2017 ASCO Annual Meeting Research Round Up: Older Adults, Colorectal Cancer, Gynecologic Cancers, and Melanoma

August 17, 2017
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The ASCO Annual Meeting is the premier educational and scientific event where physicians, researchers, and other health care professionals gather to discuss the latest in cancer care and treatment. In today’s podcast, Cancer.Net Associate Editors answer this question: “What was the most exciting or practice-changing news you heard at the 2017 ASCO Annual Meeting?”



ASCO: 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.

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 ASCO Annual Meeting is the premier educational and scientific event where physicians, researchers, and other health care professionals gather to discuss the latest in cancer care and treatment. In today’s podcast, Cancer.Net Associate Editors answer this question: “What was the most exciting or practice-changing news you heard at the 2017 ASCO Annual Meeting?”

First, Dr. Hyman Muss, the Cancer.Net Associate Editor for geriatric oncology, discusses why it’s important for older adults to consider participating in clinical trials, and offers suggestions for patients considering a clinical trial. He also discusses a new study on the impact of advanced cancer on the people who care for older adults, and offers practical advice for caregivers. Dr. Muss is a Professor of Medicine at the University Of North Carolina School Of Medicine, and the Director of the Geriatric Oncology Program at the University of North Carolina Lineberger Comprehensive Cancer Center Program.

Dr. Muss: My name is Hyman Muss, and I am a Professor of Medicine and Director of Geriatric Oncology, which is cancer in older people, at the University of North Carolina at Chapel Hill. This year was a great ASCO meeting, and we had lots of wonderful presentations concerning cancer care in older patients. One of the exciting abstracts and presentations that I saw was presented by Dr. Hapreet Singh, and it was an FDA analysis, a Food and Drug Administration analysis, looking at enrollment of older adults in clinical trials for cancer drug registrations. So these are clinical trials of new agents. And if the clinical trial shows that they're effective, then they get approved by the Food and Drug Administration for use, and all of our oncologists have access to these drugs. And so many of the drugs today that are new and exciting are actually biologic agents, drugs such as pembrolizumab, which President Carter got, which did so well, and some of the new immune modulating agents. And it's interesting, there are very few chemotherapy drugs now, but this abstract looked to see how many older patients got on all these new trials that are being used to register new drugs. And sadly enough, they found that between 2000 and 2015, only a small number of patients in their 70s and 80s got entered on these new trials compared to the number of patients in these age groups who have these diseases.

So this is very concerning because when these drugs are approved, and many of them are, and I see that patient, or your doctor sees a patient who's older and who is a candidate to receive one of these new drugs, we don't have a lot of clinical information on how well older people tolerate them. Do they have more side effects, such as nausea, vomiting, fatigue, other potential side effects? And how do these side effects affect their function, their quality of life on a daily basis? So the message here is that we need more and more older patients who represent the numbers of patients in the population who actually have these malignancies on these trials. And what you can do as a concerned individual is, if you're going to the clinic to see your physician about treatment for cancer or you're a family member, you should ask what clinical trials are available. There's some wonderful information on Cancer.Net that can help provide you with questions, but you should say, "What's available? Am I, or is my family member eligible for the trial? And what are the potential benefits of the trial? What are the side effects? What are the logistics? How many times do I have to come to the doctor, etc.?" But because there tends to be, unfortunately, a persistent bias against putting people who are older on trials, I think you have to be a little assertive and ask the physician or whoever is providing the care about the opportunity to participate. And it's a great opportunity to participate, and frequently, you get exposure to some of the newest and most exciting drugs. So I'd urge you to do it.

The second presentation that I thought was very exciting was done by Sopria Mohealy and her group at the University of Rochester, and they looked at the emotional toll of caregiving for older patients with advanced cancer. These were cancers of all types, and they went out into the community and other settings and asked caregivers and patients about how they were doing with their lives with a diagnosis of cancer.

So they did what's called a geriatric assessment on the patients, and that includes looking at the ability of a patient to function, to do things like care for themselves, to pay their bills, to use the telephone, to go shopping, social support, how many medicines they're taking etc. It's a really good measure of how an older person is getting along in life. And then they look at how are the caregivers doing, were they getting depressed, were they having a hard time caring for the patient, etc. And it was very interesting and very helpful to see, proven, something we probably intuitively know, and that is that the sicker an older person is with their cancer, the more problems they're having, the greater burden on the caregiver. And this isn't surprising but they quantitated it very well. And I think it tells us that if we have a situation where you're a caregiver or you're a patient who has a caregiver that, depending on the needs of the patient, it may be very helpful to intervene and provide the caregivers with tools that can help and take care of the patient.

Frequently the caregivers are unaware of all the social services, physical therapy, meals on wheels, other things that can help the patient. And if they're unaware, and they're stressed out, and they have too much to do, it will lead to depression, to sadness and to other problems that we all experience. So by quantitating this a bit, it allows us to better prepare caregivers to take care of patients who are sick or who are likely to do poorly with their cancer.

And I think what you can do if you're involved in this situation is talk with your physicians about potential resources that can help you at home. Many community and academic practices have social workers that can work with patients and know what resources are available in the region to help them, which can be extremely helpful and very positive. So I think these 2 presentations were among some of the many exciting things that the American Society of Clinical Oncology meeting this year related to caring for older patients with cancer.

ASCO: Thank you Dr. Muss.

Next, Dr. Jeffrey Meyerhardt discusses a large international study that looked at how long people diagnosed with stage III colorectal cancer should have chemotherapy after surgery. Dr. Meyerhardt is the Clinical Director and Senior Physician at the Gastrointestinal Cancer Center at the Dana-Farber Cancer Institute and Associate Professor of Medicine at Harvard Medical School. He is also the Cancer.Net Associate Editor for gastrointestinal cancers.

Dr. Meyerhardt: My name's Jeffrey Meyerhardt. I'm the medical oncologist at the Dana Farber Cancer Center in Boston, Massachusetts, and today I'm going to focus on a trial, or it's actually a conglomeration of 6 trials, that were testing the question for adjuvant therapy for stage III colon cancer, whether receiving 6 months of therapy versus 3 months of therapy would have similar outcomes.

This is actually an international effort of 6 clinical trials. I was actually co-chair of a trial that was being performed in the United States and Canada. And the goal of the effort was to look at whether patients who standardly get 6 months of oxaliplatin and fluoropyrimidine, which was either the drug IV 5-FU or an oral form, capecitabine, could receive 3 months without compromising efficacy and hopefully having less toxicity. The main concern with oxaliplatin is a cumulative neuropathy that affects patients' fingertips and toes, and it can affect function. And what we also know is that this side effect is dose dependent. The less therapy you receive with oxaliplatin, the less likelihood to develop neuropathy and/or the less severity.

So the way the study was done is there were 6 trials that were conducted throughout the world: 4 of them were in Europe, 1 of them in the United States and Canada, and 1 of them in Japan. And they all had the premise of testing 3 months of therapy versus 6 months. It was a randomized effort for each of those trials. They included only patients who had stage III colon cancer. So those are patients who underwent surgery, and at the time of surgery, their cancer was removed, but there were lymph nodes that were removed with the cancer, at least one of them had evidence of cancer in them, and that's considered stage III colon cancer. What we know is that with surgery alone, with stage III colon cancer, the cure rate is about 50%. What we also know is giving chemotherapy can increase that cure rate substantially, to about 70-75% overall.

The standard of care for the past 20 years has been adjuvant therapy with a combination of either 5-FU/leucovorin/oxaliplatin, a regimen called FOLFOX, or capecitabine and oxaliplatin, a regimen called CAPOX. In 5 of the trials there was a choice whether to receive capecitabine/oxaliplatin or FOLFOX. This was not a choice that was randomized. It was either a patient or physician choice. In 1 of the trials, the 1 that was conducted in the United States, the only regimen that was offered was FOLFOX. The trials enrolled patients over a period of 10 years. They didn't all start at the same time. So the one that started the earliest was a trial out of Italy. The one that opened the latest was a trial out of Japan. Each of the trials independently monitored their outcomes, but then there was an agreement to pool all the data from these trials and nearly 13,000 patients were included in this effort.

What we learned was several things. First what we learned is that, 3 months of adjuvant therapy with either capecitabine/oxaliplatin or FOLFOX led to less cumulative neuropathy, in fact about half the amount of cumulative neuropathy compared to receiving 6 months of therapy. And this is neuropathy that can last for multiple years after the completion of therapy. There were also other side effects that were improved including diarrhea and effects on blood counts, but the main one of concern was neuropathy.

In terms of efficacy, there's not a way to show equivalence in medicines and say things are exactly alike. What you say is that 2 treatments are so close to similar that the difference is really nominal. And that's what's called non-inferiority, where you could accept there could be a slight difference between the 2 treatment regimens, but not one to be clinically significant. And in this trial, the goal was to show less than a 2.4% difference in 3-year disease-free survival when you looked at 3 months compared to 6 months. It also uses a thing called a hazard ratio, which is basically the risk of recurrence or death from colon cancer.

And with any statistical measure, there's a range, what's called a confidence interval. And technically the trial did not reach non-inferiority. It did not prove that there was definitively no difference between 3 versus 6 months. However, when we look at 3-year disease-free survival between 3 and 6 months, we see that the absolute difference was only 0.9%. So 1 person out of 100. It's a very small difference when you receive 3 months of therapy versus 6 months in terms of reccurrence and overall survival.

There were then analysis planned to look at several other things. One was what choice of regimen people used, whether they receive FOLFOX or capecitabine and oxaliplatin. Now it was assumed those 2 regimens would be equal because the data from patients who have metastatic disease treated with either regimen shows that they are very similar. However, in this trial, in this effort, we see that those patients who received capecitabine and oxaliplatin, that did meet the definition of non-inferiority, that there was not a statistically significant difference between the two arms that reached the level that we allowed in this effort.

With FOLFOX, the IV 5-FU/leucovorin/oxaliplatin there is more of a difference when you receive 6 months versus 3 months. There was about a 2.4% improvement in disease-free survival at 3 years with 6 months of therapy versus 3 months. We then looked further at the risk groups. So what we know is the two most important factors that affect outcomes of patients with colon cancer is how deep it goes through the bowel wall and the number of lymph nodes involved. And what we found is that patients who had higher-risk disease, 4 or more positive lymph nodes, or where the tumor went all the way through the bowel wall, first, their outcome was worse than those who had either tumor that didn't go all the way through the bowel wall, or only 1 to 3 lymph nodes, but what we also learned is that the difference between 3 and 6 months was much clearer in those patients who had high-risk disease.

So patients who had high-risk disease, 6 months of therapy is preferable, particularly if you receive the IV 5-FU/leucovorin/oxaliplatin regimen called FOLFOX, versus 3 months of therapy. For patients who had lower risk disease, it was clear that CAPOX, capecitabine/oxaliplatin, was non-inferior if you gave 3 months versus 6 months, and though technically not statistically different, the difference when you receive FOLFOX, of receiving 6 versus 3 months of therapy was really nominal.

So the conclusion that I made from the data, and that the authors made from the data, is that there is not one single answer to how the length of therapy that patients receive when they have stage III colon cancer, this really should be risk-stratified and dependent on the choice of regimen used. If patients have higher risk disease, 4 or more positive lymph nodes, all the way through the bowel wall, patients should receive 6 months of FOLFOX therapy. And in my opinion, even with capecitabine and oxaliplatin, should go toward the goal of 6 months of therapy. For patients with lower risk disease, capecitabine/oxaliplatin for 3 months is a very good choice, FOLFOX is also a good choice, and there should be continued discussion how patients tolerating the regimens in terms of neuropathy to determine the length of therapy.

These data are still being analyzed for overall survival, as well as longer follow-up for disease-free survival, and there will be subsequent presentations in later meetings to really understand more about these various risk groups, and in terms of which therapy is optimal for patients. But what we did conclude is that this is a big step forward in not trying to do a one size fits all, and also will hopefully reduce the level of neuropathy of patients in the future who have stage III colon cancer. Thank you very much.

ASCO: Thank you Dr. Meyerhardt.

Next, Dr. Jonathan Berek, the Cancer.Net Associate Editor for Gynecologic Cancers discusses new research on these cancers, including 2 studies that focus on surgery for ovarian cancer, and 2 studies that looked at treatment options for uterine cancer, which is also called endometrial cancer. Dr. Berek is a Professor of Gynecological Oncology and the Director of the Stanford Women’s Cancer Center at Stanford University School of Medicine.

Dr. Berek: This is Jonathan Berek. I am a Professor of Gynecological Oncology at the Stanford University School of Medicine, where I direct the Stanford Women's Cancer Center, and I'm a Senior Scientific Advisor for our Stanford Cancer Institute. Going to speak today about a few of the presentations that were made at the recent Annual Meeting of the American Society of Clinical Oncology on studies related to gynecologic cancers. There are 2 studies that focused on surgery for ovarian cancer, and I think we'll start just to talk about those 2 together.

The first one was a very large study that was done in many sites throughout Germany, which is an area known for doing excellent surgery for ovarian cancer patients. And what was done in a randomized fashion was to study women who were undergoing their primary surgery for ovarian cancer to remove the tumor, and as much metastatic disease as possible in order to improve survival and get them ready for their chemotherapy. What the study did was to look at whether or not removing all of the lymph nodes that are in the pelvis and around the large vessels of the pelvis and the abdomen, the aorta, and whether or not that made a difference in the outcome and, literally, the survival of women after chemotherapy. And it turns out it didn't.

So it was a very important study because it showed that women who had that surgery didn't have to have that part of the surgery done, which can contribute to the side effects of the surgery and prolong the recovery. So what that means, going forward, is that we can now safely omit performing a removal of all of those lymph nodes which, by the way, is in medical terms called the lymphadenectomy. We don't have to do that anymore in patients with what appears to be, otherwise, stage III or IV disease.

In another study, also conducted in Germany and other centers in Europe, the researchers looked at whether or not taking out disease after primary chemotherapy when it was persistent—so what we call secondary cytoreductive surgery. You'll also hear the term, debulking surgery. What it means is that after chemotherapy in some women, what shows up on their scans and follow-up is some persistent areas of disease. And the question is always, should you go back and remove that before initiating another chemotherapy? And what they showed in the study—which, again, was a very large, well done, what we call, randomized study, where they looked at patients where they did the surgery or not. They showed that the surgery did have a positive benefit in certain patients who had small residual disease after chemotherapy, very little fluid in the abdomen and had, what we call, an excellent performance status. So that helps define what we knew from prior retrospective studies that this was important to do, that now we had this large study that confirms that this can benefit some women some of the time.

In another study that looked at women with, what we call, high-risk uterine cancer, endometrial cancer to be specific, which is the most common type of gynecologic cancer in the United States, it's a study that looked at whether or not women who needed pelvic radiation therapy in order to prevent recurrence and to improve outcome and survival, whether if you added chemotherapy during and after radiation therapy—whether that improved the survival. And what the study showed—again, a very large randomized trial, comparing women with or without the chemotherapy, showed that for what we call low stage, or stage I and II disease, that it really didn't benefit to have the extra chemotherapy. Whereas for some of the women with stage III disease, more advanced disease, the chemotherapy did help prolong survival. And it was a significant improvement after five years of 11%, which is a very significant improvement in this particular study.

One more study that was done in endometrial cancer was a chemotherapy study. And this was done in Japan. The Japanese studied whether or not one could use a less toxic regimen of chemotherapy. In this case, 2 drugs that we use frequently for ovarian cancer, carboplatin and paclitaxel, instead of more toxic cisplatin and doxorubicin. And what it was shown is that they were all equally effective, but of course, the less toxic regimen, in fact, caused fewer side effects. So based on that, it means that we can use, now, the less toxic regimen of carboplatin and taxol for women with advanced staged or recurrent endometrial cancer. Thank you very much.

ASCO: Thank you, Dr. Berek.

Finally, Dr. Ryan Sullivan discusses new research on the treatment of melanoma that has spread to the brain. This is called brain metastasis, and can present unique challenges for treatment. Dr. Sullivan is an Attending Physician in the Division of Hematology/Oncology at Massachusetts General Hospital, and the Cancer.Net Associate Editor for melanoma and skin cancer.

Dr. Sullivan: Hello. My name is Dr. Ryan Sullivan. I am the director of translational research in the Center for Melanoma at the Massachusetts General Hospital Cancer Center. I'm here today to discuss some of the exciting findings at the Annual Meeting of ASCO and specifically to discuss some really groundbreaking studies in the field of melanoma, specifically for patients who have brain metastases.

So metastatic melanoma is a challenging disease. Melanoma, generally, is becoming more common. And so we're beginning to see more patients with metastatic melanoma. And, fortunately, over the last decade, there have been some really amazing discoveries that have been translated into effective therapies for patients of metastatic melanoma. And these include immune therapies which target our bodies, a defense system to fight off cancer, and include drugs called ipilimumab and nivolumab, and pembrolizumab. And they also include what we call targeted therapies but really are BRAF targeted therapies, which specifically target a mutation that's present in about 40 or 50 percent of patients called BRAF. In patients who have a BRAF mutation, there are 4 drugs, in 2 combinations of these drugs, which are approved to treat patients. And those drug names are called dabrafenib, trametinib, vemurafenib, and cobimetinib. And we give the combination of dabrafenib and trametinib or the combination of vemurafenib and cobimetinib to select patients with metastatic melanoma who have BRAF mutations.

Now, at the Annual Meeting, there were 3 presentations describing data of clinical trials specifically designed to treat patients with metastatic melanoma who had brain metastases. I think it's important to note that this is groundbreaking, just in and of itself, that there were 3 presentations, which means there were at least 3 trials that were looking at this population of patients. Unfortunately, for many, many decades, patients with brain metastases have been prevented enrollment onto clinical trials. Because when people are designing trials, they often say, "Well, we need to come up with ways of really understanding how well our drug's going to work." And they often exclude patients who are at high risk of developing bad complications. And really, for a long time, patients with metastatic brain metastases kind of fell in that category of patients. However, however, with the advent of these new therapies which I mentioned before, what we've noticed just treating patients with these drugs that we clearly see benefit of these drugs, whether they're the immune targeted therapies or the BRAF targeted therapies in patients that have metastatic melanoma. And in fact, there have been previous presentations and publications demonstrating that BRAF inhibitors like dabrafenib can lead to responses in patients with brain metastases, and immune therapies like ipilimumab can also lead to responses in brain metastases.

And so at this year's ASCO, there were 3 presentations, as I'd mentioned before, 1 with the combination of dabrafenib and trametinib in patients with BRAF mutant melanoma brain metastases. And 2 immunotherapy presentations: 1 with the combination of nivolumab plus ipilimumab in patients with melanoma brain metastases, and another which actually had randomized patients, either nivolumab plus ipilimumab or nivolumab by itself in patients with melanoma brain metastases. The bottom line of all 3 of these trials is that these therapies work. And that's pretty amazing.

In fact, the majority of patients who received the dabrafenib and trametinib combination had responses in the brain. There were 4 different collections of patients that were looked at, including patients who were asymptomatic, patients who were symptomatic, patients who had previously received radiation therapy. And, ultimately, in each of these categories, patients benefited from BRAF MEK inhibitor combination therapy of dabrafenib and trametinib. In fact, the response rates were very similar—maybe slightly lower, but very similar to what we might see in patients who were treated with these drugs who didn't have brain metastases. I think what was really exciting was that this demonstrated, for the first time, the effectiveness of this combination in these patients.

There were also 2, as I mentioned, immune therapy, immune targeted therapy presentations. One of which was the combination of nivolumab plus ipilimumab in the so-called CheckMate204 trial. The data from, I believe, 75 patients were presented at this meeting. And, amazingly, over half of patients responded to therapy. And perhaps more importantly, it appeared that patients who were doing really well at 6 months—and two-thirds of patients didn't have any growth of their disease—seemed to maintain that excellent benefit. This is potentially a very toxic regimen. But importantly, there weren't any new side effects, meaning there weren't side effects related to swelling or side effects related to neurologic side effects that might be seen with these drugs. It didn't seem like treating patients with brain metastases with this combination of ipilimumab and nivolumab led to more side effects than usual. And, generally, it was considered to be well tolerated. And I would venture to say that this combination of therapy, if immune therapy is going to be chosen for patients—and this was patients who had either BRAF mutations or didn't have BRAF mutations—but if a decision is made where the patient with brain metastases could be treated with immune therapy that this combination should be considered strongly as the immune therapy to treat patients with brain metastases.

That statement is actually supported strongly by the results of the third trial that was presented, which is the combination of nivolumab plus ipilimumab in 1 arm of the study, another arm of the study with patients who just received nivolumab. And then, there was a third arm of the study with patients who had a more aggressive disease. And they were treated with nivolumab by itself. But in that randomized part of the study which was comparing the combination of ipilimumab and nivolumab product versus nivolumab by itself, there were double the number of responses. And patients really did much better with the combination, from the standpoint of response and the standpoint of delaying progression, than patients did with just a single agent. And I think what's important to note is that the patients who have disease in their brain, if that disease grows a little bit, it can cause big problems. The head is a confined space. The brain is a critical organ. And so I think having a combination therapy that can lead to more robust response rates and quicker response rates in delaying progression likely will translate into even more benefit than if you have those types of findings in patients who don't have brain metastases. In fact, when you give the combination of ipilimumab and nivolumab versus nivolumab in patients who don't have brain metastases, we do see patients have more rapid responses, higher response rates, and longer time to progression of disease. But patients don't necessarily live any longer. Whether that's true in this scenario, we'll find out over time.

But I really believe that this data and the data from the other study, the CheckMate204 Study, support the use of this combination of ipilimumab and nivolumab in patients who do have metastatic melanoma that is metastasized to the brain. In fact, I think this is 1 of the clear scenarios where this combination, with all the side effects that are increased with it, is worth being used over single-agent nivolumab or another so-called PD1 inhibitor called pembrolizumab.

So that's all I really wanted to cover today. Again, I think the news out of Chicago and ASCO 2017 Annual Meeting with respect to melanoma was, again, a very positive year. Important clinical trials were presented. But truly the 3 trials demonstrating benefit to our standard therapies in patients with metastatic disease to the brain is truly an amazing accomplishment for the reasons I stated. That these are patients that often have been refused entry into clinical trials, that they have 3 trials that have not only been opened and run but completed and showing substantial benefit with these therapies is an amazing accomplishment. And, again, I think another good year for our patients with melanoma in terms of positive findings on critical clinical trials and hopefully another bad year for melanoma. Because it's clear we're getting better at treating the disease. I thank you for your time and attention in listening to this podcast. Have a great day.

ASCO: Thank you Dr. Sullivan.

To learn more about all of the science presented at the 2017 ASCO Annual Meeting, visit www.cancer.net/ascoannualmeeting. If you have questions about whether new research may affect your care, be sure to talk with your doctor.

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