The 2019 ASCO Annual Meeting, held May 31 to June 4, brought together physicians, researchers, patient advocates, and other health care professionals from around the world to present and discuss the latest research in cancer treatment and patient care. In the annual Research Round Up podcast series, Cancer.Net Associate Editors share their thoughts on the most exciting scientific research to come out of this year’s ASCO Annual Meeting and what it means for patients. This podcast covers research in breast cancer, head and neck cancer, and care for nausea and vomiting.
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The 2019 ASCO Annual Meeting, held May 31 to June 4, brought together physicians, researchers, patient advocates, and other health care professionals from around the world to present and discuss the latest research in cancer treatment and patient care. In the annual Research Round Up podcast series, Cancer.Net Associate Editors share their thoughts on the most exciting scientific research to come out of this year’s ASCO Annual Meeting and what it means for patients.
First, Dr. Lynn Henry will discuss 3 studies that explored new treatment options for women with breast cancer, including a study on immunotherapy for triple-negative breast cancer and 2 studies on treatment for hormone receptor positive, HER2-negative breast cancer. She also discusses research on the effects of a low-fat diet in women diagnosed with breast cancer, and a study on whether pregnancy after breast cancer increased the risk of recurrence.
Dr. Henry is an Associate Professor and Interim Division Chief of Oncology in the Department of Medicine at the University of Utah and Director of Breast Medical Oncology at the Huntsman Cancer Institute. She is also the Cancer.Net Associate Editor for Breast Cancer.
Dr. Henry: Hi. My name is Dr. Lynn Henry. I'm a medical oncologist who specializes in treating breast cancer at the University of Utah. Today, I'm going to discuss research on breast cancer that was presented at the 2019 ASCO Annual Meeting in Chicago. In particular, I'm going to focus on the results of some clinical trials that directly impact how oncologists treat patients with breast cancer. First, I'm going to give just a very brief overview of the types of breast cancer and then talk about some research that was presented on triple-negative and hormone-receptor-positive breast cancer. Then I'm going to briefly review findings related to diet and breast cancer as well as pregnancy after breast cancer in women with BRCA mutations.
As a quick reminder, there are multiple kinds of breast cancer. Some breast cancers are called hormone-receptor positive or estrogen-receptor positive, and those are stimulated to grow by estrogen. We treat those cancers with anti-estrogen treatments or anti-hormone treatments to block estrogen or lower the estrogen level in the body. Other breast cancers are called HER2-positive. These are often more aggressive cancers. But because they have extra copies of HER2, they often respond to treatments that block HER2. And finally, there are breast cancers that don't have hormone receptors or HER2, and these are called triple-negative breast cancer.
So first, I'm going to focus on this type, triple-negative breast cancer. Until recently, most of the time, we treated triple-negative breast cancer with chemotherapy because we hadn't found other drugs that worked very well. There's a new type of drug, however, called immunotherapy that tries to use a patient's immune system to help fight the breast cancer. Early in 2019, the FDA approved a new treatment for triple-negative breast cancer that is a combination of a chemotherapy called Abraxane and a new immune drug called atezolizumab or Tecentriq. The combination increased the length of time until cancer progressed or grew. Overall, the treatment was fairly well tolerated. But we did learn that in order for the treatment to work, the cells surrounding the cancer have to have at least a small amount of a very specific protein called PD-L1.
So at this recent ASCO meeting, we heard an update about this treatment. In the trial, the patients whose cancers had the PD-L1 protein and who got the combination treatment lived 7 months longer than those who got just the chemotherapy, which was an increase from 18 months to just over 2 years. This is an important first step towards finding a better treatment for this difficult type of triple-negative breast cancer. And this treatment is currently available to patients. Additional clinical trials are going on now to try to find even better combinations of chemotherapy and immune therapies to treat this type of cancer.
So next, I'm going to talk about hormone-receptor-positive breast cancer. There were two trials of this type of cancer that had important results presented at the ASCO meeting. First, I'll focus on the treatment of early-stage node-negative breast cancer that is hormone-receptor positive and HER2 negative. The Oncotype DX test is a test we commonly run on tumors of this type to help determine whether treatment with chemotherapy is likely to be helpful. For this test, if your tumor has a score over 25, then chemotherapy is generally recommended in addition to anti-hormone therapy. If you have a score under 11, then chemotherapy is not recommended and a patient should receive only anti-hormone therapy. But for those with scores between 11 and 25, it was unclear how beneficial it was to receive chemotherapy. Last year, the results of the TAILORx trial were reported. And that showed that for women over the age of 50, if their tumor had a score between 11 and 25, they were not likely to get benefit from chemotherapy. However, it turned out it was a bit more complicated for women aged 50 and under. For those with scores between 11 and 15, chemotherapy was not likely to be beneficial. However, for those who score 16 to 25, chemotherapy might be beneficial. So we got some answers but not everything.
At this recent ASCO meeting, additional information was reported to help guide treatment decision making for this middle group of women aged 50 and under. So for women whose scores were at the higher end, 21 to 25, chemotherapy was found to be likely to be beneficial. However, in that middle group, the 16 to 20 group, chemotherapy might be beneficial but generally only for women with higher risk cancers, meaning larger cancers or higher grade. This information is helpful because it provides more information for oncologists and for patients when they are discussing whether or not chemotherapy should be included as part of their treatment.
So switching gears a little, still staying with premenopausal women and hormone-receptor-positive HER2-negative cancer, but now thinking about metastatic breast cancer, so cancer that has spread. We now have additional information about treatment with an anti-hormone therapy plus an additional drug called the CDK4/6 inhibitor. We've routinely been recommending this treatment combination because it leads to a longer time before the cancer progresses. But until now, we didn't know if it actually allows women with this type of cancer to live longer. The results of the MONALEESA-7 trial, which looked at the combination of an anti-hormone therapy plus the drug called ribociclib, showed that women who received the combination instead of anti-hormone therapy alone live almost 30% longer. So looking at women 3 and a half years after they started treatment, just over 70% of the women who were treated with ribociclib plus anti-hormone therapy were alive compared to just under half of women treated with anti-hormone therapy alone. So these results reinforce that this is an excellent first approach to treatment of premenopausal women who have newly diagnosed, hormone-receptor-positive HER2-negative metastatic breast cancer.
So in addition to studies looking at these specific types of breast cancer, there were 2 other interesting studies that were applicable to breast cancer more generally. So there was a large study that was reported that looked at whether having a low-fat diet reduced the likelihood of developing triple-negative breast cancer. So in this study, postmenopausal without cancer were randomized to either a low-fat diet or their usual diet and followed for many, many years. Over time, some of these women developed breast cancer with no difference between those who followed the low-fat diet or the regular diet. However, in this new report, they looked specifically at the women who developed breast cancer who were enrolled in this trial. Fewer women died from their breast cancer if they ate the low-fat diet, especially if they had preexisting high cholesterol, diabetes, and obesity. These findings suggest that having a low-fat diet may actually reduce the risk of dying overall and also specifically from breast cancer. Now, these need to be validated, and we don't quite understand why this would be the case. But in general, it seems like having a low-fat diet, avoiding high cholesterol, diabetes, and obesity is a good thing.
And then finally, 1 question that comes up often is whether it is safe to have a baby after the diagnosis of breast cancer. This is especially concerning for patients who have a mutation in genes called BRCA1 or BRCA2 since those mutations greatly increase their risk of developing both breast and ovarian cancer and also leads to the diagnosis of breast cancer at an early age. In addition, patients with these mutations are often recommended to have their ovaries removed at a young age. So in this study, patients who became pregnant did so about 4 and a half years after they were diagnosed with breast cancer. There was no apparent increase in miscarriage, preterm birth, or birth defects compared to what would be expected in women without cancer. And in the patients, there was no increase in the risk of breast cancer recurrence compared to those who did not become pregnant. And in fact, those who became pregnant were slightly less likely to have their cancer return, especially those who had mutations in BRCA1. So while there are some limitations to the study, the findings are reassuring that there does not appear to be an increase in risk of breast cancer returning in these patients with BRCA mutations who become pregnant after breast cancer diagnosis.
So overall, as you can see, there's a lot of exciting research going on across all the different subsets of breast cancer. The results of many important clinical trials were reported at the recent ASCO meeting, and there are many more trials ongoing that will hopefully result in the approval of multiple new effective treatments for breast cancer. In addition, there's research going on examining the impact of treatment on patients with breast cancer and trying to improve the lives of those living with breast cancer. Clinical trials are critical for the development of these new treatments.
Well, that's it for this quick summary of this important research from ASCO 2019. Overall, we continue on a fast track in breast cancer, with many new and exciting therapies being actively studied and research helping support our patients do better than ever before. Stay tuned to Cancer.Net for future updates from upcoming breast cancer conferences. Thank you very much.
ASCO: Thank you, Dr. Henry.
Next, Dr. Ezra Cohen will discuss several studies that looked at using immunotherapy and targeted therapy to treat different types of head and neck cancer. Dr. Cohen is Associate Director of Translational Science and leads 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 Dr. Ezra Cohen from UC San Diego Moores Cancer Center. Today, I'm going to talk about research on head and neck cancer that was presented at the 2019 ASCO Annual Meeting. I think the most impactful presentation at the meeting was a follow-up on the KEYNOTE-048 study, which implemented the drug pembrolizumab, an anti-PD-1 antibody in first-line recurrent metastatic head and neck cancer. These were patients who were treated with curative intent or presented with metastatic disease, and either way, either had recurrence or eventually developed metastases.
The first-line standard of care for these patients used to be the so-called extreme regimen, which involved platinum, 5-FU, and cetuximab. This was validated in an earlier phase III study that was conducted about 10 years ago and was the approved first-line regimen for these patients. In KEYNOTE-048, this extreme regimen was tested against either pembrolizumab alone or pembrolizumab, platinum, and 5-FU, in other words, substituting cetuximab for pembrolizumab in one of the experimental arms.
We'd initially seen the interim analysis data at last year's ESMO meeting, but this year, we have the final analysis presented at ASCO. And what we saw was that both experimental arms actually achieved an improvement in overall survival compared to the extreme regimen. Interestingly, for pembrolizumab alone, this occurred in patients whose tumors expressed some level of PD-L1. That was evaluated by something called the composite score and takes into account both stromal and tumor cell staining of PD-L1. In fact, even at a very low level—that is CPS greater than or equal to 1—pembrolizumab monotherapy was superior to the extreme regimen with respect to overall survival. For all patients, the regimen of pembrolizumab plus chemotherapy was superior to the extreme regimen irrespective of PD-L1 staining.
What we saw at this year's ASCO meeting was that, in fact, first, the higher the expression of PD-L1, the greater the benefit one derived from pembrolizumab either as monotherapy or in combination with chemotherapy. And in patients who had higher levels of PD-L1 and received both pembrolizumab and chemotherapy, the overall survival was quite remarkable with a hazard ratio of just higher than 0.6. In fact, we now have FDA approval in the United States for pembrolizumab monotherapy with tumors that have some expression level of PD-L1—that is CPS greater than or equal to one—or for all comers in patients who either the CPS status is unknown or patients whose tumors don't express PD-L1.
Beyond KEYNOTE-048, we saw interesting data in first-line recurrent metastatic using a regimen of taxane, platinum, and 5-FU compared to the same extreme regimen that we just mentioned. That regimen turned out to be much better tolerated with fewer adverse events but with no improvement in overall survival, giving us a regimen that we could substitute for the extreme regimen if one wanted to, realizing that it does not involve immunotherapy, and for some patients, this may still be an appropriate treatment.
Beyond the first-line recurrent metastatic studies, we saw a few interesting trials looking at targeted therapy in head and neck cancer but specific subsets. The first was in patients whose tumors expressed HER2 at very high levels—that is HER2 amplified—and had salivary ductal carcinoma. We've known that a proportion of salivary ductal carcinoma patients' tumors amplify this gene, HER2, similar to breast cancer and some other malignancies and that trastuzumab may, in fact, be effective. Well, in this study conducted by the Memorial Sloan Kettering Group, an antibody-drug conjugate trastuzumab emtansine was employed as a single agent in these patients whose, again, tumors amplified HER2. And what they saw was a remarkable 90% response rate. Now, this was only in 10 patients, so the study is small, but I think it's safe to say that this drug appears to be quite effective in patients with HER2-amplified salivary ductal carcinoma.
Along those lines, in the subset of thyroid cancer patients whose tumors either mutate or have a RET fusion, the gene RET, there appeared to be very high efficacy for a novel agent that targets the RET oncogene. This was in both patients with medullary thyroid cancers that often have a RET mutation or in papillary thyroid cancers whose tumors often have a fusion of the same RET gene. Again, underscoring the idea that if we can target a driver even in a relatively small subset of patients, the benefit may be quite large. Along those lines, we had seen prior data for track inhibitors in patients who have in track fusions. And again, this applies to subsets of head and neck cancer patients that have either salivary gland cancers or thyroid cancers.
Lastly, we continue to see emerging promising data of combinations with immunotherapy, and 2 highlights from ASCO were pembrolizumab with cetuximab showing a response rate of over 40% in a small group of patients and pembrolizumab with a TLR9 agonist called SD-101 showing about a 30% response rate. Of course, these data are very early and uncontrolled, and so we have to follow these stories further along to see if, indeed, these early signs of efficacy turn out to validate. But the idea that further combinations of immunotherapies eventually making their way to larger studies and hopefully approval is now well enforced in head and neck cancer. Thank you very much for your attention and hope you enjoyed the ASCO 2019 Annual Meeting.
ASCO: Thank you Dr. Cohen.
Next, Dr. Charles Loprinzi will discuss new research on ways to prevent or treat nausea and vomiting caused by cancer treatment. Dr. Loprinzi is a medical oncologist and the Regis Professor of Breast Cancer Research at the Mayo Clinic. He is also the Cancer.Net Associate Editor for Psychosocial Oncology.
Dr. Loprinzi: Hello, I'm Charles Loprinzi, Regis Professor of Breast Cancer Research at Mayo Clinic. I'm going to be talking today about chemotherapy-induced nausea and vomiting. Now, chemotherapy can cause a lot of nausea and vomiting. That's well known, for years and years, by many people. It's not all types of chemotherapy, but some chemotherapy drugs cause a lot of nausea and vomiting, and others cause little to none. It's not as big a problem now as it was decades ago when we didn't have good drugs to try to prevent nausea and vomiting. Many drugs over the time have been developed for trying to prevent this nausea and vomiting problem. Examples of the drugs that cause a lot of nausea and vomiting are Cisplatinum, and Adriamycin and cyclophosphamide is a combination that is oftentimes used for patients with breast cancer.
So in the past, we have developed many, many drugs for this. Three of the drugs that have commonly been used for the last many, many years for treatment or prevention of nausea and vomiting associated with chemotherapy are corticosteroid medications like Dexamethasone. It's quite cheap. It's got some side effects, but relatively cheap. Then there's a group called 5-HT3 receptor antagonists. I didn't make up that name, but that's the long name for it. They're relatively expensive, some more expensive than other ones. And then there's another group called NK1 receptor antagonists, and they can be quite expensive, sometimes being hundreds of dollars for each dose that's given to try to prevent nausea and vomiting related to chemotherapy.
So a couple years ago, 2016, there was a report in the New England Journal of Medicine, which is a prominent journal for us in the business, that looked at a drug called olanzapine. It's a relatively cheap drug. It's a drug that was developed for psychosis-type problems, given for long term in those patients. But it had been noted that if it's given for just a few days, it seems to markedly improve or decrease the instance of nausea and vomiting, or if people were having nausea and vomiting, it appears actually to help and reverse that particular problem.
So this trial looked at 10 milligrams of this drug for 4 days, given before chemotherapy, and then for 3 more days after that. Patients who were on this study got the 3 drugs that I talked about before with the olanzapine or with the placebo. And it noted that it improved things by quite a bit. The patients who had what we call a complete response, which means no vomiting and no need to take extra medications because of nausea and vomiting, improved from 41% of the patients who were on the placebo, to 64% who were on the olanzapine, a 23% improvement.
And if we looked at a different endpoint there, the number of patients who had no nausea during the five days after chemotherapy, it was 22% in the group that got the placebo and improved to 37% in the group that didn't. So it was a good result in that area. One of the problems with this drug is that it can cause some sedation, cause some drowsiness for some patients. Most patients, not much, but some patients, it's a problem.
So most trials that have been done in the past use this 10-milligram dose. And what we learned at ASCO in 2019, our main meeting that we have once a year, was that people looked at a 5-milligram dose and had looked at 5 milligrams instead of the 10 milligrams. And what it showed is that the results seemed to be quite similar to what was seen with 10 milligrams. They did the study quite the same as what had been reported in the previous trial and the results looks similar. They didn't compare 5 milligrams versus 10 milligrams, which would've been nice because then we would have better information along that line. They did note that there was drowsiness that some patients had, and it looks similar to what was seen with the 10-milligram dose. But these data support, but don't prove, that giving 5 milligrams does look like it's good in this particular setting.
So data from this year also supported that instead of giving the drug during the day when getting the chemotherapy, sometimes, people take it at bedtime, and there, the drowsiness is not as big a problem because you want to be drowsy at bedtime. So it's not proven that it works as well at bedtime, but it suggests that that actually is the case.
Data from this year also supported that if you looked at those 3 drugs I mentioned before and just took out that 1 really, really expensive one, the NK1 receptor antagonist, and put the olanzapine in there instead, that very cheap medication, that that looked like that one with the olanzapine did better than the very expensive one. Not a whole lot better; they looked similar, but a little bit better in that setting, and it was a whole lot cheaper. This was also seen in a publication that came out a couple of years ago which showed the same sort of result. Again, not proof that it's beneficial, that it's okay to do that, but it looked better.
So the next obvious question that comes up then is when you have these 4 drugs that you give, the 3 drugs I mentioned before and this fourth one, what about if you take away that more expensive one and see how they do there? So there was a trial at the ASCO meeting that suggested that the addition of that expensive medications didn't provide a whole lot more benefit. Right now, there is a trial going on across the United States, with about 800 patients who are scheduled to go on this trial, and it's approving about 30 patients a month, which is a pretty good accrual rate, which is looking at this particular question where people would get the 4-drug regimen versus 3 drugs where they take away the expensive intravenous medication.
So, in summary, 35 to 40 years ago, when I started my cancer career, when I was about 10 years old, most patients had a lot a trouble with nausea and vomiting with drugs like Cisplatinum. Now, this a minority of patients who have a lot of problems, and we're continuing to find new things that will make things better along this line. Thank you for your attention.
ASCO: Thank you Dr. Loprinzi.
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