that, I thank you for your attention.

ASCO: Thank you, Dr. Sullivan. Learn more about the research presented at the ASCO20 Virtual Scientific Program at, and subscribe to Cancer.Net podcasts on Apple Podcasts or Google Play for additional episodes in the Research Round Up series, released throughout the summer.

This Cancer.Net podcast is part of the ASCO Podcast Network. This collection of 9 programs offers insight into the world of cancer care, covering a range of educational, inspirational, and scientific content. You can find all 9 shows, including this one, at

Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds breakthrough research for every type of cancer, helping patients everywhere. To help fund Cancer.Net and programs like it, donate at