2017 ASCO Annual Meeting Research Round Up: Brain Tumors, Childhood Cancer Survivorship, Head and Neck Cancer, and Prostate Cancer

July 25, 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. Susan Chang discusses the importance of precision medicine in the field of central nervous system tumors. Dr. Chang is the Director of the Neuro-Oncology Division at the University of California, San Francisco, and the Cancer.Net Associate Editor for Central Nervous System Tumors.

Dr. Chang: Hello, my name is Susan Chang, and I am the director of the Division of Neuro-Oncology at the University of California in San Francisco. I also serve as the editor for the cancer.net portion that relates to brain tumors, and I'm very pleased to give you an update on the findings and reports regarding progress in brain tumor research that was held at the annual American Society of Clinical Oncology meeting in Chicago in 2017.

The theme for this meeting was, "Making a difference in cancer care for you." And for the central nervous system tumors, the highlights really focused on the advances in our understanding of the genomic make-up of tumors and how that can affect how we care for patients. So in addition to being able to better predict the natural history of these tumors in a much more uniform manner, the molecular and genomic makeup can also inform us on avenues for developing new treatments. More importantly, the hope of identifying groups of patients who may benefit from a targeted approach to care brings us closer to the ideal of precision medicine, that is, the right treatment for the right patient at the right time.

Several brain tumor types were highlighted, and one session reviewed the new classification for childhood tumors and the implications for diagnosis and treatment. The classification of tumor types is medulloblastoma, ependymoma, and glioma in children and have profound effects with clinical trial approaches, specifically targeting subgroups of these patients. For example, it is known that a certain subset of medulloblastoma patients can be associated with very good prognosis and an expected long-term survival and in this group of patients, optimizing the intensity of treatment to minimize side effects while not compromising survival is a very important goal. In addition, because specific mutations can be present in midline gliomas, not only can this be a diagnostic tool, but therapeutic strategies are now being developed specifically against this particular mutation.

In the adult setting, the section on innovative targeted therapeutic approaches in brain metastases, that is tumors that arise outside of the brain from other organs that may spread to the brain, this is reviewed with the recently completed and ongoing clinical trials that use agents specific to an aberrant segment pathway in lung cancer, melanoma, and breast cancer. For primary brain tumors, an education session reviewed strategies beyond standard chemotherapy for glioma and highlighted the challenges of specifically targeting pathways that can be abnormal. The presentation of the glioma cohort of the NCI-led MATCH trial showed this proof on concept of enrolling patients based on common genomic features, irrespective of the actual tumor type. In addition, the results of a clinical trial of meningioma using targeted therapies were reviewed.

The need for improved therapies beyond precision-based approaches were also highlighted. We all know that the blood-brain barrier can play a major role in preventing high enough concentrations of agents to reach the tumor to have an effect, and there were several were presentations that discussed early results of these novel strategies of delivery. A safety study of a radio labeled monoclonal antibody was administered by a catheter infusion into the brainstem of patients with glioma using what we call a convection-enhanced delivery system. And this is where a pressure pump is applied to the catheter, and the drug is convected directly into the tumor tissue. And this demonstrated that in addition to it to being very well-tolerated, it also had the advantage of being able to be tracked because of the radioactive material that was used with the antibody, and so using PET imaging, the actual tracer could be visualized to make sure that the drug got where it needed to go into the brain stem.

Another approach that was discussed was the direct injection of a virus that could multiply specifically in tumor cells and not normal cells, thereby killing the tumor cells and sparing normal tissues. And because these viruses can spread locally into dividing cells in the brain, the systemic effects are minimized.

Harnessing the immune system to fight cancer has been the most recent approach that's been successful in cancer such as melanoma and kidney cancer, and this strategy is also actively being pursued in the most malignant primary brain tumor glioblastoma. And this was a topic of several educational sessions as well as original abstracts presented at the meeting. There was one study in particular, which was a phase III trial of a personalized peptide vaccination in specific patients with recurring glioblastoma, and this was presented by Dr. Terasaki on behalf of 20 Japanese hospitals. So patients were either given the vaccine treatments versus best supportive care, and these vaccines were chosen from 12 specific proteins based on the characteristics of the immune system for the patient. Now, in this study, there was no difference in the survival in general of patients treated with the vaccination versus standard of care, however, the investigators did propose several factors that might've accounted for this, and when they did a sub-group analysis in a certain cohort of patients, they did see some improvement of survival compared to best supportive care, suggesting that patient selection is going to be very important in terms of assessing this types of strategies.

So it was very exciting overall to see some of the approaches that are being tested in patients with brain tumors and to recognize and thank the investigators and most importantly the patients who participated in these studies as partners with the scientists. Thank you.

ASCO: Thank you Dr. Chang.

Dr. Melissa Hudson, the Cancer.Net Associate Editor for Childhood Cancer, also discusses this new research on brain tumors in children, as well as results from the Childhood Cancer Survivor Study on long-term side effects of cancer treatment. Dr. Hudson is Director of the Cancer Survivorship Division, and Co-leader of the Cancer Prevention and Control Program at St. Jude Children's Research Hospital in the Department of Oncology.

Dr. Hudson: This is Dr. Melissa Hudson from St. Jude's Children's Research Hospital. I direct the Cancer Survivorship Division in the Department of Oncology. The 2017 American Society of Clinical Oncology meeting had common themes among studies presented in the pediatric oncology sessions. Several studies presented results of trials testing new therapy approaches for pediatric cancer that had failed to respond to traditional treatments like chemotherapy and radiation therapy. Newer therapies are targeting cancer-remoting gene changes that control cancer cell growth. Pediatric Brain Tumor Consortium investigators reported outcomes for children treated with Selumetinib, a protein kinase drug that targets BRAF, a cancer-promoting gene change or mutation that has been identified in many types of adult-onset cancers. Selumetinib was tested for activity in children with recurrent and unresponsive brain tumors. Responses for children enrolled on this trial were very promising, and the study continues with this agent.

In another study looking at molecular changes in cancer cells, researchers from Sick Kids in Toronto analyzed biopsy assessments from over 800 children with low-grade glioma brain tumors. They discovered what they called driver events or cancer-remoting gene changes in the brain tumor cells that were linked to the specific type and location of tumor and its response to therapy. Again, BRAF mutations were the most common molecular changes identified in the low-grade gliomas. Because information about molecular alterations can help predict how well the brain tumor will respond and help identify new treatment options, these investigators encouraged biopsy of low-grade glioma brain tumors to guide decisions about the type of therapy.

Another promising new therapy is being tested in children with cancer called Chimeric Antigen Receptor Modified T-cell therapy, or CAR T-cell therapy for short. CAR T-cell therapy involves taking T-lymphocytes, a type of white blood cell important for immunity, and linking it to a specific antibody protein against the cancer cell. The CAR T-cells are given back to the patient where it can specifically target and kill the cancer cells. Researchers from the Children's Hospital of Philadelphia presented result after CAR T-cells targeting the CB19 protein on leukemia cells were given to 60 children with relapsed leukemia, who had failed to respond to multiple therapies. Responses were remarkable, with 93% of children achieving a complete response by day 28, and all of 80% surviving one year after therapy. These CAR T-cell were made from mouse sources. So now they're also studying similar CAR T-cells made from humans to avoid reactions to the mouse proteins. Early results for human-derived CAR T-cells showed durable responses in children with leukemia, relapsing outside the bone marrow. CAR T-cells are also being tested in children with unresponsive solid malignancies. Researchers from Baylor College of Medicine presented result from a CAR T study targeting a protein on sarcomas, human epidermal growth factor receptor or HER2. This study showed that CAR T-cells linked with an antibody against HER2 were safe and induced responses in patients with heavily treated and unresponsive sarcoma.

The results of these targeted and CAR T immunotherapy approaches offer hope for children with unresponsive cancers. Ongoing research will help clinicians understand which children can most benefit from these new treatments and how to use them with other standardly used therapy like chemotherapy and radiation therapy. Several studies presented evidence about the progress that has been made in reducing health problems after cancer known as late effects. Overall, this progress has involved research, linking specific treatments with specific late effects, identifying who is at highest risk for the health problem based on their age, sex, race, type or dose of therapy, and then changing therapieswhen at all possibleto reduce these risks.

Researchers from the Childhood Cancer Survivor Studya study tracking the health of survivors treated at 31 pediatric cancer centers in North Americapresented results of a study that showed that younger children were at much higher risk for heart problems after receiving treatments with anthracycline chemotherapy, or chest radiation, known to be toxic to the heart. Also, survivors who were treated with combinations of these cardiotoxic chemotherapy and radiation therapy had a higher risk of coronary artery disease. In another study, St. Jude investigators identified a specific gene change that was associated with a marked increased risk for premature menopause in women treated with radiation to the ovaries. These results are important for clinicians and cancer patients and their families to consider at diagnosis when treatment is being planned and after completion of therapy when survivors are being monitored for health problems during long-term follow-up. Just how impactful late effects research has been was reported in another childhood cancer survivor study that asked over 20,000 survivors treated for childhood cancer from 1970 to 1999 about their current health problems. They reported that the rate of severe, disabling, and life-threatening chronic health problems declined steadily from 1970 to 1990, with less than 10% of survivors treated during the 1990s reporting that they had serious late effects like a second cancer. The lower risk of chronic health problems was seen in survivors of Wilms' Tumor, Hodgkin's and non-Hodgkin's lymphoma, Astrocytoma, and Acute Lymphoblastic Leukemia. These results remind us that important progress can be made from research collaborations between clinicians, scientists, childhood cancer patients, and their families.

ASCO: Thank you Dr. Hudson.

Next, Dr. Ezra Cohen discusses 1 study that paves the way to helping reduce an increasingly common type of cancer, and as well as new research on treatment options for head and neck cancers. Dr. Cohen is Associate Director of Translational Science and team leader in Head and Neck Oncology as well as the Solid Tumor Therapeutics research program at Moores Cancer Center at UC San Diego Health. He is the Cancer.Net Associate Editor for head and neck cancer.

Dr. Cohen: Hi, I'm Ezra Cohen. I'm a medical oncologist at University of California San Diego Moores Cancer Center. I'm going to be talking to you today about recent findings and discoveries at the American Society of Clinical Oncology annual meeting that just took place in early June 2017 in Chicago. I'm going to focus my comments on head and neck cancer and start with some interesting findings around HPV preventative vaccines. We've known for some time that these vaccines have been approved for both men and women to try and prevent high-risk HPV infections. For women, they've been approved to prevent cervical cancer, and for men, they've been approved to prevent genital warts. We think that the vaccines should have an effect as well on oropharynx cancers, which we now know can be related to HPV infection, human papillomavirus, especially the high-risk strain of HPV-16. And most concerning, it's a cancer that is rising in incidence in the United States and several countries around the world. The thought is that if we were to vaccinate individuals prior to sexual activity, that we would be able to begin to reduce the incidence of this cancer, and even in a perfect world, prevent these cancers altogether. We are beginning to see such data emerge, at least very early, in other countries where universal vaccination programs have already taken place.

At the ASCO Annual Meeting, Maura Gillison and her colleagues presented population data from the United States looking at individuals who were vaccinated. Again, these are voluntary vaccinations, not universal programs. And what they demonstrated was that the risk of infection, at least an oral HPV infection with a high-risk strain is reduced dramatically in both men and women who receive the vaccination. In fact, the risk of infection in men was reduced about tenfold. In other words, to put this into perspective, if men and women were to be vaccinated with the HPV vaccines, their risk of contracting a high-risk HPV in the oral cavity went down about 10 times, which in the vaccine literature demonstrates a dramatic effect on the risk of infection. Of course, we don't know how this would translate into the risk of cancer, but we do know that a precursor to developing an HPV-related oropharynx cancer is infection. And so the hope is that vaccination would be able to dramatically reduce the incidence of these cancers in the future.

Moving from preventing the disease to treating the disease, we saw data from a few different abstracts looking at dosing of a common chemotherapy drug called cisplatin in the context of radiation. And although there is some controversy in the interpretation of those studies, it does look like they proved the utility of a so-called old-fashioned regimen that is of high-dose cisplatin given every 3 weeks. This has been an area that has been contested among treating centers and especially medical oncologists for really the last decade, and now we have prospective data to demonstrate that the every-three-week high-dose cisplatin appears to be as well tolerated, and in some cases, more effective than the weekly cisplatin.

Then, lastly, the other big splash at the Annual Meeting was around immunotherapy and a few different abstracts presented in that context. Most relevant for treatment was a combination of a PD-1 antibody called pembrolizumab combined with an IDO inhibitor called epacadostat. And what the investigators demonstrated in patients with head and neck cancer who were refractory to treatment, who had received either 1 to 2 prior therapies, that the response rate was about 40%. To put into context, that's about double what we would expect with pembrolizumab alone, and more than double what we would expect with more conventional chemotherapy or cetuximab in these patients, suggesting that the combination for at least a good proportion of patients was very effective.

The other thing that was really nice to see from this abstract is that many of the responses were complete or close to complete responses. In addition to that, we saw some more data on immunotherapy in head and neck cancer. We saw data using it in patients with locally advanced disease who had never been treated that looked very promising in terms of its effect. Those data were really too premature to think about how effective this will be ultimately, but at least we did see that it was safe to use in that upfront setting. And then, lastly, we saw data around biomarkers that may suggest to us which patients benefit the most from immunotherapy, and now those are being taken forward into prospective studies.

In conclusion, the ASCO meeting was another great success in terms of moving the field forward, this time with respect to trying to prevent the disease with an HPV vaccine, trying to better treat patients who have locally advanced disease, and then ultimately trying to develop new therapies to treat patients who don't respond to current treatment. Thank you very much.

ASCO: Thank you, Dr. Cohen.

Finally, Dr. Brian Rini discusses 2 related studies in advanced prostate cancer. Dr. Rini is a Professor of Medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University and a staff member of the Department of Solid Tumor Oncology at Cleveland Clinic Taussig Cancer Institute. He is also the Cancer.Net Associate Editor for genitourinary cancers.

Dr. Rini: Hi, this is Dr. Brian Rini from the Cleveland Clinic Prostate Cancer Institute. And I'm going to comment today on 2 very important studies in advanced prostate cancer that were presented at the ASCO 2017 Annual Meeting. One of these was a plenary session study and the other was presented in the oral prostate session. And these really are sort of immediately practice impacting, which is exciting for those of us in the field who take care of these patients. The first study was called a LATITUDE study, and this was presented at the plenary session this year. And this was a randomized study that took men with newly diagnosed high-risk advanced prostate cancer and randomized them to either hormone therapy alone or hormone therapy plus abiraterone acetate, which is a second-generation hormonal therapy that was approved in the last few years for advanced disease.

The background of this study is that hormone therapy for advanced prostate cancer—that is, prostate cancer metastatic to bones or other organs—has been the standard of care for many, many decades. But that hadn't changed until recently a few years ago at a different plenary session, Dr. Sweeney presented a CHAARTED study, which investigated the addition of chemotherapy to upfront hormone therapy and showed a significant survival advantage. And this was supported by other large studies in the field. And so from that time a couple years ago, the standard shifted from simply hormone therapy to hormone therapy plus chemotherapy, although this benefit seemed to be largely confined to those with high-volume disease as defined in the protocol with 4 or more bony lesions. And so the field sort of evolved from giving everyone hormones to giving everyone hormones plus chemotherapy in a subset of patients. And so it was on this background that the LATITUDE study was conducted and now reported recently, again, randomizing men with high-risk prostate cancer to either hormones or hormone plus abiraterone.

The investigators defined high risk in this study differently than the chemotherapy studies to include at least 2 of 3 high-risk criteria, that is a Gleason score of 8, and the presence of 3 or more bone lesions on a bone scan, or the presence of visceral lesions such as in liver or lung. Patients were equally randomized, and the co-primary endpoints were overall survival and radiographic progression-free survival with a bunch of important secondary endpoints. This is a large global multi-center study conducted at over 200 sites across the world. This is really a well-designed study prospectively designed to look at these primary endpoints.

The radiographic progression-free survival favored the addition of abiraterone to initial hormones in this high-risk population. The median time was 33 months in the investigational arm compared to approximately 15 months in the hormones alone arm. So the hazard ratio of 0.47 with, as you can imagine, a highly significant p-value. These curves split fairly early on at about the 3-month mark and stay split really throughout their course out beyond 3 years from the data presented at ASCO.

The other important primary endpoint was overall survival. And this study also showed a significant advantage in overall survival. The hazard ratio for benefit for the investigational arm with the addition of abiraterone was 0.62, i.e. a 38% risk reduction of death. The overall survival rate at 3 years was increased by about 17% in the investigational arm. And the median had not even been reached in the investigation alarm and was about 35 months in the hormone alone arm, which is consistent with prior studies, including the CHAARTED study that had looked at hormones alone in a similar, but not identical, population of patients. So the summary of this study was that the addition of abiraterone to standard hormones for men with, as they defined, high-risk advanced prostate cancer significantly increased the time to radiographic progression and increased the time to death. Really very impressive clinical results. Not only statistically significant, but clinically quite impressive.

Another study that was presented at ASCO in the prostate oral session was the STAMPEDE study. The STAMPEDE study is a British multi-arm study that had also previously reported on the addition of chemotherapy in this population much as CHAARTED had, that I mentioned earlier. And without going into the full details, this was a little bit of a different study in that there was also patients with high-risk localized prostate cancer included. So a bit of a broader spectrum of patients. Not just patients with a bone or visceral metastatic disease but also showed similar benefits in terms of radiographic progression-free survival and overall survival. So really, supportive of the LATITUDE studies that I discussed first. So this has sort of turned the world of treating initially metastatic advanced prostate cancer on its ear a little bit. And now the question is how do we integrate both additional hormone therapy, i.e. abiraterone, and additional chemotherapy for patients who are presenting?

If you look across studies, all the studies that I've mentioned, again, the control arm for the hormones alone perform very similarly both in terms of radiographic progression-free survival and also overall survival. And therefore, although the populations were defined differently in each protocol, the prognostic makeup and the clinical makeup of patients who were involved appears to be quite similar, at least based on outcome.

And the magnitude of benefit for chemotherapy and for the addition of abiraterone in the setting is also quite remarkably similar in terms of the hazard ratio for overall survival was 0.62 in the LATITUDE study, 0.63 in the CHAARTED study. The 3-year overall survival rates are very similar. Disease control is very similar. So again, similar control populations and similar investigational populations. So the natural question is how do we integrate these new data for a patient presenting today with advanced prostate cancer?

I think that question remains to be determined, likely through further studies that look at perhaps standard hormones, plus abiraterone, plus or minus chemotherapy. I think in just discussing with my clinical colleagues how they're going to interpret these data, I think most people certainly feel that abiraterone would be better-tolerated therapy to add on, so if the benefit is similar, I think would lean towards adding an additional hormone therapy as opposed to adding chemotherapy. To balance this, however, the chemotherapy is 6 cycles. So it's over in roughly 18 weeks, whereas patients who were on abiraterone in the LATITUDE study for not quite 3 years. So perhaps chemotherapy is trading off some upfront, initial toxicity that may be more severe compared to a more chronic therapy, such as having to be on abiraterone for 3 years. This also doesn't speak of the cost of therapy. The cost of adding 3 years of abiraterone is likely going to be greater than the cost of adding initial chemotherapy, and so especially in non-US countries, where reimbursement of drugs is a larger issue, this may come into play as the therapies get integrated into clinical practice.

I think probably the way it's going to play out is that for patients who meet the LATITUDE definition of high-risk, the addition of abiraterone is reasonable. I think most people have a gut feeling, not necessarily supported by data yet, that for patients with visceral disease, higher volume disease, more than 4 bone metastases, and maybe more adverse prognostic features, that perhaps chemotherapy is a better choice. And all this, of course, is predicated on reimbursement of abiraterone, as I mentioned earlier, even in the US, that's not quite worked out because the label has not been changed. So it's really a very fluid situation and where people are going to have to make clinical decisions on a patient-by-patient basis. Personally, I'm reassured that either offers patients would appears to be similar benefits, and again, there may be specific patients based on co-morbidities or toxicity profile, where one or the other is more apt for that particular patient. But I sense that pending reimbursement that abiraterone will likely become the standard of care in most patients with chemotherapy as a suitable alternative, as discussed.

Certainly, it's an exciting time for prostate cancer. Hormone therapy has been around for many decades, and that initial approach hadn't changed in many decades, but now in a span of 5 years, we have 2 plenary discussions, and 4 or 5 very large studies that have very much changed the standard of care and improved both disease control and survival in this very common group of patients. Thank you.

ASCO: Thank you Dr. Rini.

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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