Podcasts about tailorx

Dr. Allison Zibelli and Dr. Megan Kruse discuss the potential benefit of endocrine therapy in ER-low breast cancer; the efficacy and tolerability of triplet therapy in PIK3CA-mutated, HER2-negative locally advanced or metastatic breast cancer; and more key research that will be featured at the 2024 ASCO Annual Meeting.  TRANSCRIPT Dr. Allison Zibelli: Hello, I'm Dr. Allison Zibelli, your guest host of the ASCO Daily News Podcast today. I am an associate professor of medicine and a breast medical oncologist at the Sidney Kimmel Cancer Center of Jefferson Health in Philadelphia. My guest today is Dr. Megan Kruse, a breast medical oncologist and director of breast cancer research at the Cleveland Clinic Taussig Cancer Institute. We'll be discussing key abstracts in breast cancer that will be featured at the 2024 ASCO Annual Meeting.  Our full disclosures are available in the transcript of this episode, and disclosures related to all episodes of the podcast are available at asco.org/DNpod.  Megan, it's great to have you back on the podcast. Dr. Megan Kruse: Thanks, Alison. Happy to be here. Dr. Allison Zibelli: So, let's begin with Abstract 505. This was another analysis of the SWOG S1007 (RxPONDER) trial, which was the trial that was looking at premenopausal women with intermediate risk oncotype scores. And do they benefit from chemotherapy? If you analyze the whole group, they do benefit from chemotherapy, but what this study questions is whether we can pull out the subset of these patients that actually benefit from chemotherapy? And what they tried doing was measuring various endocrine reproductive hormones and found that anti-mullerian hormone over 10 was the only one that predicted for chemotherapy benefit. What are your key takeaways from this study? Will it help us figure out who is truly postmenopausal biochemically? Dr. Megan Kruse: I think this is really promising. This is one of the toughest situations in clinic, honestly, when you have a premenopausal woman who has an intermediate oncotype risk. We know that chemotherapy is not going to make a huge difference potentially in their breast cancer outcomes, but it may add to some small differential benefit. I think that many of our patients are really afraid about leaving any impactful therapy on the table. And so, it'd be nice to have another marker to help sort out who in this group will really benefit. And the AMH levels, I think, are something that are very accessible for most practices, easily orderable. And it seems like this cutoff of 10 is a very well-known cut point in the AMH interpretation, and a pretty clear-cut point. So, I think it gives a little bit more objective view of who may actually benefit or not.  When you look at the results shown in this abstract, for the women in the recurrence score less than 25 receiving chemotherapy followed by endocrine therapy, they had a benefit in five-year invasive disease-free survival of 7.8%. When you look at those oncotype reports and they suggest how much benefit you might get, that's right around the same number you see. So, I think that's supporting that this is the subgroup that's benefiting.  When you look at those patients with AMH less than 10, they actually had a negative 1.7% difference in overall survival. So, you wonder, are we harming these patients by giving them chemotherapy? I think that's too far of a stretch to say. I wouldn't be worried about harm. But hopefully, we can stop giving chemotherapy to patients who truly are not going to benefit if we have an additional biomarker of response. That's what the promise is for this.  So again, another potentially actionable abstract that we can put into practice pretty quickly. It's going to be hard to know how to use this, also in the context of the upcoming OFSET study or BR009, which is of course the study in the same group of premenopausal patients with node-negative or 1-3 lymph nodes involved, and intermediate oncotype scores, randomizing them to endocrine therapy with ovarian suppression versus chemoendocrine therapy. It would be kind of nice to see the AMH levels incorporated into that model to see if the same trend holds true. But I think we go back to the TAILORx and RxPONDER studies many times as good quality data, and the trend here is really striking.  Dr. Allison Zibelli: I really like this study because one of the things I often struggle with in the clinic as a practicing breast oncologist is who's really in menopause. And we end up having these fights with the gynecologists where sometimes our opinions differ. And it would be really nice to have something this clear cut to say, “You're in biochemical menopause or you're not.” So, I look forward to seeing this used in a lot of different ways in the future.  Dr. Megan Kruse: Yeah, I agree. And I think it's based on the other markers we have with estrogen levels, with FSH levels. If you're checking those sequentially in patients, we know they go up and down, and it's really hard to tell what we are capturing at this single point in time. And maybe that's what we're seeing in this analysis is that the AMH is a little bit more stable and reliable marker. So, I really love that. And I don't know about you, but in clinical practice it can be really hard. A lot of our patients have had uterine ablations or hysterectomies but have intact ovaries. And so, figuring out ovarian function status is actually much, much harder than it may seem superficially.  Dr. Allison Zibelli: Okay, so let's focus on Abstract 513. I thought this was really interesting. It's a group of patients that we don't have much data for, and that's women that are ER-low, with an ER of 1% to 10% in early-stage breast cancer. Right now, national guidelines are sort of on the fence about whether these women benefit from endocrine therapy. So that's what this study tried to focus on. How will this study change how we approach this group of patients? Dr. Megan Kruse: This study really gave me pause and made me rethink what I'm doing on a day-to-day basis, because here, what the authors found in a very large NCDB analysis was that for women with ER-low status, so ER 1% to 10% positive, they actually did have benefit receiving endocrine therapy, it seems. What they found, after you adjust for many other confounding factors like age, comorbidity, and PR status, is that patients with ER-low breast cancer when they did not receive endocrine therapy actually had worse overall survival outcomes with a hazard ratio of around 1.2 to 1.3.  This is a group where I have typically not pushed endocrine therapy very strongly. I think the patients, especially now, are receiving such intense therapy with chemoimmunotherapy in the preoperative setting, by the time they reach their adjuvant phase with immunotherapy, maybe with capecitabine, maybe with a PARP inhibitor, endocrine therapy seems, “Oh, why bother after we've done all of this?” And we know that the toxicities of endocrine therapy are real and can be very problematic. And so, I have often felt like it's the least important part of therapy and questioned whether we should even bother. But I think this analysis really challenges that and makes us think twice. And I think it speaks to a theme that we're seeing more and more about the heterogeneity of these breast cancer subtypes. And again, talking about clear-cut points in analysis, nothing is truly black and white. So maybe that little bit of expression does mean something.   It does kind of stand in contrast to what we see in studies of ER-low behaving a bit more triple-negative like, but maybe they're their own category, and maybe it gives us a place to look for other therapy synergy in the future. But it certainly will make me stop and think again when I see a ER 4% patient. Should I talk to them about endocrine therapy?  Dr. Allison Zibelli: Yeah, I totally agree with everything you said there. And we know that this is a biologically different group of patients than the ER strongly positive group, but maybe not as different as we once thought. Dr. Megan Kruse: Yeah. And I think there's still a lot of unknowns here about what if they're ER truly negative and PR a little bit positive. So, these clinical situations don't come up that frequently, but when they do, they're humbling, because I think we really, as much data as we have in breast cancer, it's pretty limited for these types of patients.  Dr. Allison Zibelli: So, let's move on to Abstract 1003, which was a new combination in the INAVO120 trial. It was palbociclib plus fulvestrant with either inavolisib or placebo in patients with PIK3CA-mutated hormone receptor-positive, HER2-negative, locally advanced metastatic breast cancer in the second line, who relapsed within 12 months of adjuvant endocrine therapy completion. This is a big group of patients for us. Can you tell us about the study? And does this triple therapy, in your mind, represent a new standard of care? Dr. Megan Kruse: Yeah, this study was initially presented at our 2023 San Antonio Breast Cancer Symposium, and there I felt like it was a little bit of a surprise. There's been so much talk about PI3K-AKT-PTEN pathway impactful drugs and targetable mutations. We've heard a lot about alpelisib and capivasertib, and how these drugs are fitting into our practice. Then all of a sudden, we have this data with inavolisib that I wasn't really expecting to see. And perhaps I think one of the reasons that this study came about so suddenly, seemingly, and so quickly is because it looks at a really high-risk patient population. And so, these are those patients that are having relapses of their breast cancer within their initial, while on adjuvant AI therapy or within 12 months of stopping. And so, having a marker of this patient group that is developing, I think, early endocrine resistance and it's another space where it's kind of hard to identify who these patients are upfront. And so their response to therapy tends to be one of the best markers of risk moving forward.   So, when this trial was originally presented, what was quite striking is that the progression-free survival was more than doubled for the triplet combination compared to the control arm. And those numbers were PFS of 15 months versus 7.3 months for the triplet versus the control. The response rate was also significantly improved, with the triplet going above 50%, versus a response rate in the control of about 25%. So, the results were really striking. But they clearly come with some caveats, which are that this is a very defined patient population of risk. Of course, they have to have the biomarker of a PIK3CA mutation, and in the control arm here, there was no PIK3-targeted medication. And so you wonder, are we just getting better results by including that more specific targeted therapy earlier on? It's hard to know, but I think that could certainly be a big part of this.  And the other caveat, when I'm looking at the data, is how might we think about this in our real population? Because as we know, drugs that impact this pathway tend to have a lot of toxicity concerns, primarily hyperglycemia, diarrhea, and rash. And with this particular agent, there was also notable stomatitis, which is something we've seen with everolimus, of course, in this pathway, but not maybe as much with alpelisib and capivasertib. When you're thinking about all of those toxicities, keep in mind that this trial population included patients with a pretty tight fasting blood sugar requirement, A1c of less than 8, and not requiring insulin. So all of that being said, I think this combination seems really intriguing for efficacy. This is a patient population I'm worried about, because we know that these patients are likely not going to get the same upfront benefit of CDK4/6 inhibitor-based therapy, like maybe we see for a patient with long disease-free survival or de novo metastatic breast cancer. But I think it's going to have some meaningful issues in clinic regarding tolerability. And then, of course, the regimen is more complex. We're talking about two different oral agents and an intramuscular injection, which could be hard for some patients, and it's going to have some decent financial toxicity associated with it.  So, I think it's really, really exciting and has the potential to make an impact in first-line therapy. But I don't envision it being the standard of care first-line therapy for everyone, particularly in light of some of the other data we have in the first line questioning, like from the SONIA trial, how important is CDK for everyone? Again, this is I think where we're starting to get subsets within subsets of this first-line patient population of who needs escalation of therapy and who may benefit from more de-intensified therapy. Dr. Allison Zibelli: I agree, these agents have significant toxicity, and especially financial toxicity is something that we at the academic setting frequently forget about because a lot of our patients are on trials. So, it will be interesting to figure out how we're going to use these agents in real life.  So, for our final abstract, I wanted to discuss Abstract 10508, which was a prevention trial. I think pretty much everybody's patients are going to be asking them about this because it's about GLP-1 inhibitors. We know that bariatric surgery does prevent obesity-associated cancers. This study explored whether the GLP-1 agonists could offer a similar result to bariatric surgery in patients with BMIs over 35. What do you think about this study?  Dr. Megan Kruse: I thought this was such an interesting and timely study and question. These drugs are out there – Ozempic, Mounjaros, and Wegovy – and our patients ask about them. And I think there has been a lot of interest for years now about the impact of lifestyle factors on cancer incidence, particularly in breast cancer, where we know that obesity does seem to be related to cancer incidence. And with all of our concerns about hormonal exposure and extra weight, extra adipose tissue being a source of potential extra estrogen, this is a really key topic.   Talking about financial toxicity, again, I think that is honestly probably the bigger hurdle because this study does reinforce that patients who are receiving GLP-1 receptor antagonists and those who have had bariatric surgery do benefit in terms of cancer-related survival and all-cause related survival. So, I think the impact on metabolic factors is making a difference in cancer incidence and outcomes. But access and equity will be the big issue here, right? Dr. Allison Zibelli: Yes. Dr. Megan Kruse: Can we get patients on these drugs? I certainly have had patients with a history of breast cancer who have been on these medications, and they have done great with them in terms of weight loss. We know that our therapies, many times, do have the side effect of weight gain. So, I wonder if there is a part of weight management that maybe we haven't talked about so much as oncologists that we need to talk about moving forward and would be very welcome by our patients. But it'll have its own caveats, of course. Not only the financial issue but there's the durability issue. And I think when you look at the degree of impact of these medications versus bariatric surgery, you do see a greater impact from bariatric surgery, in not only the degree of weight loss but also the sustainability of that weight loss. So, I think for the right patient at the right time, bariatric surgery may still be the better option, but that's not going to be an option for a lot of patients. It is a huge shift in lifestyle and medications and many ways might be easier, so more to come.   I also wonder about looking at this data through the lens of different cancer types. What will we find out? Is the trend for colon cancer going to be different from the trend for breast cancer? Will the trend within breast cancer be different for breast cancer subtypes? I would very much welcome more data in this space, and it is nice to see a first step forward. Dr. Allison Zibelli: I thought the most interesting thing about this study was that while bariatric surgery patients lost more weight, GLP-1 patients had a higher decrease in obesity-related cancer risk. So, it shows to me that there is something beyond just weight. It is something in metabolism that is driving these cancers.  Dr. Megan Kruse: Yes, and I think that that goes back to some things we have thought about for a long time with insulin levels and insulin-like growth factor, and all of these things that I think when our patients look at more metabolic approaches to cancer control, this is probably what we are trying to get at. We have just never had great ways to measure it or influence it, and perhaps now we finally do. I would love to see some partnering work here in the future with oncologists and endocrinologists and digging into these patients who have great responses to see what we are actually seeing at the hormone level. Dr. Allison Zibelli: Well, thank you so much, Megan, for your great insights today on the ASCO Daily News Podcast. We really appreciate you coming to talk with us again. Dr. Megan Kruse: Thank you. It has been a great conversation. Thank you for opening my eyes to these abstracts, and I am happy to see what else ASCO brings. Dr. Allison Zibelli: And thank you to our listeners for joining us today. You will find links to all the abstracts we discussed today in the transcript of this episode. Finally, if you value the insights you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. It really helps other people find us. Thank you for listening.   Disclaimer: 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. The guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.   Follow today's speakers: Dr. Allison Zibelli Dr. Megan Kruse @MeganKruseMD   Follow ASCO on social media: @ASCO on Twitter ASCO on Facebook ASCO on LinkedIn   Disclosures: Dr. Allison Zibelli: None Disclosed   Dr. Megan Kruse: Consulting or Advisory Role: Novartis Oncology, Puma Biotechnology, Immunomedics, Eisai, Seattle Genetics, Lilly

The 2022 San Antonio Breast Cancer Symposium featured five days of research presentations, educational sessions, and posters. The amount of research presented can be overwhelming, so we asked Dr. Stephanie Graff to break down the key take-aways for people who've been diagnosed with breast cancer. Listen to the episode to hear Dr. Graff explain: updated results from the monarchE study updated results from the TAILORx study results from the RIGHT Choice trial her thoughts on whether HER2-low breast cancer is a distinct subtype

Dr. Hope Rugo, professor of medicine and director of Breast Oncology and Clinical Trials Education at the University of California, San Francisco Helen Diller Comprehensive Cancer Center, highlights key studies in breast cancer featured at the 2021 ASCO Annual Meeting.   Transcript: ASCO Daily News: Welcome to the ASCO Daily News podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. My guest today is Dr. Hope Rugo. She is a professor of medicine and the director of Breast Oncology and Clinical Trials Education at the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco. Dr. Rugo joins me to discuss key advances in the breast cancer field featured at the 2021 ASCO Annual Meeting. Dr. Rugo has received research support for clinical trials through the University of California from Pfizer, Merck, Novartis, Lilly, Roche, and other organizations. Her full disclosures are available on the transcript of this episode at asco.org/podcasts. Dr. Rugo, it's great to have you on the podcast today. Dr. Hope Rugo: Oh, it's great to be here. ASCO Daily News: There were many interesting studies in breast cancer featured at the Annual Meeting. Thank you for being here to highlight some of them. Let's start with the OlympiA trial. This is LBA1. This remarkable study found that adjuvant olaparib extends disease-free survival in BRCA-mutated early stage HER2-negative breast cancer. What can you tell us about this trial? Dr. Hope Rugo: Well, this is really such an amazing study, in terms of the results and its practice-changing impact. The study actually kind of interestingly was published in the New England Journal [of Medicine] 2 days before it was presented. And even though we had all seen the data, it was really such a, I think, moving presentation in terms of really changing the face of treatment for women and men with BRCA1 and BRCA2 associated breast cancer. Of course, olaparib and talazoparib are both PARP inhibitors that are approved to treat metastatic breast cancer associated with BRCA1 and BRCA2 mutations. And in those randomized trials, they showed improvement in response and progression-free survival, but not clear differences in overall survival. So, of course, when we have an impact in the metastatic setting, the next step is to move into early-stage breast cancer. But that's quite a challenge given the fact that you have to test and find the mutation, which is challenging in some parts of the world. And then you have to decide which group of patients need more than standard therapy. So the OlympiA trial randomly assigned patients who had pathogenic BRCA1 or BRCA2 mutations and HER2-negative, either hormone receptor-positive or triple negative breast cancer, to receive a year of olaparib or a placebo. And the patient eligibility was further defined. If you had triple negative breast cancer, you could have had any residual disease after neoadjuvant therapy, or you had to have a tumor greater than two centimeters or a positive node. If you have hormone receptor-positive disease keeping in mind the benefit of adjuvant endocrine therapy. If you didn't have a pathologic complete response to neoadjuvant therapy, you had to have a few other high-risk features using the CPS plus EG score. And if you received adjuvant therapy, you had to have four or more positive nodes, so stage III disease. All patients had to have received at least six cycles of chemotherapy, radiation as indicated, and of course, hormone therapy was given for hormone receptor-positive disease. There were over 1,800 patients randomly assigned, which was pretty, I think, impressive given the fact that everybody had to be tested. And the whole idea behind the trial is that you would enroll a group of patients who still had a high residual risk of recurrence, even though you got standard and reasonable adjuvant or neoadjuvant therapy. It's important to keep in mind when you think about the results of this trial is that having a BRCA mutation, and in particular BRCA1, increases sensitivity to chemotherapy. So the pathologic complete response rates, for example, in the neoadjuvant setting for triple negative breast cancer with the BRCA1 gene mutation, are higher than in patients who don't have a germline mutation. And so you're really looking at a group of patients who have high-risk disease because they didn't have a pathologic complete response if it was the neoadjuvant setting. Now, of the patient population, a little over 70% had BRCA1 mutations. The rest had BRCA2 mutations. And for the triple negative group, that represented a large portion of the population, about 80%. Again, the rest, a little under 20%, had hormone receptor-positive disease. As you would expect, more than 50%, about 60%, were premenopausal. And about 50% received neoadjuvant therapy. There's always a question about whether or not treatment with prior platinum-based therapy, which is also effective when you have DNA repair deficiency, such as in the germline BRCA mutations, whether or not that would affect sensitivity. A little more than a quarter of the patients had received a platinum chemotherapy agents. And the invasive disease-free survival, the primary endpoint of this trial, was really remarkable. There was an 8.8% improvement in a 3-year invasive disease-free survival rate in patients taking olaparib versus placebo, a very big p-value, and a hazard ratio 0.58. This is really dramatic. The curves separated early, and they remained separated. So that it was the IDFS was 77% for patients on placebo and about 86% in patients who were receiving olaparib, just really very impressive. And one of the things you want to find out about is are you changing the rate of distant recurrence. And indeed, not only were there less distant recurrences, but if you look at distant excluding the brain, that's where you really saw the biggest difference. There was a small difference--hard to know if it really is significant--1.5% less brain recurrence is a big issue for patients, particularly with triple negative disease. It was a little less contralateral invasive disease, but it wasn't anything significant. So really, what you were preventing was the kind of recurrence we don't want to see, which is distant recurrence. And then if you looked at the distant disease-free survival, the absolute improvement for metastatic disease was 7.1%. Again, the curve separated early and stayed separated over time. Now, overall survival, of course, is the golden endpoint that you want to look at. There were numerically less deaths in the olaparib arm, 59 versus 86 in the placebo arm. Most of these deaths were due to breast cancer. And the hazard ratio is 0.68. Although the p-value was 0.024, that didn't meet the statistical plan, which was a p less than 0.01 in terms of how the statistics can be balanced in this trial. But the overall difference was 3.7%. And of course, there were subgroup analyses done, which showed that everybody benefited. It was impossible to see a difference. And again, only a small number of patients relatively receive platinum, so it's hard to know whether or not that changed the response. In terms of the side effects--you always want to think about side effects--it was exactly what you would have expected from what we [expect] in the metastatic setting. Not a lot of grade III or greater toxicities. Mainly anemia was the most common at 9%, and 5% neutropenia, a little bit increase of grade III fatigue, but only 2%. The rest of the toxicities were all grade I and II. And of note, olaparib does cause nausea, 57% of patients versus 23% reported nausea with olaparib versus placebo. But normally, you can manage this nausea and the anemia by actually dose reducing and first holding and then dose reducing. One of the big questions, of course, with PARP inhibitors is if you're inhibiting repair of DNA, are you causing leukemia--new primary cancers? And it was very encouraging. Again, it's 3 years, so we need to be followed a little bit longer, maybe 5, but it was 0.2% or 0.3%. There was no increase in myelodysplasia or myeloleukemias with the use of the PARP inhibitor, which is really important. And the global quality of life scores were identical. So even with these side effects, they could be managed and didn't impact global quality of life. And then in terms of the paper, the additional information the paper gave is that most of the people who required a transfusion received only one transfusion of red blood cells. So I think with the caveat that there are some additional side effects, they are generally able to be managed well. Quality of life is maintained. And there's a huge early difference in the most important endpoints that we look for in these trials--invasive disease-free survival and most importantly, distant disease-free survival. So definitely history in the making. ASCO Daily News: Excellent. Thank you for sharing these fantastic results from the OlympiA trial. The ECOG-ACRIN Research Group presented EA1131, a study of platinum-based chemotherapy or capecitabine in patients with residual triple negative basal-like breast cancer following neoadjuvant chemotherapy (Abstract 605). This interim analysis really highlighted the need for better therapies for this patient population. What are your thoughts on this trial? Dr. Hope Rugo: Well, this, I think, is an important trial. Ingrid Mayer from Vanderbilt designed the trial with ECOG and actually presented the data. There will be a lot more data coming from this study because they collected tumor tissue and are doing a lot of different analyses, which might help us understand the benefits of different treatments in different subgroups of patients with triple negative breast cancer. Now, this trial really focused on patients who have the highest risk disease after neoadjuvant therapy, clinical stage II or III triple negative breast cancer diagnosis. They received the standard neoadjuvant chemotherapy. And they had to have tumors that were greater than one centimeter in the breast at the time of surgery or any positive lymph nodes. So this is actually a group of patients who we already know have a high-risk of distant recurrence. They did do an analysis of the tissue using a PAM50 assay to understand which tumors were basal or non-basal like. And patients were randomly assigned to receive capecitabine by the CREATE-X trial, which showed an improvement in overall survival when capecitabine was given to patients with residual triple negative breast cancer after neoadjuvant chemotherapy in Japan and Korea, versus carboplatin or cisplatin by treating physician discretion (DOI: 10.1056/NEJMoa1612645). The patients received four cycles every 3 weeks of carbo or cisplatin. Now, one thing that's important to keep in mind is in Japan where the CREATE-X trial was designed in Korea where it also participated, the capecitabine dose was the original U.S. Food and Drug Administration (FDA)-approved dose, where it was a little bit higher, 1,200 milligrams per meter squared twice a day, 2 weeks on, 1 week off. In the U.S., patients don't tolerate this very well. And there is a different metabolism in Asian patients, where they can tolerate a higher dose of 5FU and capecitabine with not as much toxicity due to pharmacogenomics. The patients in the ECOG-ACRIN trial received capecitabine at 1,000 milligrams per meter squared twice daily with the same schedule, which is really all that's tolerated. So the objective of this trial was to see whether or not you could do better or the same if you received a platinum versus capecitabine with the idea that DNA damaging agents work very well in basal-like triple negative breast cancer. So the patients were enrolled in this trial. 415 patients were randomly assigned. And then the data safety monitoring group who were following the results at the interim analysis ended up closing the trial because they found that based on the statistics so far that it was unlikely that the platinum arm would either be better or worse than the capecitabine arm. And they saw more toxicity in the platinum arm. So the trial was closed. And that's the data that was presented. So there was a total of 160 patients who received capecitabine, [and] 148 [patients] who received platinum. Most of the patients had basal-like disease. The age, it was about 52. It's all what you would have expected to see in this patient population. So I don't think we have any concerns about the patient population. The 3-year invasive disease-free survival in patients with basal-like triple negative breast cancer, the primary endpoint of the trial, was identical between the two arms. But actually, discouragingly, it wasn't great. So IDFS for capecitabine was 49% and platinum 42%. So this was actually very disappointing data. And I think it just highlights how we really need to provide better treatment for our patients who don't achieve pathologic complete responses to the best neoadjuvant therapy. It is true that the ECOG-ACRIN trial didn't require that patients receive anthracyclines, but 85% did. So I think that we feel really comfortable that they got good chemotherapy. They looked in the non-basal-like sub-type. And in the non-basal-like sub-type, which are cancers that are more likely to be responsive to capecitabine in the metastatic setting, actually, the outcome, although small numbers, looked better with capecitabine than with getting the platinum-type therapy. And if you looked at non-basal versus basal, regardless of therapy, the patients who had non-basal-like disease did much better than the patients who had basal-like disease, something that we would have guessed, but hasn't been shown before. So I think it was really important, [and] really helps us to identify the patients who need the most intervention. But even the basal group, the IDFS, the non-basal group, it was 55.5%. So better than basal at 46%, but still you got 45% of patients with invasive disease-free survival event over a 3-year medium follow-up. Overall survival at 3 years, also, was disappointing at about 66% for capecitabine and 58% for platinum. So I think that, really, this trial just identified, I think, in a very confirming way how we need to make progress in the treatment of these patients who have residual disease after neoadjuvant chemotherapy. In terms of toxicity, the platinum-based therapy clearly was more toxic. Most of the toxicity that was seen was grade I and II, as you would expect, but there was more grade III toxicity even with the platinum-type therapy. Again, as you would expect. You get hand-foot syndrome with capecitabine and not with platinum. But there was more of the standard toxicities that you would expect with the platinum or bone marrow suppression, primarily some thrombocytopenia, et cetera. So when they looked overall at the trial population, I mentioned that most had basal sub-type by PAM50. It was 80%. So it is a group of patients where I think even going into neoadjuvant therapy about 80% have basal-like disease. So I think it makes us very interested in the results that we expect to see in the very near future from the KEYNOTE 522 trial, where we've seen an improvement in pathologic complete response, particularly in patients with node positive disease with the addition of pembrolizumab, to standard taxane platinum and anthracycline-based neoadjuvant chemotherapy (DOI: 10.1056/NEJMoa1910549).  But a very recent press release noted that they have reached their event-free survival endpoint. And that pembrolizumab improves event-free survival. And the importance of this data, which, of course, has not yet been shared, so we have to see what it looks like and what the differences are, is that they had shown earlier at the FDA's ODAC meeting in February of this year that possibly patients who don't achieve a PCR, who received pembrolizumab before and after surgery, had a better outcome than patients who did not receive pembrolizumab and received placebo. So how we incorporate capecitabine into the post-neoadjuvant treatment or other novel agents will very much be a subject of the next few years as we sort this out. But if the pembrolizumab data is indeed exciting--and we'll talk more about the durvalumab data in just a moment--then I think the question would be, what chemotherapy do you give? And based on this trial, there is absolutely no indication for platinum postoperatively in patients with residual disease after neoadjuvant therapy. Capecitabine should be given. But clearly, we need better options for therapy. And this is also being studied with some of the new antibody drug conjugates, like sacituzumab govitecan to see whether or not we can improve outcome in these patients. ASCO Daily News: Right. Well, let's look at Abstract 506. This is the phase II GeparNuevo study. The data presented by the German Breast Group showed that neoadjuvant durvalumab improves long-term outcomes for patients with triple negative breast cancer. What is your takeaway from this study? Dr. Hope Rugo: You know, this was really interesting, and I think unexpected results based on their original presentation. This was a phase II neoadjuvant trial in patients with triple negative breast cancer. And the data by the GBG and Sibylle Loibl, who runs the GBG, had already presented the data from the primary endpoint of this smaller neoadjuvant trial, which was pathologic complete response. And what they did in this trial was they treated patients with a nab-paclitaxel followed by epirubicin and cyclophosphamide. And the patients were randomly assigned to receive the checkpoint inhibitor durvalumab versus placebo. There were 174 patients stratified by a low, medium, or high TILs. And their main endpoint, as I mentioned, was PCR. So this is a secondary endpoint of invasive disease-free survival. A group of patients received 2 weeks of durvalumab as sort of a lead-in first. And they've looked at that group separately. But it's hard to know because it's such a small trial what that means. And nobody is using a lead-in right at the moment. So their primary endpoint, as I mentioned, has been published already in Annals of Oncology in 2019 (DOI: 10.1093/annonc/mdz158). Although numerically there was a higher PCR rate in the durvalumab treated arm, this was not statistically significant. The p-value is in no way significant. And they looked at, in a forest plot, they showed that the patients who had the window seemed to have a higher PCR, but it was hard to justify exactly why that was the case in this group of patients. Now, it's important to keep in mind that the data that we have from KEYNOTE 522, the neoadjuvant trial with pembrolizumab, and IMpassion 31, the trial with the atezolizumab, showed the benefit, particularly in patients with node-positive disease. In this trial, about a third of the patients had stage zero or I breast cancer. So 61 out of the total of 174 patients did not have positive nodes. So we thought the PCR difference really wasn't seen because they had a low-risk population. But now, they're presenting their secondary endpoint of invasive disease-free survival in this group of patients. And what they saw, actually, at a median follow-up of about 44 months, they saw a 12 IDFS events in the durvalumab arm and 22 in the placebo arm. And actually, there were twice as many distant recurrences in the patients treated with placebo versus durvalumab. So 13 versus six events for distant recurrence. So I think that's actually a really important endpoint. And if you looked at the invasive disease-free survival at 3 years, it was 77% for placebo and almost 86%. So almost a 9% difference in favoring the patients who received durvalumab. Pretty dramatic, you know? A hazard ratio of 0.48. And they did have a p-value of 0.0398. So that was quite interesting. And they looked at distant disease-free survival. Numbers are small here, but I think it's a really important endpoint, and overall survival. Overall survival is early to see, but they could see--this is a long follow-up, but it's a small study rather than early--and they showed that overall survival difference was 83.5% in the placebo arm and 95.2% in the durvalumab arm. Again, secondary endpoints with a hazard ratio is 0.24 and, again, a p-value of 0.1. Distant disease-free survival, such an important endpoint, was a huge difference 78.4% versus 91.7%. Again, hazard ratio of 0.31. So pretty dramatic. And when you looked at subgroups of patients, and they looked at PD-L1 positive versus negative. Almost all of the patients had PD-L1 positive disease, so 138 versus 20 that were PD-L1 negative. So it's kind of hard to interpret any of that. And that trial was stratified by stromal TILs anyway. They did show that patients who had a PCR had a better outcome than patients who did not have a PCR. But among the patients who had a PCR, the patients who had durvalumab did better, again, with almost a 10% difference, favoring durvalumab versus placebo. Now, this is a phase II randomized trial, so it's small. And so this is really hypothesis generating. But given the fact that KEYNOTE 522 and IMpassion 31 (NCT03197935) gave the checkpoint inhibitor for a year, and in this situation patients received durvalumab only in the neoadjuvant setting, it suggests that they saw this impact in patients who had a PCR that was greater in patients receiving durvalumab placebo. So it suggests that even though the PCR improvement was not significant, that just the treatment with a checkpoint inhibitor changes long-term outcome. And we know that there's more toxicity by giving longer course checkpoint inhibitor therapy, so we expect that we might see approval of pembrolizumab based on the KEYNOTE 522 trial. And it will bring up the question of whether or not you need a whole year of treatment to improve outcome. And whether or not simply treatment preoperatively might be sufficient, particularly in the patient group who achieves a PCR. It will be, I think, very, very important to be able to evaluate this in order to reduce the toxicity, both the physical toxicity, as well as financial toxicity from use of checkpoint inhibitors in patients with triple negative breast cancer. Also, we know that a third of these patients had stage I disease. And I think we really need to look at the larger trials quite carefully to understand whether or not all patients need checkpoint inhibitors who have triple negative disease. Or whether or not we could more correctly focus on the patients who have higher risk disease, node-positive disease who've been shown to have less tumor infiltrating lymphocytes than patients who have less burdensome disease at diagnosis. ASCO Daily News: Right. So what about the subset analysis in Abstract 1011 that looked at outcomes in patients who are age 65 and older in the phase III ASCENT study of sacituzumab in metastatic triple negative breast cancer? Can you tell us about ASCENT and the toxicities associated with this antibody drug conjugate in this older patient population? Dr. Hope Rugo: Well, ASCENT, of course, is a practice-changing trial as well. It led to the final formal approval of sacituzumab govitecan for patients with metastatic triple negative breast cancer in the second line or greater earlier this year after accelerated approval was granted earlier in 2020. This antibody drug conjugate is given 2 weeks on, 1 week off. And the primary toxicity is neutropenia, and then to a lesser degree diarrhea. But overall, the drug is quite well-tolerated. In the overall parent ASCENT trial, as the listeners know, showed an improvement in progression-free and overall survival at the first analysis. Very impressive data with sacituzumab in these heavily pretreated triple negative breast cancer population, compared to treatment of physician choice with standard chemotherapy options, where about 50% of the patients received eribulin, which had already been shown to be better in terms of overall survival compared to other chemotherapy in the subset of patients treated in the past with eribulin who had triple negative disease. So at ASCO this year, Kevin Kalinsky presented on behalf of our authorship group a subset analysis looking at patients who were age 65 and older to better understand whether there was more toxicity and as much benefit in this group of patients. So important when we're looking at novel therapies. So overall, there were 44 patients treated with sacituzumab and 46 with treatment of physician choice who were age 65 or older. Most of the patients had received two to three lines of therapy. And about 40% had received greater than three lines of therapy. The median prior anticancer regimen was pretty similar to the overall group. Most of the patients had initially been diagnosed with triple negative disease, but really, interestingly, about a third of the patients had ER-positive or something else disease initially and were triple negative on biopsy in the metastatic setting. So an interesting subgroup of patients that were also looked at separately and appeared to benefit to the same degree as the triple negative patients. So we looked at progression-free survival in this group of patients looking at patients under age 65 and age 65 and older. A hazard ratio was even greater in the age 65 or older for--it's hard. These are subset comparisons, but the hazard ratio is 0.22 going from 2.4 months with standard therapy to 7.1 months with sacituzumab. The hazard ratio in the younger group was 0.46. But still a big difference in progression-free survival. And then in terms of overall survival in the age 65 and older group, it went from 8.2 to 15.3 months with a hazard ratio of 0.37. And so also really quite dramatic. And overall response was also significantly increased with, in fact, the only responses seen in the age 65 or older group seen in the sacituzumab group. There were no complete or partial responses in the treatment of physician choice group. Of course, really important to look at safety in our older patients because we know that generally there is more toxicity in that group of patients. But actually looking at grade III or greater toxicity, keeping in mind it was 49 [patients] in the older group versus 209 patients in the younger group, there was no difference in grade III or greater toxicities. There were more dose reductions. So 35% reduced their dose versus 19% older versus younger. But there was no difference in adverse events that led to discontinuation between the younger and older group. So that was really encouraging. We see this in almost all trials that older patients have more dose reductions and that was seen here as well. And we also looked at this very small subset of patients who are age 75 or older versus age 65 or older. And the rates of adverse events were similar, albeit smaller number of patients. There was, if you looked at specific treatment-related adverse events that led to dose reduction, it was a neutropenia, fatigue, diarrhea, febrile neutropenia in a small number, 6% versus zero in the treatment of physician choice and nausea. So it's helpful to know what those toxicities are when you're thinking about treating these patients in clinical practice. And in a patient who might be a little less strong, a little older, more comorbidities, so slightly more frail, I would consider starting potentially at a 3/4 of the dose and then going up if they tolerate it well, versus starting at the full dose and getting a lot of toxicity. But this was really encouraging data that showed that you can give the drug to patients who are older and even elderly at age 75 or greater. So that was good to see. And then Lisa Carey presented additional data looking at patients who were treated in the second line or greater because the formal approval by the FDA is in second or greater line. But most of the data looked at patients who were treated in the third or greater line. So you were supposed to have at least two chemotherapies for advanced disease, but you could have had one in the early stage setting if your progression occurred within 12 months. So there were 33 and 32 patients in the sacituzumab and treatment of physician arm, respectively, who had a recurrence within 12 months of neo or adjuvant chemotherapy. They got one line of chemotherapy in the metastatic setting. And then they were randomly assigned on the ASCENT trial. And as you would expect, tiny numbers, right? 33 and 32 patients. But you get a lot of events in this patient population. The PFS was much greater in patients getting sacituzumab than treatment of physician choice. Hazard ratio of 0.41. And also, if you looked at overall survival, it was double. The hazard ratio is 0.51, even in the second line setting. I think it's really interesting to look to see what the toxicity is relative to the lines of therapy. But because the numbers are so small, it's really hard to look at this now. We'll see more data on toxicity when we see data in the first line, as well as the post-neoadjuvant setting in ongoing trials. And I think that will help us a lot to understand what I think we see in the current clinical trials and in practice, which is that patients who are treated in this second line setting have less hematologic toxicity as well as GI toxicity and need less growth factor intervention, et cetera. And I expect that we'll see that in the post-neoadjuvant setting as well. These numbers are too small to really look at any differences in toxicity. But all of this data I think was incredibly encouraging for us in terms of the use of sacituzumab in patients with metastatic triple negative disease, as well as the expansion to the first line and to post-neoadjuvant setting. ASCO Daily News: Excellent. Investigators of the phase III MINDACT trial, that's Abstract 500, evaluated the survival of patients with an ultra low risk 70 gene signature. How will MINDACT inform clinical practice? And do you think this study might guide more appropriate choices of chemotherapy in women with node-negative or one to three node-positive disease? Dr. Hope Rugo: Well, how MINDACT will inform clinical practice is a very big question. And it already has informed clinical practice identifying patients who are better candidates for chemotherapy and endocrine therapy versus endocrine therapy alone who have stage I and II hormone receptor-positive early stage breast cancer based on their primary outcome results. This particular analysis was something different. So we think about using this 70 gene score and the recurrence score from the TAILORx trial (DOI: 10.1056/NEJMoa1804710) and RxPONDER to try and identify which patients need more therapy versus less therapy. Now, we also know that these scores have some prognostic impact. Clinically, we mainly have used them to decide who should get chemotherapy in addition to endocrine therapy. This trial looked at a different way to use a gene expression scoring system. It's really to identify which patients need less. Given the fact that your middle of the line therapy is endocrine therapy, which patients do we know who will do very, very well with any endocrine therapy and don't need extended duration endocrine therapy? That's really the question here. So they looked at the patients who were in the MINDACT trial and used data published by my colleague, Laura Esserman who looked at a cohort of patients retrospectively and found that patients who had an ultra low score in MINDACT. And that's a score greater than 0.355 where plus 1 is the lowest end of low risk, and minus 1 is the highest end of high-risk, so greater than 0.355. She identified a group of patients who did well, regardless of whether they received tamoxifen or not apparently in this retrospective long-term outcome where there was 15-year follow-up. So they use that data to go into the MINDACT population and to try and understand which patients benefit. And the MINDACT is a much higher risk group of patients. So if you looked at that original trial that Laura Esserman published, these patients had screen detected cancers. And in fact, the 70 gene signature low and ultra low-risk tumors are, as you would expect, over-represented in screen detected cancers. So you've got this excellent survival regardless of treatment. So how did they apply to MINDACT? So in MINDACT, patients were randomly assigned, of course, who had clinical low, genomic high, or clinical high genomic low to receive chemotherapy or not. In this situation, you're really looking at the patients who have genomic ultra low disease. So most of those patients would not be getting chemotherapy because they would already have ultra low disease. So what they found actually when they looked at the overall population of MINDACT, 6,700 or so patients, they found 15% of patients or 1,000 patients fell into this ultra low category. And if then you looked at the patients who were high-risk, it was 36%. And patients who fell into the big low-risk group, it was about 49%, so about half of the population of patients. So they looked at the different metastasis-free interval rates in patients who had genomic low and ultra low-risk disease, regardless of the treatment the patients receive. They all receive endocrine therapy, remember? So they actually found that in patients who were ultra low versus low-risk, that the hazard ratio is 0.65, showing that patients who had ultra low-risk--remember, this was 1,000 patients at 8 years--there was only 36 events. So they had a 97% 8-year distant metastasis-free interval, compared to 94.5% for low-risk and 89.2 in high-risk disease. They looked at breast cancer-specific survival rates as well. And for ultra low-risk in 1,000 patients, there were exactly eight events. 99.6% 8-year breast cancer-specific survival. So really, quite remarkable. So clinical high-risk tumors tend to have larger size, higher grade, be node-positive. We already know that. For the 1,000 genomic ultra low-risk patients, about almost 70% were greater than 50 years. 80% were node negative. 81% had tumors that were T1, so up to two centimeters. And most of them, except for 4%, were grade I and II. 97% were hormone receptor-positive HER2-negative. Only 14% of patients who had ultra low-risk disease received chemotherapy in MINDACT. And most of the rest received endocrine therapy. Some actually didn't receive endocrine therapy. 16% had no adjuvant systemic treatment at all. So if you looked at the genomic ultra low-risk patients and divided them into clinical low-risk and clinical high-risk, there was really no difference in the events overall, a little bit less 8-year distant metastases-free survival, but not much of a difference. So really, a quite remarkable outcome. Now, what you want to know, of course, then is, does it make a difference if you get endocrine therapy at all? And they looked at the patients who had chemotherapy versus no chemotherapy. And as you would expect, it made no difference. Again, it was a tiny number of patients. But if you looked at endocrine therapy versus no endocrine therapy, it was hard to tell. Because, again, no adjuvant systemic therapy was only 157 patients. There were four events. And for the patients, 685 patients who got endocrine therapy, there were 23 events. So the 8-year metastasis-free interval was identical, but there just aren't enough patients in that no adjuvant systemic therapy group to really understand. So what we know is ultra low-risk defines a group of patients who have excellent outcomes. Does it tell us that they don't need adjuvant systemic therapy? No. Eight years really isn't enough time, unfortunately, in is group because 50% of recurrences occur after five years and out to 20 plus years. We have to keep in mind the Early Breast Cancer Trials Group data showing how many recurrences occurred after five years of endocrine therapy. But in this group of patients who have ultra low-risk disease, they clearly do not benefit from chemotherapy. And I think that's regardless of their clinical risk. And it's likely that 5 years of adjuvant endocrine therapy is absolutely all those patients would ever need. If you have a small cancer that's ultra low-risk, could you get by with less than 5 years of endocrine therapy in a patient with a lot of toxicity? Potentially. And I think that's a really important bit of information to take back into clinical practice when you're talking to patients about the duration of endocrine therapy. But a stage I tumor or stage II with ultra low-risk disease, in general, I would treat for 5 years. I think it's important to keep in mind that premenopausal women, even with ultra low-risk stage II disease, have an ongoing risk of recurrence. And I still think that those patients should be treated with a varying function suppression and aromatase inhibitor if tolerated and tamoxifen otherwise because our very young patients tend to have higher risk of recurrence over time. And it's very hard to separate them out in these studies. Interestingly, there are a few young women who have ultra low-risk disease. So I think this really helps us understand yet another impact of genomic tests, which is who needs less therapy, not just who needs more. ASCO Daily News: Great. That's good to hear. Well, finally, the theme of the Annual Meeting was equity. And in Abstract 1092, you and your colleagues at University of California, San Francisco (UCSF) looked at decreased enrollment of patients with advanced lobular breast cancer compared to ductal breast cancer in interventional clinical trials. Can you tell us about this study? Dr. Hope Rugo: Yes, this was a really interesting evaluation. My colleague surgeon Rita Mukhtar at UCSF actually led this evaluation with a very good student who's working with us on some of our research trials. And the idea was that we had observed anecdotally, as have others, that patients with invasive lobular cancer tend to be less likely to meet criteria for clinical trials. So they don't have measurable disease as much. We tend to see sclerotic bone lesions, diffuse infiltration without measurable disease. And it can be much, much more difficult to meet the criteria for clinical trials. So actually, what my colleagues did in this trial is look at whether or not patients with lobular breast cancer are underrepresented in clinical trials. And so they looked at the proportion of interventional stage IV clinical trials that used RECIST in clinicaltrials.gov. And then actually looked at the patients who have RECIST measurable disease who have lobular cancer. And it's really interesting. I mean, we just have a lot less RECIST measurable disease. And in the UCSF cancer registry, patients who were enrolled in clinical trials, if you looked at invasive lobular cancer were markedly decreased if you compare it to patients with other sub-types of breast cancer. So we think that that's probably due to the requirement for measurable disease. And that what we should do in patients who have metastatic lobular cancer is develop trials that are specifically for lobular cancer that focus on the unique biology. And there's a lot of work going on now looking at that biology. And allow patients to enroll based on their disease control rates rather than response. So that we don't require RECIST measurable disease since that's hard to come by in invasive lobular cancer. So I think it's a really important area. It's about 15% of invasive breast cancers. We see a lot of lobular cancer in the metastatic setting. And I think it's unfortunate not to be able to enroll these patients in clinical trials. There is a lot of interest in the cooperative groups in the United States in Europe and in Asia, of course, in trying to do trials that are focused on addressing the needs of patients with lobular cancer, both in the early and late-stage setting. ASCO Daily News: Excellent. Thank you, Dr. Rugo. It's been great to have you on the podcast today. Thanks so much for sharing your valuable insight with us on the ASCO Daily News podcast. Dr. Hope Rugo: It was really a pleasure to participate and thank you for putting together these podcasts. ASCO Daily News: And thank you to our listeners for your time today. If you enjoyed this episode, please take a moment to rate and review us, wherever you get your podcasts.     Disclosures: Dr. Hope Rugo Honoraria: Puma Biotechnology, Mylan and Samsung Research Funding (Institution): Pfizer, Merck, Novartis, Lilly, Roche, Odonate, Daiichi, Seattle Genetics, Macrogenics, Sermonix, Boehringer Ingelheim, Polyphor, Astra Zeneca and Immunomedics. Travel, Accommodations, Expenses: Pfizer, Novartis, Mylan, AstraZeneca, Merck Disclaimer: 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.

First up we discuss RxPonder and what it adds to adjuvant treatment of breast cancer in the context of TailoRx. Then we discuss a recent study (https://jamanetwork.com/journals/jama/fullarticle/2774295)of additional capecitabine following adjuvant chemo in TNBC and what it adds in the context of CREATE-X.

HOPA Now is the official podcast of the Hematology/Oncology/Pharmacy Association, an organization dedicated to supporting pharmacy practitioners and promoting the advancement of Hematology/Oncology/Pharmacy to optimize the care of individuals impacted by cancer.   These educational podcasts are part of our BCOP Preparatory and Recertification Course, which is designed to prepare oncology pharmacists preparing to sit for the BCOP Certification Exam, as well as meet the BPS requirement to complete a BCOP Preparatory/Recertification Review Course.   In this episode of HOPA Now, Dr. Neelam Patel highlights various drug regimens and recommendations including adjuvant Anti-HER2 therapy, PIK3CA, characteristics of CDK4/6 inhibitors, and considerations for adjuvant chemotherapy. She details the key role that pharmacists can play in helping manage potential toxicities and ends with recommendations on when to stop therapy and how to employ supported care.   In this episode you will learn:   Breast Cancer Top 10 Clinical Pearls Utilizing adjuvant Anti-HER2 therapy based on residual disease versus no residual disease The relationship between PIK3CA and the place of Alpelisib in therapy Mechanical characteristics of CDK4/6 inhibitors, dosing recommendations, recent changes, and its place in therapy NCCN guidelines for using endocrine therapy versus cytotoxic therapy in metastatic breast cancer Adjuvant chemotherapy for hormone receptor-positive HER2-negative C and findings of the TAILORx study PARP inhibitors used in treating breast cancers and adjuvant Capecitabine Bone modifying therapy and drug dosing recommendations The evaluation of metastatic disease, when to stop therapy, and supported care   Mentioned in This Episode: HOPA   Quotes:   “Ado-trastuzumab emtansine is recommended in the adjuvant setting if patients have residual disease following neoadjuvant HER2 targeted therapy.” — Dr. Neelam Patel   “Close monitoring and management is one of the key roles that we can play as pharmacists in helping manage these toxicities.” — Dr. Neelam Patel   “If a patient is symptomatic and requires quick disease control, cytotoxic chemotherapy may be recommended.” — Dr. Neelam Patel   “In general, chemotherapy is chosen based on patient-specific risk factors.” — Dr. Neelam Patel  

A disfunção cognitiva em pacientes expostos a tratamentos contra o câncer tem sido cada vez mais observada por meio de testes neuropsicológicos e confirmadas em estudos de neuroimagem, que documentam alterações na estrutura e na função do cérebro. A maioria das pesquisas está concentrada em avaliar o comprometimento cognitivo relacionado à quimioterapia, que possui toxicidade mais aguda e aparente. No entanto, existe um notável interesse entre os pesquisadores em avaliar também a disfunção cognitiva relacionada ao tratamento endócrino, que vem ganhando mais espaço, principalmente em mulheres com câncer de mama localizado. Nesse contexto, no dia 9 de abril de 2020 foi publicado no Journal of Clinical Oncology um importante estudo que avaliou o comprometimento cognitivo em mulheres com câncer de mama localizado recrutadas no estudo TAILORx para receber quimioterapia em associação com terapia endócrina versus terapia endócrina isolada. Foram avaliadas 552 mulheres com recurrence score entre 11-25 selecionadas para responder um questionário funcional de cognição relacionado ao câncer aplicado antes do tratamento, aos 3, 6, 12, 24 e 36 meses. Para falar sobre o desenho e os resultados desse importante estudo, recebemos neste episódio a Dra. Debora Gagliato, oncologista clínica da BP – A Beneficência Portuguesa de São Paulo. J Clin Oncol Epub ahead of print Apr 9, 2020

A special video supplement to a CME conference held during the 2019 San Antonio Breast Cancer Symposium featuring expert comments on the management of ER-positive breast cancer. Featuring perspectives from Dr Harold J Burstein. Use of genomic classifiers to inform therapeutic decision-making for ER-positive localized breast cancer (00:00) Prognostic and/or predictive utility of the various genomic assays for patients with node-negative and node-positive early breast cancer (03:23) Implications of the TAILORx intermediate-risk cohort results for adjuvant treatment for pre- and postmenopausal patients with localized breast cancer (05:27) Effects of prolonging adjuvant aromatase inhibitor therapy beyond 5 years on recurrence and cause-specific mortality (10:42) NSABP-B-42: Ten-year results of extended adjuvant endocrine therapy with letrozole for postmenopausal women with ER-positive breast cancer who have completed previous adjuvant therapy with an aromatase inhibitor (AI) (12:28) Optimizing the use of CDK4/6 inhibitors in the management of ER-positive metastatic breast cancer (mBC); overall survival findings and mechanisms of resistance (14:56) Management of de novo ER-positive, HER2-negative mBC (18:22) Choice of endocrine therapy partner for patients with de novo ER-positive, HER2-negative mBC (21:39) Approach for patients with mBC and disease progression on an AI (24:04) Selection and sequencing of CDK4/6 inhibitors in mBC; comparison of side-effect profiles (26:40) Incidence, identification and prognostic significance of PI3K mutations in patients with ER-positive mBC (31:35) Results of the Phase III SOLAR-1 trial evaluating alpelisib/fulvestrant versus fulvestrant alone for patients with ER-positive, HER2-negative advanced BC with or without a PIK3CA mutation after disease progression on first-line endocrine therapy; FDA approval for breast cancer with a PIK3CA mutation and current clinical role (33:27) Spectrum, frequency and severity of toxicities observed with alpelisib (36:09) Clinical experience with everolimus in mBC; potential for its use after disease progression on a CDK4/6 inhibitor (39:07) Biologic rationale for evaluation of the Bcl-2 inhibitor venetoclax in ER-positive mBC (40:54) Overview of the novel HER2-directed agents trastuzumab deruxtecan and tucatinib for HER2-positive mBC (44:00) Dual targeted approach for patients with ER/PR-positive, HER2-positive mBC (46:40) Investigation of other strategies designed to exploit the PI3K/AKT/mTOR pathway (50:06) Early activity and safety data with the use of CDK4/6 inhibitors as neoadjuvant therapy; ongoing evaluation and potential clinical role (51:08) Perspectives of Dr Burstein and Dr Love on the passing and legacy of the breast cancer revolutionary Dr Bernard Fisher (56:40) Advances in the adjuvant treatment of HER2-positive and triple-negative breast cancer (1:02:24) CME information and select publications

El Dr. Vicente Valero, Presidente Adjunto del Departamento de Oncología Médica de Cáncer de Mama en la División de Medicina del Cáncer, en el MD Anderson Cancer Center de la Universidad de Texas, y profesor del Departamento de Oncología Médica de Mama, de la División de Medicina del Cáncer, en la misma institución, nos comenta brevemente sobre el desarrollo de las plataformas genómicas en cáncer de mama, concretamente sobre los hallazgos del mayor estudio aleatorizado en cáncer de mama adyuvante realizado hasta la fecha, el estudio TAILORx.

We have a variety of topics for you this week! We tackle red light therapy, polatuzumab olatuzumab vedotin in relapsed or refractory diffuse large b-cell lymphoma; we have a hematology/oncology question of the week from Dr. Emerson Chen of OHSU; and we sit down with Dr. Ali Khaki of the Fred Hutchinson Cancer Research Center to discuss his recent paper critiquing TAILORx. Pola for DLBCL: doi.org/10.1200/JCO.19.00172 Financial COI on Twitter: doi.org/10.1001/jamainternmed.2016.8467 Ignoring Valuable Data: doi.org/10.6004/jnccn.2019.7363 Back us on Patreon! www.patreon.com/plenarysession

Breast Cancer Update for Surgeons, Issue 1, 2019 — Part #1: Our interview with Dr Geyer highlights the following topics as well as cases from his practice: Case: A premenopausal woman in her mid-40s with Grade II, ER/PR-positive, HER2-negative lobular breast cancer, a 21-gene assay Recurrence Score (RS) of 10 and a deleterious CHEK2 mutation undergoes a bilateral mastectomy (00:00) Impact of gene-expression assay results on therapeutic decision-making  (04:54) Results of the Phase III TAILORx trial evaluating chemoendocrine therapy versus endocrine therapy alone for patients with ER-positive, HER2-negative, node-negative breast cancer and an intermediate RS (07:00) Clinical utility of the 21-gene and 70-gene assays (12:29) Benefit with the addition of ovarian function suppression to endocrine therapy for premenopausal women with ER-positive breast cancer at high risk for recurrence (14:11) Approach to assessing the adequacy of ovarian function suppression in premenopausal patients receiving aromatase inhibition (17:01) Significance of clinical risk category in prognosis and in the prediction of chemotherapy benefit by age and RS in the TAILORx trial (19:04) Use of adjuvant bone-modifying agents to reduce the risk of aromatase inhibitor-associated bone loss and fracture (24:51) Role of the 21-gene assay RS in guiding neoadjuvant therapy decision-making for ER-positive, HER2-negative localized breast cancer (27:39) Mechanism of action, efficacy and tolerability of CDK4/6 inhibitors for ER-positive, HER2-negative metastatic breast cancer (31:33) Investigation of CDK4/6 inhibitors alone or in combination with endocrine therapy in the neoadjuvant and adjuvant settings (36:00) Case: A postmenopausal woman in her mid-50s with Grade I, ER-positive, PR-negative, HER2-negative infiltrating ductal carcinoma (IDC) with 1 positive node and a RS of 20 receives an aromatase inhibitor and denosumab (39:49) Approach to the selection of adjuvant endocrine therapy; management of aromatase inhibitor-associated arthralgias (43:33) Clinical and genomic risk to guide the use of adjuvant therapy for breast cancer (46:22) Prospective data with and ongoing evaluation of the 21-gene and 70-gene assays for patients with node-positive disease (49:23) Results from the Phase III KATHERINE study evaluating adjuvant T-DM1 versus trastuzumab for patients with HER2-positive localized breast cancer and residual disease after neoadjuvant treatment (54:20) Rationale for the design and entry criteria of the KATHERINE study (58:18) Mechanism of action, activity and tolerability of antibody-drug conjugates (1:02:46) Second opinion: Therapeutic options for a patient in her mid-40s with recurrent, locally advanced, ER/PR-positive, HER2-positive breast cancer (1:06:23) Clinical implications of the KATHERINE trial results (1:14:53) CME information and select publications  

Breast Cancer Update for Surgeons, Issue 1, 2019 — Part #2: Our interview with Dr King highlights the following topics as well as cases from her practice: Recent developments in the surgical care of patients with breast cancer (00:0s Predictive versus prognostic role of the 21-gene assay RS in ER-positive, HER2-negative, node-positive breast cancer (01:45) Clinical implications of the TAILORx trial results (05:11) Reliability of the 21-gene assay RS in guiding neoadjuvant therapy decision-making (07:19) Impact of genomic assay testing and clinical features on the use of chemotherapy after the implementation of standardized reflex testing criteria  (10:39) Clinical utility of the 21-gene assay RS in the selection of therapy  (15:34) Application and utility of the MINDACT trial results; use of the 70-gene signature assay in breast cancer  (17:48) Criteria for surgeon-initiated reflex gene-expression profile testing for patients with early-stage breast cancer to reduce delays in the initiation of chemotherapy  (19:26) Surgeon variability and factors predicting the need for reoperation after breast-conserving surgery (24:22) Recent trends in reoperation after initial lumpectomy for patients with breast cancer (26:45) Multidisciplinary management of the axilla for patients with breast cancer undergoing primary mastectomy (28:25) Optimal locoregional management of sentinel node-negative and node-positive breast cancer (31:54) Key issues regarding gross and microscopic evaluation of breast and lymph node specimens after neoadjuvant systemic therapy (36:36) Importance of accurate specimen evaluation in assessing treatment response (39:15) Factors predicting the use of preoperative therapy for young women with breast cancer; impact on breast-conserving surgery (41:55) Updated AJCC Staging Manual: Incorporation of tumor biology into breast cancer staging to tailor treatment and refine prognosis (43:46) Case: A woman in her mid-40s with ER/PR-negative, HER2-positive IDC receives neoadjuvant paclitaxel/trastuzumab/pertuzumab on the Phase I DAPHNe trial (47:22) Perspective on the results of the KATHERINE trial (52:52) Threshold for neoadjuvant therapy in triple-negative versus HER2-positive breast cancer; side-effect profile of paclitaxel in combination with trastuzumab and pertuzumab (54:51) Case: A woman in her mid-30s with triple-negative breast cancer has residual invasive disease in the breast and axillary lymph nodes after receiving neoadjuvant dose-dense AC followed by paclitaxel (56:49) Perspective on the importance of genomic testing in guiding treatment decision-making for patients with newly diagnosed disease (1:01:7s Surgical treatment options for patients with triple-negative breast cancer and germline BRCA mutations (1:03:20) Case: A woman in her mid-40s with ER/PR-positive, HER2-negative IDC receives a RS of 18 (1:05:37) Effects of age, menopausal status and RS on the prediction of benefit from chemotherapy (1:08:14) CME information and select publications  

Breast Cancer Update, Issue 3, 2019 — Part 1: Our interview with Dr Goetz highlights the following topics as well as cases from his practice: Case: A woman in her mid-30s with de novo ER-positive, HER2-negative metastatic breast cancer (mBC) achieves a complete clinical response to palbociclib, letrozole and ovarian suppression (00:00) Importance of providing support to patients and their families coping with a diagnosis of mBC (01:15) Therapeutic options for patients with de novo ER-positive, HER2-negative mBC (03:45) Activity and tolerability of gonadotropin-releasing hormone agonists (05:35) Selection of patients for treatment with CDK4/6 inhibitors in combination with endocrine therapy (09:07) Mechanism of action of CDK4/6 inhibitors (12:13) Role of everolimus and alpelisib in the management of ER-positive mBC (14:30) Implications of ESR1 mutations for the management of ER-positive mBC; use of selective estrogen receptor degraders (SERDs) (16:15) Activity of the selective estrogen receptor modulators endoxifen and lasofoxifene for mBC with ESR1 mutation (19:48) Tolerability profiles of the CDK4/6 inhibitors palbociclib, ribociclib and abemaciclib; dose reduction to mitigate side effects (21:21) CNS penetration of abemaciclib; management of abemaciclib-associated diarrhea (25:26) Effects of site and extent of metastases on outcomes with CDK4/6 inhibitors (27:02) Efficacy of CDK4/6 inhibitors in combination with endocrine therapy for ER-positive mBC (29:29) Survival outcomes with CDK4/6 inhibitors and endocrine therapy for ER-positive mBC (31:28) Response to palbociclib and endocrine therapy in patients with ER-positive mBC (34:17) Selection of therapy for patients with locally advanced ER-positive, HER2-negative breast cancer (36:41) Therapeutic approach for patients who experience disease progression on a CDK4/6 inhibitor (39:33) Activity of alpelisib for ER-positive advanced breast cancer with a PIK3CA mutation (47:02) Side-effect profile of alpelisib (49:41) Case: A woman in her late 60s with high-grade, ER-positive, HER2-negative breast cancer and a 21-gene assay Recurrence Score (RS) of 52 receives adjuvant chemotherapy (52:54) Role of bone-modifying agents for patients with ER-positive breast cancer and bone metastases (58:04) Ongoing investigations of CDK4/6 inhibitors in the adjuvant setting (59:40) Effects of CDK4/6 inhibitors on immunity; potential for combination with immune checkpoint inhibitors (1:01:14) TAILORx trial: Adjuvant chemotherapy guided by a 21-gene expression assay for women with ER-positive, HER2-negative, node-negative breast cancer (1:06:19) Impact of clinical risk on prognosis and prediction of chemotherapy benefit by age and RS in the TAILORx study for patients with early breast cancer (1:07:46) Perspective on the use of gene expression assays to determine risk of recurrence and guide adjuvant decision-making (1:14:30) Cancer cell dormancy and risk of late recurrence (1:16:47) CME information and select publications  

Breast Cancer Update, Issue 3, 2019 — Part 2: Our interview with Dr Kaklamani highlights the following topics as well as cases from her practice: Efficacy and safety of the novel SERD elacestrant for ER-positive breast cancer; Phase III EMERALD trial evaluating elacestrant versus endocrine therapy (00:00) Incidence of ESR1 mutations; activity of elacestrant after disease progression on fulvestrant and a CDK4/6 inhibitor (02:14) Results from the Phase II ANETT trial of the mTORC1/2 inhibitor TAK-228 with tamoxifen as neoadjuvant therapy for ER-positive breast cancer (03:53) Novel approaches under investigation in the neoadjuvant setting (07:20) Perspective on the use of neoadjuvant therapy to optimize surgical outcomes for patients with ER-positive, HER2-negative breast cancer (09:43) Activity of CDK4/6 inhibitors for locally advanced ER-positive breast cancer (11:30) Case: A woman in her late 60s with ER-positive, HER2-negative breast cancer and 1 of 3 positive axillary lymph nodes receives a 21-gene assay RS of 18 (13:49) Role of the 21-gene expression assay in predicting chemotherapy benefit for patients with ER-positive breast cancer (15:56) Clinical and genomic risk to guide the use of adjuvant therapy for breast cancer (19:11) Case: A premenopausal woman in her late 40s with ER-positive, HER2-negative, node-negative breast cancer receives a RS of 19 (23:19) Clinical implications of the TAILORx trial comparing chemoendocrine therapy to endocrine therapy for patients with ER-positive, node-negative breast cancer and an intermediate RS (25:00) Tailoring adjuvant endocrine therapy for premenopausal women with ER-positive breast cancer (27:54) Benefit of endocrine therapy with or without chemotherapy for patients with ER-positive breast cancer and an intermediate RS; consideration of clinical and genomic risk in assessing the likelihood of disease recurrence (30:54) Case: A woman in her early 40s with ER-positive, HER2-negative breast cancer and metastases in the liver and bones attains a partial response to ribociclib in combination with endocrine therapy (35:24) Benefit with CDK4/6 inhibitors versus chemotherapy for ER-positive breast cancer with visceral metastases (37:57) Efficacy of ribociclib in premenopausal women; QT prolongation associated with ribociclib/tamoxifen (40:54) Comparison of the efficacy and toxicity profiles of abemaciclib, palbociclib and ribociclib for women with ER-positive mBC (42:24) Activity of CDK4/6 inhibitors as monotherapy; CNS penetration of CDK4/6 inhibitors (45:47) Monitoring and management of side effects associated with CDK4/6 inhibitors (48:07) Case: A woman in her mid-50s initially diagnosed with Stage II ER-positive breast cancer develops metastatic disease to the bone 8 years later and receives palbociclib and anastrozole (50:54) Perspective on the use of multiplex genomic assays to guide treatment decision-making for patients with ER-positive mBC (53:35) Results of the Phase III SOLAR-1 trial evaluating alpelisib for patients with ER-positive advanced breast cancer (55:54) Tolerability of alpelisib for patients with ER-positive breast cancer (57:54) Sequencing everolimus and alpelisib after disease progression on a CDK4/6 inhibitor (1:00:06) Case: A postmenopausal woman in her mid-30s with ER-positive mBC and BRCA2 and PIK3CA mutations receives talazoparib in the third-line setting (1:01:46) Choice of PARP inhibitor for patients with advanced breast cancer and BRCA mutations (1:04:58) Response and side-effect profiles of alpelisib (1:06:10) Selection and sequencing of therapy for patients with mBC and germline BRCA mutations (1:07:00) CME information and select publications  

An interview with Dr. Lynn Henry from University of Utah Huntsman Cancer Institute on "Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision-Making for Early-Stage, Operable Breast Cancer: Update of the ASCO Endorsement of CCO Guideline." This guideline update includes data from the MINDACT and TAILORx trials to clarify the recommendations for patients with hormone receptor-positive, HER2 not overexpressed, axillary node-negative early breast cancer. Read the full guideline at www.asco.org/breast-cancer-guidelines  TRANSCRIPT 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. Hello and welcome to the ASCO Guidelines Podcast Series. My name is Shannon McKernin. And today, I'm interviewing Dr. Lynn Henry from the University of Utah Huntsman Cancer Institute, lead author on "Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision-Making for Early-Stage, Operable Breast Cancer: Update of the ASCO Endorsement of CCO Guideline." Thank you for being here today, Dr. Henry. Thank you very much for the invitation. So this guideline was updated to incorporate new data from the TAILORx and the MINDACT trials. So can you give us an overview of these trials and their results? Sure. So patients with hormone receptor-positive, HER2 negative breast cancer, are generally treated with anti-estrogen treatment and are sometimes also recommended to have chemotherapy. Since these tumors don't always respond well to chemotherapy, tests have been developed that provide more information about how much benefit, in terms of reduction of the likelihood of cancer coming back, an individual patient is likely to get from treatment with chemotherapy. It is important that the benefit of a treatment outweighs the risk of toxicity from the treatment. Two of those tests are called Oncotype DX and MammaPrint. And they have recently been tested in large clinical trials. So TAILORx is a large prospective trial that tested the Oncotype DX assay. In the Oncotype DX assay, a tumor is tested to get more information about how likely a cancer is to return and how much benefit the patient is likely to get from chemotherapy. Scores on this assay can range from 0 to 100. Previously, a study showed that patients whose tumors had scores of 10 or less, and who received five years of anti-estrogen treatment, were very unlikely to have their tumors return. So chemotherapy is not recommended for them. For patients with higher scores, above 30, we also already knew that chemotherapy is likely to decrease the chance of cancers in those patients, and, so, therefore, we generally recommend chemotherapy for women with higher scores. In the TAILORx trial, the recently reported trial, more than 6,700 women with hormone receptor-positive, HER2 negative, lymph node-negative breast cancer had their tumors tested and were found to have Oncotype DX recurrent scores between 11 and 25, which is in that intermediate range or at the higher end of the low range. Before this trial was conducted, many people with tumors like these, in the intermediate range, were treated with both chemotherapy and endocrine therapy because we weren't sure how much benefit they would obtain from chemotherapy, and we didn't want to leave out a potentially helpful treatment. In this trial, patients were randomized, or randomly assigned by a computer, to treatment with chemotherapy followed by endocrine therapy or to treatment with endocrine therapy alone. The trial was mainly looking at whether leaving out chemotherapy would increase the likelihood of invasive cancer returning. And, luckily, overall, the trial showed that the likelihood of cancer returning in those patients who got endocrine therapy alone, without chemotherapy, wasn't significantly different compared to those who were treated with chemotherapy followed by endocrine therapy. They also looked, specifically, at the group of women who were 50 years of age or younger. So mostly premenopausal women. Now, this was an exploratory question, meaning it provides information that may be correct, but it hasn't been as fully tested as the main question about what do we do for all women? In these younger women, there appeared to be some benefit from chemotherapy in those whose tumors had scores from 21 to 25, and, also possibly, in those whose tumors had scores from 16 to 20. Therefore, we still consider giving chemotherapy to younger women with Oncotype DX scores in the middle range, from 16 to 25, but not to women over age 50. So that was the TAILORx trial. The MINDACT trial was a bit different. It was testing the MammaPrint assay and the trial also included primarily women with hormone receptor-positive, HER2 negative breast cancer. But in this case, most women's sorry lymph nodes were negative, although a few women had up to three lymph nodes involved. In that trial, patient's risk of disease recurrence was assessed in two ways. First, it was assessed based on clinical factors. So the size of the tumor, how many lymph nodes were involved, and the estrogen receptor, progesterone receptor, and HER2 receptors. Second, it was assessed based on genomic factors-- that was using the MammaPrint test. So if patients were low for both clinical factors and genomic factors, they only were treated with anti-estrogen therapy. If they were high for both clinical factors and genomic factors, then they were treated with chemotherapy followed by anti-estrogen therapy. However, if they were high for one and low for the other, then they were randomized to either endocrine therapy alone or chemotherapy followed by endocrine therapy. So it was a little bit of a confusing trial. In the MINDACT trial, those patients who were thought to be high risk based on their clinical risk, so the size of the tumor, the number of lymph nodes, but then found to be low risk on the MammaPrint assay. They found that there was no benefit to treatment with chemotherapy in terms of how likely a woman was to develop distant metastatic disease. And if they were low risk, based on the clinical assessment, then there didn't appear to be a benefit of actually doing the test, the assay, because chemotherapy wouldn't be recommended for the patient, regardless of the results. So that was the MINDACT trial. So what are the new and updated recommendations for the guideline? Yes, so in this guideline, we, based on the TAILORx trial, we made new recommendations for use of the Oncotype DX results. All of these results apply to women with hormone receptor-positive, HER2 negative, lymph node-negative breast cancer. So for women older than age 50, if they have an Oncotype score of 25 or lower, then clinicians may offer endocrine therapy and no chemotherapy. However, for women age 50 or under, if they have an Oncotype score of 15 or lower, 15, then, clinicians may offer endocrine therapy and no chemotherapy. But if the score is 16 to 25, then chemotherapy can be considered in addition to endocrine therapy. So it made a difference in that gray area in the middle. For all women with score 26 to 30, chemotherapy may be considered. And for scores above 30, chemotherapy should definitely be considered. The data from the MammaPrint trial actually aren't that new. Results from that trial were originally published in 2016. However, that was after the original guideline was published, so we wanted to add these results to these updated guidelines for completeness. For a patient with hormone receptor-positive, HER2 negative, node-negative breast cancer, who is thought to be at high clinical risk of breast cancer recurrence, if the MammaPrint assay shows low genomic risk, then treatment with chemotherapy can be avoided. If a patient is thought to be at low clinical risk, the MammaPrint should not be used as chemotherapy can be avoided regardless. And for a patient with hormone receptor-positive, HER2 negative breast cancer, but who has one to three positive lymph nodes, who is thought to be at high clinical risk of breast cancer recurrence, if the MammaPrint assay shows low genomic risk, then it is possible that chemotherapy could be avoided, especially if only one lymph node is involved. So I think the bottom line for this part is that both of these tests-- there are now women who previously would have been recommended to have chemotherapy that maybe now we can avoid chemotherapy based on using these assays on their tumors. So why are these changes so important and how will they affect practice? Yes, that's a good question. Before the publication of the TAILORx trial, we had good information about how to treat patients who had either very low or very high Oncotype scores. But we really weren't sure how best to treat those patients who scores fell in the middle. Now, we have important information to guide decisions about chemotherapy for patients with intermediate scores. For many patients with scores in this range, these new results mean they will be able to avoid chemotherapy and just get endocrine therapy. While these results don't give us answers for every patient, they do provide more information that oncologists can use when having discussions with patients about the benefits and risks of chemotherapy. And what does this mean for patients with early-stage invasive breast cancer? And what should they talk to their doctors about? So as a result of both of these trials, we now have additional tools that can help oncologists provide more individualized treatment recommendations for patients and really assess whether or not chemotherapy, in addition to endocrine therapy, is likely to provide benefits. Knowing which patients' tumors will respond to chemotherapy can help some patients avoid unwanted side effects from a treatment that's not likely to actually give them much benefit. Now, these tests aren't appropriate for everyone and don't provide all the answers, but they are an important step in the right direction for providing more personalized treatment for women newly-diagnosed with certain types of breast cancer. Patients should talk with their doctors about whether these tests are right for them when they're making important decisions about whether or not they should receive treatment with chemotherapy. Great. Thank you, Dr. Henry, for this informative overview of the guideline. Keeping these clinical practice guidelines updated is really crucial and it takes a lot of careful thought to ensure these recommendations represent the evidence. So thank you for coming on the podcast to discuss the "Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision-Making for Early-Stage, Operable Breast Cancer: Update of the ASCO Endorsement of CCO Guideline." Thank you very much for the opportunity to talk with you today. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/breast-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

TAILORx, Gut Bacteria and ICI, HIFU Voodoo, Rehabilitation quadshotnews@gmail.com @QuadShotNews

A virtual roundtable discussion with Drs Joseph A Sparano and Eric P Winer reviewing recent innovations in the treatment of early breast cancer. Comparison of patient risk classifications by genomic assays for patients with early-stage breast cancer (00:00) Prognostic gene expression assays in breast cancer: Are 2 better than 1? (06:13) Implications of gene expression assay results for therapeutic decision-making (07:51) Design and results of the Phase III TAILORx trial evaluating chemoendocrine therapy versus endocrine therapy alone for patients with ER-positive, HER2-negative, node-negative breast cancer and an intermediate 21-gene assay Recurrence Score® (RS) (11:19) Clinical implications of the TAILORx trial for treatment decision-making for patients older than 50 with ER-positive early breast cancer (EBC) (16:24) Prediction of chemotherapy benefit by RS for patients 50 years or younger with ER-positive EBC (17:51) Benefit with the addition of ovarian suppression to endocrine therapy for premenopausal women with ER-positive breast cancer at high risk for recurrence (22:18) Case (Dr Winer): A woman in her early 60s with Grade III ER-positive, HER2-negative, node-negative breast cancer has a 2.1-cm tumor and a RS of 25 (24:30) Risk of recurrence and benefit from chemotherapy for postmenopausal women with EBC (27:57) Significance of clinical risk category in prognosis and prediction of chemotherapy benefit by age and RS in the TAILORx trial (33:06) Perspective on the use of Ki-67 as a biomarker in breast cancer (36:11) Clinical and genomic risk to guide the use of adjuvant therapy for breast cancer (37:55) Implications of the TAILORx trial results for the use of neoadjuvant endocrine therapy (40:10) Case (Dr Sparano): A woman in her early 60s with Stage IIA ER-positive, HER2-negative lobular breast cancer, a RS of 19 and a high ESR1 RNA score receives adjuvant docetaxel/cyclophosphamide followed by anastrozole (45:45) Tolerability and quality of life during treatment with chemotherapy (50:09) Change in perspective for oncology professionals diagnosed with cancer (50:50) Impact of the RS-pathology-clinical (RSPC) score on the assessment of recurrence risk for patients with breast cancer (55:01) Case (Dr Winer): A woman in her late 30s with Grade II ER-positive, node-negative breast cancer and a RS of 20 receives treatment with ovarian suppression and tamoxifen (58:12) Case (Dr Winer): A woman in her late 50s with ER-positive lobular breast cancer, a 5.2-cm tumor, 1 palpable lymph node and a RS of 8 receives neoadjuvant endocrine therapy and a CDK4/6 inhibitor on a clinical trial (1:03:43) Case (Dr Sparano): A woman in her early 60s with Stage IIA ER-positive, node-positive right breast cancer (RS 7) and Stage IA left breast cancer experiences a good response to adjuvant anastrozole alone (1:07:21) Prognostic effect of the 21-gene assay RS for patients with high-risk ER-positive EBC and 1 to 3 positive nodes (1:10:19) CME information and select publications  

  William J. Gradishar, MD, of Feinberg School of Medicine and Northwestern Medicine in Chicago, chats with David H. Henry, MD, host of Blood & Cancer, to review some of the top breast cancer research presented at the 2019 annual meeting of the American Society of Clinical Oncology. Plus, in Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, talks about dealing with help-seeking and help-rejecting patients.   Show notes This episode discusses three randomized, controlled phase 3 trials that were presented at ASCO 2019:  KRISTINE trial (abstract 500) Design: Patients with HER2-positive breast cancer were randomized to receive either neoadjuvant trastuzumab, pertuzumab, and chemotherapy (docetaxel, carboplatin) vs. trastuzumab emtansine plus pertuzumab. Primary endpoint: Pathological complete response rate. Secondary endpoints: Toxicity, event-free survival, invasive disease-free survival. Conclusion: Docetaxel, carboplatin, and trastuzumab plus pertuzumab resulted in a higher rate of pathological complete response than did trastuzumab emtansine plus pertuzumab, but was associated with more serious adverse events. PREDIX trial (abstract 501) Design: Patients with HER2 positive and hormone receptor positive breast cancer were randomized to receive either neoadjuvant trastuzumab emtansine monotherapy vs. docetaxel, trastuzumab, and pertuzumab. Primary endpoint: Pathological complete response rate. Secondary endpoints: Toxicity and quality of life. Conclusions: Trastuzumab emtansine monotherapy was better tolerated while maintaining comparable PCR rate as the group which received docetaxel, trastuzumab, and pertuzumab.  TAILORx trial (abstract 503) Design: Patients with node-negative, estrogen receptor–positive breast cancer with an Oncotype DX recurrence score of 11-25 were randomized to receive either hormone therapy alone or hormone therapy together with combination chemotherapy. Primary endpoint: Rate of distant recurrence at 9 years.  Conclusions: There was no benefit from chemotherapy for younger women (aged 50 years or younger) with a recurrence score of 16-20 and at low risk clinically (small tumor size and favorable histologic grade). Those age younger than age 50 years with a score of 16-20, but high risk clinically, may benefit from chemotherapy. Much of the benefit derived from chemotherapy was because of ovarian suppression. Using the recurrence score in combination with clinical risk stratification allows clinicians to identify more young women who can be spared chemotherapy, and more young women who may benefit from antiestrogen therapy.   Show notes by Sugandha Landy, MD, a resident in the department of internal medicine, University of Pennsylvania, Philadelphia.   References J Clin Oncol 37. 2019 May 20 (suppl; abstr 500). doi: 10.1200/JCO.2019.37.15_suppl.500. J Clin Oncol 37. 2019 May 20 (suppl; abstr 501). doi: 10.1200/JCO.2019.37.15_suppl.501. J Clin Oncol 37. 2019 May 20 (suppl; abstr 503). doi: 10.1200/JCO.2019.37.15_suppl.503. Lancet Oncol. 2018 Jan;19(1):115-26. N Engl J Med. 2019 Jun 20;380:2395-405.    For more MDedge Podcasts, go to mdedge.com/podcasts Email the show: podcasts@mdedge.com Interact with us on Twitter: @MDedgehemonc David Henry on Twitter: @davidhenrymd Ilana Yurkiewicz on Twitter: @ilanayurkiewicz  

Dr. Antonio Carlos Buzaid, editor do MOC, Dra. Juliana Pimenta e Dra. Graziela Zibetti Dal Molin, autoras do MOC, comentam as apresentações de maior relevância em Câncer de Mama da ASCO 2019, passando por estudos esperados, como, TAILORx, MONALEESA-7 e IMpassion-130.

An interview with Dr. Fabrice Andre from Institute Gustave Roussy, Paris Sud University, in Paris, France on "Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Early-Stage Invasive Breast Cancer: ASCO Clinical Practice Guideline Update: Integration of Results from TAILORx." This update provides updated recommendations on chemoendocrine therapy for patients who present with a hormone receptor positive, HER2 not overexpressed, axillary node negative early breast cancer. TRANSCRIPT 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. Hello, and welcome to the ASCO Guidelines Podcast Series. My name is Shannon McKernin, and today I'm interviewing Dr. Fabrice André from the Institute Gustave Roussy in Paris, France, lead author on "Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Early Stage Invasive Breast Cancer. ASCO Clinical Practice Guideline Update: Integration of Results from TAILORx." Thank you for being here today, Dr. André. Thank you. So based on the title of this guideline, we know that this update was prompted by the results of the TAILORx trial. So can you tell us more about that trial and what its results were? Yes. So the TAILORx trial was a trial that randomized two treatment modalities, endocrine therapy versus chemotherapy endocrine therapy in patients who presented what we call an intermediate recurrence cohort. So before moving to the results, maybe we can discuss a little bit the background. What we knew from the past is the fact that patients who present a recurrence score below 11 should be treated with endocrine therapy alone, because they have the good outcomes. And patients who present recurrence score that is high, 31 but also can be more on 25, should receive chemotherapy. And we are talking about patients with hormone-receptor receptor positive, HER2-negative early breast cancer without lymph node involvement. And this is extremely important. So to summarize, it's a clinical trial that includes patients with hormone-receptor positive HER2-negative lymph node negative in early breast cancer, who present with recurrence score between 11 and 25. And the question is whether we can avoid adjuvant chemotherapy in these patients who present this intermediate score. So this is the general design and the question. In terms of research, what we have learned. We have learned that for patients above 50 years old, there is no difference between endocrine therapy and chemotherapy followed by endocrine therapy. So it means that this patient or these patients, we would consider endocrine therapy alone. Then, for patients below 50 years old, there was some difference. And I think we go further into the detail. There was some difference favoring the use of chemotherapy in the group of patients who presented with recurrence score from 16 to 25. And so what changes were made to the recommendations in this update of the guideline? So first, what were [INAUDIBLE] the previous guidelines. The previous guidelines were telling the clinician which genetic tests they could use in patients with hormone-receptor positive, HER2-negative early breast cancer. Now, the big change is that we are making guideline to explain how to use the test. And what is new is that we have made three important decisions. So first, for the patient is at the age above 50, now it is recommended clinician may recommend endocrine therapy alone for women older than 50 who present a recurrence score below 26. Before, the recommendation to use endocrine therapy alone was for patient's who present with low recurrence score. So it means now we have broadened-- we have increased the number of patients who could receive endocrine therapy alone and not receive chemotherapy. Then, for patients who present a recurrence score between 16 to 25 and who are below 50 years old, the clinician may offer chemotherapy followed by endocrine therapy, meaning that we are moving from [INAUDIBLE]. This intermediate score between 11 to 25 was what we call a [INAUDIBLE]. There was no recommendation on how to use the recurrence score. So right now, the update from the ASCO guideline is to provide recommendation on which treatment to administer in case a patient presents with intermediate recurrence score, and there are two different situations above 50 years old and below 50 years old. So why are these changes so important and how will they affect practice? So they will affect practice because for many reasons, I will say. In the US, they would affect practice because they increase the number of patients who will not receive adjuvant chemotherapy, because right now, we have an answer from randomized trial that we can avoid chemotherapy in women above 50 and from 11 to 25 recurrence score. So the impact in terms of public health would be that we could have a decrease in the use of chemotherapy or at least a better precision about who should receive adjuvant chemotherapy. Globally, this trial is going to provide an incentive and increase the level of evidence supporting the use of genetic tests. So it's important to remember that in a large number of countries, genetic tests are not reimbursed. But now, because lack of evidence, and here we have a randomized trial showing a level 1 evidence supporting the use of genetic tests. So we have two direct impacts of this trial. The first, inside US, where [INAUDIBLE] colleagues already use genetic tests, it provides better precision on who will receive adjuvant chemotherapy. And it's going to broaden the number of patients who will not receive. And globally, it's prospective randomized trial that we hope is going to incite payers to reimburse the genetic test in patients with early breast cancer. And so what does this all mean for patients with early stage invasive breast cancer? And what should they talk to their doctors about? So for patients with early breast cancer, so what are the messages for the patient? I think for the patient, the key message is that we are moving to precision medicine. We need a medicine that is extremely precise in terms of who should receive which treatments. And now, thanks to this trial, we are going to decrease the number of patients who receive chemotherapy, but also for the ones who will receive adjuvant chemotherapy, the value of the treatment, we need what the treatment provides to the patient is going to be very, very high. So what is important for patients is to understand that because of this trial, when we give them chemotherapy, we will know that the value of this treatment and the expected benefit is going to be higher than what we used to do in the past. So it's really fast forward and more precise medicine that consists in using molecular tests in order to provide or administer treatment with very high value. Great. Thank you Dr. André for your overview of this guideline update. This has been very informative. It's really good to hear that the expert panel has incorporated the latest research into the guideline and has carefully considered the implications for the patients. So thank you for coming on the podcast to discuss the "Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Early-Stage Invasive Breast Cancer: ASCO Clinical Practice Guideline Update: Integration of Results from TAILORx" Thank you. What people don't realize is we did hard work that ASCO doing with all these guidelines, and people are very committed, and they are [INAUDIBLE]. I mean, it's very reassuring for ASCO member to know that there are highly professional people who provide guidelines and it is also reassuring for the patients, for everyone. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/breast-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast, and refer the show to a colleague.

Chemotherapy has been a gold standard for treatment of breast cancer and often over-treats women who may not need this aggressive treatment to treat their breast cancer.  Dr. Sparano serves as the study chair for the TAILORx clinical trial sponsored by National Cancer Institute, the first clinical trial integrating a mulitparameter gene expression assay in clinical decision making for adjuvant therapy with early stage ER-positive, HER2 negative breast cancer.  The results will eliminate the use of chemotherapy for thousands of women.

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. 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. Learn more about these topics and other research presented at the 2019 ASCO Annual Meeting at www.cancer.net. If this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play. And stay tuned for additional Research Round Up podcasts coming later this summer. 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 conquer.org/support.

An interview with Dr. Lynn Henry from University of Utah Huntsman Cancer Institute on "Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision-Making for Early-Stage, Operable Breast Cancer: Update of the ASCO Endorsement of CCO Guideline." This guideline update includes data from the MINDACT and TAILORx trials to clarify the recommendations for patients with hormone receptor-positive, HER2 not overexpressed, axillary node-negative early breast cancer. Read the full guideline at www.asco.org/breast-cancer-guidelines  TRANSCRIPT 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. Hello and welcome to the ASCO Guidelines Podcast Series. My name is Shannon McKernin. And today, I'm interviewing Dr. Lynn Henry from the University of Utah Huntsman Cancer Institute, lead author on "Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision-Making for Early-Stage, Operable Breast Cancer: Update of the ASCO Endorsement of CCO Guideline." Thank you for being here today, Dr. Henry. Thank you very much for the invitation. So this guideline was updated to incorporate new data from the TAILORx and the MINDACT trials. So can you give us an overview of these trials and their results? Sure. So patients with hormone receptor-positive, HER2 negative breast cancer, are generally treated with anti-estrogen treatment and are sometimes also recommended to have chemotherapy. Since these tumors don't always respond well to chemotherapy, tests have been developed that provide more information about how much benefit, in terms of reduction of the likelihood of cancer coming back, an individual patient is likely to get from treatment with chemotherapy. It is important that the benefit of a treatment outweighs the risk of toxicity from the treatment. Two of those tests are called Oncotype DX and MammaPrint. And they have recently been tested in large clinical trials. So TAILORx is a large prospective trial that tested the Oncotype DX assay. In the Oncotype DX assay, a tumor is tested to get more information about how likely a cancer is to return and how much benefit the patient is likely to get from chemotherapy. Scores on this assay can range from 0 to 100. Previously, a study showed that patients whose tumors had scores of 10 or less, and who received five years of anti-estrogen treatment, were very unlikely to have their tumors return. So chemotherapy is not recommended for them. For patients with higher scores, above 30, we also already knew that chemotherapy is likely to decrease the chance of cancers in those patients, and, so, therefore, we generally recommend chemotherapy for women with higher scores. In the TAILORx trial, the recently reported trial, more than 6,700 women with hormone receptor-positive, HER2 negative, lymph node-negative breast cancer had their tumors tested and were found to have Oncotype DX recurrent scores between 11 and 25, which is in that intermediate range or at the higher end of the low range. Before this trial was conducted, many people with tumors like these, in the intermediate range, were treated with both chemotherapy and endocrine therapy because we weren't sure how much benefit they would obtain from chemotherapy, and we didn't want to leave out a potentially helpful treatment. In this trial, patients were randomized, or randomly assigned by a computer, to treatment with chemotherapy followed by endocrine therapy or to treatment with endocrine therapy alone. The trial was mainly looking at whether leaving out chemotherapy would increase the likelihood of invasive cancer returning. And, luckily, overall, the trial showed that the likelihood of cancer returning in those patients who got endocrine therapy alone, without chemotherapy, wasn't significantly different compared to those who were treated with chemotherapy followed by endocrine therapy. They also looked, specifically, at the group of women who were 50 years of age or younger. So mostly premenopausal women. Now, this was an exploratory question, meaning it provides information that may be correct, but it hasn't been as fully tested as the main question about what do we do for all women? In these younger women, there appeared to be some benefit from chemotherapy in those whose tumors had scores from 21 to 25, and, also possibly, in those whose tumors had scores from 16 to 20. Therefore, we still consider giving chemotherapy to younger women with Oncotype DX scores in the middle range, from 16 to 25, but not to women over age 50. So that was the TAILORx trial. The MINDACT trial was a bit different. It was testing the MammaPrint assay and the trial also included primarily women with hormone receptor-positive, HER2 negative breast cancer. But in this case, most women's sorry lymph nodes were negative, although a few women had up to three lymph nodes involved. In that trial, patient's risk of disease recurrence was assessed in two ways. First, it was assessed based on clinical factors. So the size of the tumor, how many lymph nodes were involved, and the estrogen receptor, progesterone receptor, and HER2 receptors. Second, it was assessed based on genomic factors-- that was using the MammaPrint test. So if patients were low for both clinical factors and genomic factors, they only were treated with anti-estrogen therapy. If they were high for both clinical factors and genomic factors, then they were treated with chemotherapy followed by anti-estrogen therapy. However, if they were high for one and low for the other, then they were randomized to either endocrine therapy alone or chemotherapy followed by endocrine therapy. So it was a little bit of a confusing trial. In the MINDACT trial, those patients who were thought to be high risk based on their clinical risk, so the size of the tumor, the number of lymph nodes, but then found to be low risk on the MammaPrint assay. They found that there was no benefit to treatment with chemotherapy in terms of how likely a woman was to develop distant metastatic disease. And if they were low risk, based on the clinical assessment, then there didn't appear to be a benefit of actually doing the test, the assay, because chemotherapy wouldn't be recommended for the patient, regardless of the results. So that was the MINDACT trial. So what are the new and updated recommendations for the guideline? Yes, so in this guideline, we, based on the TAILORx trial, we made new recommendations for use of the Oncotype DX results. All of these results apply to women with hormone receptor-positive, HER2 negative, lymph node-negative breast cancer. So for women older than age 50, if they have an Oncotype score of 25 or lower, then clinicians may offer endocrine therapy and no chemotherapy. However, for women age 50 or under, if they have an Oncotype score of 15 or lower, 15, then, clinicians may offer endocrine therapy and no chemotherapy. But if the score is 16 to 25, then chemotherapy can be considered in addition to endocrine therapy. So it made a difference in that gray area in the middle. For all women with score 26 to 30, chemotherapy may be considered. And for scores above 30, chemotherapy should definitely be considered. The data from the MammaPrint trial actually aren't that new. Results from that trial were originally published in 2016. However, that was after the original guideline was published, so we wanted to add these results to these updated guidelines for completeness. For a patient with hormone receptor-positive, HER2 negative, node-negative breast cancer, who is thought to be at high clinical risk of breast cancer recurrence, if the MammaPrint assay shows low genomic risk, then treatment with chemotherapy can be avoided. If a patient is thought to be at low clinical risk, the MammaPrint should not be used as chemotherapy can be avoided regardless. And for a patient with hormone receptor-positive, HER2 negative breast cancer, but who has one to three positive lymph nodes, who is thought to be at high clinical risk of breast cancer recurrence, if the MammaPrint assay shows low genomic risk, then it is possible that chemotherapy could be avoided, especially if only one lymph node is involved. So I think the bottom line for this part is that both of these tests-- there are now women who previously would have been recommended to have chemotherapy that maybe now we can avoid chemotherapy based on using these assays on their tumors. So why are these changes so important and how will they affect practice? Yes, that's a good question. Before the publication of the TAILORx trial, we had good information about how to treat patients who had either very low or very high Oncotype scores. But we really weren't sure how best to treat those patients who scores fell in the middle. Now, we have important information to guide decisions about chemotherapy for patients with intermediate scores. For many patients with scores in this range, these new results mean they will be able to avoid chemotherapy and just get endocrine therapy. While these results don't give us answers for every patient, they do provide more information that oncologists can use when having discussions with patients about the benefits and risks of chemotherapy. And what does this mean for patients with early-stage invasive breast cancer? And what should they talk to their doctors about? So as a result of both of these trials, we now have additional tools that can help oncologists provide more individualized treatment recommendations for patients and really assess whether or not chemotherapy, in addition to endocrine therapy, is likely to provide benefits. Knowing which patients' tumors will respond to chemotherapy can help some patients avoid unwanted side effects from a treatment that's not likely to actually give them much benefit. Now, these tests aren't appropriate for everyone and don't provide all the answers, but they are an important step in the right direction for providing more personalized treatment for women newly-diagnosed with certain types of breast cancer. Patients should talk with their doctors about whether these tests are right for them when they're making important decisions about whether or not they should receive treatment with chemotherapy. Great. Thank you, Dr. Henry, for this informative overview of the guideline. Keeping these clinical practice guidelines updated is really crucial and it takes a lot of careful thought to ensure these recommendations represent the evidence. So thank you for coming on the podcast to discuss the "Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision-Making for Early-Stage, Operable Breast Cancer: Update of the ASCO Endorsement of CCO Guideline." Thank you very much for the opportunity to talk with you today. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/breast-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast and refer the show to a colleague.

An interview with Dr. Fabrice Andre from Institute Gustave Roussy, Paris Sud University, in Paris, France on "Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Early-Stage Invasive Breast Cancer: ASCO Clinical Practice Guideline Update: Integration of Results from TAILORx." This update provides updated recommendations on chemoendocrine therapy for patients who present with a hormone receptor positive, HER2 not overexpressed, axillary node negative early breast cancer. TRANSCRIPT 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. Hello, and welcome to the ASCO Guidelines Podcast Series. My name is Shannon McKernin, and today I'm interviewing Dr. Fabrice André from the Institute Gustave Roussy in Paris, France, lead author on "Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Early Stage Invasive Breast Cancer. ASCO Clinical Practice Guideline Update: Integration of Results from TAILORx." Thank you for being here today, Dr. André. Thank you. So based on the title of this guideline, we know that this update was prompted by the results of the TAILORx trial. So can you tell us more about that trial and what its results were? Yes. So the TAILORx trial was a trial that randomized two treatment modalities, endocrine therapy versus chemotherapy endocrine therapy in patients who presented what we call an intermediate recurrence cohort. So before moving to the results, maybe we can discuss a little bit the background. What we knew from the past is the fact that patients who present a recurrence score below 11 should be treated with endocrine therapy alone, because they have the good outcomes. And patients who present recurrence score that is high, 31 but also can be more on 25, should receive chemotherapy. And we are talking about patients with hormone-receptor receptor positive, HER2-negative early breast cancer without lymph node involvement. And this is extremely important. So to summarize, it's a clinical trial that includes patients with hormone-receptor positive HER2-negative lymph node negative in early breast cancer, who present with recurrence score between 11 and 25. And the question is whether we can avoid adjuvant chemotherapy in these patients who present this intermediate score. So this is the general design and the question. In terms of research, what we have learned. We have learned that for patients above 50 years old, there is no difference between endocrine therapy and chemotherapy followed by endocrine therapy. So it means that this patient or these patients, we would consider endocrine therapy alone. Then, for patients below 50 years old, there was some difference. And I think we go further into the detail. There was some difference favoring the use of chemotherapy in the group of patients who presented with recurrence score from 16 to 25. And so what changes were made to the recommendations in this update of the guideline? So first, what were [INAUDIBLE] the previous guidelines. The previous guidelines were telling the clinician which genetic tests they could use in patients with hormone-receptor positive, HER2-negative early breast cancer. Now, the big change is that we are making guideline to explain how to use the test. And what is new is that we have made three important decisions. So first, for the patient is at the age above 50, now it is recommended clinician may recommend endocrine therapy alone for women older than 50 who present a recurrence score below 26. Before, the recommendation to use endocrine therapy alone was for patient's who present with low recurrence score. So it means now we have broadened-- we have increased the number of patients who could receive endocrine therapy alone and not receive chemotherapy. Then, for patients who present a recurrence score between 16 to 25 and who are below 50 years old, the clinician may offer chemotherapy followed by endocrine therapy, meaning that we are moving from [INAUDIBLE]. This intermediate score between 11 to 25 was what we call a [INAUDIBLE]. There was no recommendation on how to use the recurrence score. So right now, the update from the ASCO guideline is to provide recommendation on which treatment to administer in case a patient presents with intermediate recurrence score, and there are two different situations above 50 years old and below 50 years old. So why are these changes so important and how will they affect practice? So they will affect practice because for many reasons, I will say. In the US, they would affect practice because they increase the number of patients who will not receive adjuvant chemotherapy, because right now, we have an answer from randomized trial that we can avoid chemotherapy in women above 50 and from 11 to 25 recurrence score. So the impact in terms of public health would be that we could have a decrease in the use of chemotherapy or at least a better precision about who should receive adjuvant chemotherapy. Globally, this trial is going to provide an incentive and increase the level of evidence supporting the use of genetic tests. So it's important to remember that in a large number of countries, genetic tests are not reimbursed. But now, because lack of evidence, and here we have a randomized trial showing a level 1 evidence supporting the use of genetic tests. So we have two direct impacts of this trial. The first, inside US, where [INAUDIBLE] colleagues already use genetic tests, it provides better precision on who will receive adjuvant chemotherapy. And it's going to broaden the number of patients who will not receive. And globally, it's prospective randomized trial that we hope is going to incite payers to reimburse the genetic test in patients with early breast cancer. And so what does this all mean for patients with early stage invasive breast cancer? And what should they talk to their doctors about? So for patients with early breast cancer, so what are the messages for the patient? I think for the patient, the key message is that we are moving to precision medicine. We need a medicine that is extremely precise in terms of who should receive which treatments. And now, thanks to this trial, we are going to decrease the number of patients who receive chemotherapy, but also for the ones who will receive adjuvant chemotherapy, the value of the treatment, we need what the treatment provides to the patient is going to be very, very high. So what is important for patients is to understand that because of this trial, when we give them chemotherapy, we will know that the value of this treatment and the expected benefit is going to be higher than what we used to do in the past. So it's really fast forward and more precise medicine that consists in using molecular tests in order to provide or administer treatment with very high value. Great. Thank you Dr. André for your overview of this guideline update. This has been very informative. It's really good to hear that the expert panel has incorporated the latest research into the guideline and has carefully considered the implications for the patients. So thank you for coming on the podcast to discuss the "Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Early-Stage Invasive Breast Cancer: ASCO Clinical Practice Guideline Update: Integration of Results from TAILORx" Thank you. What people don't realize is we did hard work that ASCO doing with all these guidelines, and people are very committed, and they are [INAUDIBLE]. I mean, it's very reassuring for ASCO member to know that there are highly professional people who provide guidelines and it is also reassuring for the patients, for everyone. And thank you to all of our listeners for tuning into the ASCO Guidelines Podcast Series. To read the full guideline, go to www.asco.org/breast-cancer-guidelines. And if you've enjoyed what you've heard today, please rate and review the podcast, and refer the show to a colleague.

Subscribe to the podcast through iTunes and Google Play.    Dr. Clifford A. Hudis: Welcome to this ASCO in Action podcast. This is ASCO's podcast series where we explore policy and practice issues that impact oncologists, the entire cancer care delivery team, and the individuals we care for-- people with cancer. My name is Clifford Hudis, and I'm the CEO of ASCO as well as the host of the ASCO in Action podcast series. For today's podcast, I am delighted to have as my guest Dr. Ned Sharpless, the director of the National Cancer Institute. The NCI is the largest funder of cancer research in the world, and it has helped to drive many of the major prevention and treatment advances we've seen over the past 50 years. This includes things like HPV vaccination and the identification of the link between HER2 status and breast cancer outcomes and treatment, as well as new discoveries that have dramatically improved outcomes for childhood cancer. Dr. Sharpless, welcome, and thank you for joining me today. Now, we really have a whole lot to discuss, but before we get to our planned topics, I have to jump ahead and start with the president's State of the Union address, when President Trump mentioned that he wants to see $500 million appropriated for childhood cancers over the next decade. Can you talk a little bit about how you expect that, specifically, to play out? What will the NCI be able to do with those new specified funds for pediatric research? Dr. Ned Sharpless: Sure. I think childhood cancer-- childhood cancer is an area where the National Cancer Institute has had a long interest and a robust portfolio of research. And I think it is an area where we've made some progress, in terms of mortality, over the last few decades. But you have to say two things about childhood cancer. While progress has been good, and we're making-- more kids are surviving cancer therapy today than ever-- there's still a long way to go. Too many kids dying of cancer in the United States, and even the kids that we're able to cure have these significant lifelong survivorship challenges, in some cases. So the therapy that is curative may leave patients with side effects of surgery and chemotherapy and radiation for the rest of their lives. So better treatments for kids and less toxic treatments for kids are what we are really looking for. And with that amount of money, I think a good-- the thing that it appears to me that one could do to most quickly move the needle in childhood cancer-- which, as you know, is a collection of less common cancers, even rare cancers-- is really a more intentional effort at aggregating and using and linking clinical data with molecular data and other sorts of patient data, so that we can really learn from every child with cancer in the United States, so that we can really figure out what's working in certain populations and then disseminate that information as rapidly as possible-- without having, in all cases, to rely on slower clinical trial structures that are challenged for certain populations where accrual can be difficult. So I think that is the vision for the president's initiative, is to, with additional funding, allow for very aggressive, intentional, and organized data linkages and data aggregation so that we can learn from every trial and therefore treat every child's cancer in a better, more effective way. Dr. Clifford A. Hudis: You know, I think that's great. And that actually provides two different segues-- one I'm going to pick up right now, and one I want to come back to. The first is about data-- big data, specifically. We'll come back to that. The second is about the way the pediatric oncology community for years has really led in designing studies that could accrue the majority of children diagnosed with various specific diseases. And that leads me, that idea of eligibility and the structure of research, to ask about the way that you're thinking about modernizing clinical trials. This is something I know you wrote about in JAMA Viewpoint in the last couple of months. You addressed financial pressures, the need to increase overall rates of accrual to the trials, especially representing patients from underserved populations. Can you expand a little bit on that effort and what kind of progress you see as possible in the coming months and years? Dr. Ned Sharpless: Yeah, I think everything we do successfully in cancer today is in some ways the results of a clinical trial. And this is clearly one of the most important things the NCI does, in terms of moving basic science into patient care through experimental clinical trials. And it's an area where we-- frankly, a lot's changed in the last couple of decades. When I was a wee fellow, the clinical trials apparatus was very different from the way it is 20 years later today. And we need to make sure that we modernize the clinical trials process to keep up with the changes in our understanding of the biology and the new kinds of therapy we have for cancer. So that brings up a bunch of items that are areas where the NCI is really doing a lot of things. So, for example, one of the first problems I noticed when coming to the National Cancer Institute was that the clinical trials infrastructure, the big networks that we have for doing these kinds of trials, were under-resourced, that they had a funding problem. And they were becoming non-competitive with the trials sponsored by industry. And this showed itself in many ways, in accrual fees for patients, or the wait times to get the trial open, or the slow accrual once the trial was open. And so they were laboring under a number of problems. And so we decided we had to invest in the Clinical Trials Network and have been doing that and will be continuing to doing that in a number of ways-- through direct funding to attempt something like the National Clinical Trials Network or the NCORP, for example, the NCORP organization, but also by additional funding for biobanks and data aggregation initiatives, targeted clinical trials, et cetera. I think we've also-- there are some structural problems with the clinical trials that you alluded to. For example, eligibility criteria, I think, hadn't really kept pace with modern clinical trials. And I think ASCO and other groups have played a really important leadership role in identifying what are good eligibility criteria and which ones are not as necessary anymore. And then, do we have to have the same criteria in all the trials, and be more thoughtful about how those are used as a way to enhance accrual, because often we have a-- superfluous eligibility criteria can limit accrual. And increasing accrual by a variety of measures is really important. And we've thought a lot about how to do this through novel ways of clinical [? house ?] matching. I think one of the more successful efforts we've had in clinical trials accrual recently has been the MATCH trial, the NCI MATCH trial, which was able to accrue 6,000 patients at 1,100 sites in the United States, filling a targeted accrual two years ahead of schedule. It's the fastest-accruing trial in the history of the NCI. And I think one of the things MATCH teaches you is that if you have an interesting trial that's written in a nimble way that is open in the community-- that patients don't have to drive six hours to a cancer center, but can go to a local NCORP site, for example-- then those trials will accrue. We can accrue quickly, and we can accrue underserved populations, and we can accrue rare cancers. And that framework is more nimble than, say, the large phase III randomized trial run only at cancer centers that we had 10 years ago. There is still a role for large, randomized, phase III trials. The NCI is not backing away from that, or where we will support those. But I think, as we discussed in the JAMA piece, we really have to be thoughtful about where the NCI needs to be involved with those kinds of trials, compared to which of those should be supported by industry, for example. Dr. Clifford A. Hudis: It sounds like you're alluding to something I think you and I discussed even when you first got into your current role, which is the identification of those trials that industry should run, essentially, itself, and those trials that the NCI should support as complementary to industry trials. Can you expand a little bit on how you see that distinction and where you draw that line? Dr. Ned Sharpless: Yeah, the thing to know about clinical trials in oncology in the United States right now is most are actually paid for by industry. There's a huge pharmaceutical industry spend on clinical trials, and from my point of view, that's great. The fact that industry is paying for trials to develop therapies for cancer patients-- that's less money the NCI has to spend on those same questions. So we think that's a wonderful development and healthy for cancer research. But if that's the way it's going to be, then the NCI has to ask itself-- for the precious moneys that we have to spend on clinical trials, we need to use those in a way that's maximally effective and, in particular, not duplicative with what industry sponsors are doing. It's important to say, we do a lot of work with industry. So it's not just us either-or. Many of our trials, through these agreement processes called CRADAs, allow us to do trials with pharma sponsors and use their compounds in our trials. And that's a real boon to our research effort, as well. But there are certain kinds of trials that are very important where we really want to know the answer, but they're a bad fit for what industry is going to fund. For example, a de-escalation trial-- that's a trial where there's a standard of care that's pretty good, but the therapy is toxic. And so we'd like to see if we can get the same good outcome in a population using less aggressive therapy. A very important example of this was the TAILORx trial recently, where we showed that based on a genetic risk score, an RNA-based risk score of the breast cancer, women with estrogen receptor positive breast cancer-- many of them could forego cytotoxic chemotherapy and just take anti-hormonal agents and have the same good outcome in terms of their long-term survival. So that's a trial that is not going to be industry-led, for a variety of reasons. But I think it is the kind of question that's really important for patients. It's important, also, to say that de-escalation trials are hard to do. They require a lot of thought. They don't always work. And so they require these comprehensive thoughtfulness and infrastructure that the National Clinical Trials Network can provide. So an additional example is these multi-modality trials we have, where maybe two different agents come from two different pharmaceutical companies, and then there's some surgery and some radiation. There's very complex, multi-integrated care. And those can be very hard for a single sponsor to run, but, again, can be a very good fit for the NCI. And there are many other examples like this. But I think the real question we have to ask is, if our budget is limited and finite, what are the trials that the NCI really should do and lead on? Dr. Clifford A. Hudis: Yeah. And I think one of the points there is you need to conduct-- we need to conduct-- trials as efficiently as possible, getting the most so-called bang for the buck. You alluded to the fact that the NCI, along with ASCO, has been working on making trials essentially more efficient by making them more representative of the actual cancer population we end up treating. And a specific area of focus for us at ASCO, in this collaboration and also in our TAPUR trial, has been driving the eligibility age down below 18. My understanding is that this is something that you're adopting as a recommendation across the NCI, as well. I guess my question is, how broad and how quickly do you expect to see this implemented? Dr. Ned Sharpless: We have a number of efforts related to these barriers to accrual. You mentioned age as one of them and other sorts of exclusion criteria. And we've looked deeply and thought about this sort of care across the continuum of life-- both age limits on the less than 18 side, but also at the greater than 65-year-old side, where we see, often, eligibility criteria structured around a maximum age that don't often make a lot of sense. So that is one of several topics that we are addressing. As you know, we have a variety of networks and programs, and we fund a variety of kinds of trials. Some are led predominantly by the academic institution. Some are led through NCI networks. And so we are rolling out these policies, not in a one shot fits all way, but across these networks at different scales. They often require scientific buy-in from the other participants, and you know how that process works. I think this is an area, fortunately, where there is a lot of buy-in, where we're not having lengthy debates about whether or not we should do this. Really, the question is how we operationalize it and make it happen as quickly as possible. Dr. Clifford A. Hudis: That's great. And you know how strongly supportive we are, on lots of levels, for this effort and the related ones, in terms of barriers to accrual. I want to pivot, though, back to something that you introduced earlier about the big data. And my understanding is, in the annual plan and your bypass budget for 2020, you specifically called out the need to harness big data to speed up all of our work across the cancer research enterprise. And there are many companies, organizations-- we ourselves at ASCO have CancerLinQ-- that are involved in trying to collect data, share it, analyze it, and advance science and clinical care. But what exactly do you see as the NCI's role in facilitating this, and what do you think is our biggest challenge going forward? Dr. Ned Sharpless: Yeah, it's an interesting topic. I think the-- it's maybe two things to say off the top about big data in cancer research. The first is the NCI already has one very important example of how big data can transform a field, and that's The Cancer Genome Atlas, which later became the Genomic Data Commons. This is petabytes of genomic data that we make available in the cloud now to any researcher, basically, who is interested in cancer. And that set of data has led to thousands of papers and just a fundamental reorganization of how we think about cancer biology in many ways. And it's been a huge success, I would argue, and well worth the investment of the NCI to do it. And the data has been used in ways we never envisioned. We never thought of some of the papers and applications that would come out of the analysis of the Cancer Genome Atlas, for example. But the problem, then, one quickly sees, is that while that data set is great, it's limited. It doesn't have the clinical data, it doesn't have radiology and histology, it doesn't have-- we don't really have a way of binning big epidemiologic cohort data, for example. So the GDC, the TCGA, the Genomic Data Commons, proves how useful these kinds of data aggregation efforts can be, but also makes very clear what the shortcomings of our modern efforts are. The second thing to say is that this is a problem where the NCI is well-poised to be a leader, right? There are a number of issues around data sharing and data aggregation that really benefit from a Switzerland-like federal entity, a non-conflicted, dispassionate entity like the NCI that just wants to create the data structure in a way that's maximally beneficial for everyone, so that there are-- this is an area where the imprimatur of the federal government really allows us to play a role that would be hard for other groups to take on directly. And so I think this is a reason why so many groups have been looking to the NCI for leadership on this topic. So what are the challenges to big data? Well, I think that one challenge that has been spoken about a lot publicly is this issue of data hoarding by scientists and physicians and people who have these sets of data they don't want to share for academic competitive reasons. That is a problem. I'm not going to say that doesn't exist. But I don't actually think that's the biggest problem. I think a bigger problem around data sharing is just it turns out to be really hard to do. And by hard, I mean expensive. It turns out to be-- these various data sets were not created, initially, with the intent of sharing them. They're often in different formats. They're often governed by different kinds of data use agreements, which are governed by the consent form that the patient signed to have their data included. And so linking them can be both very technically difficult, from just a computer science point of view, and can also provide a lot of administrative and logistical hassles from the data sharing, data use agreement point of view. And so each one of these things is just something the NCI has got to work through, or someone like the NCI-- is figuring out how to link disparate data sets, how to get the right kind of data abstracted from charts that we want, how to develop the right work force to study big data with big data analytics, and then that is a big problem. So there are a number of areas where the NCI can address the challenges. And I think we'll make progress. I mean, the good news is that we understand these problems. This is not like we need to-- there's some fundamental problem of biology that we need to figure out. The bad news is that the problems are weedy, complex, and many, many layered, and require us working through them. But that's what we can do. We have support from the government for this. The moonshot had a lot of funding for data initiatives, which we've been employing to get these structures going. And now the Childhood Cancer Data Initiative, for example, I think could really-- that's a nice demonstration project, if you will, because it's the right size. Childhood cancer is about 16,000 cases a year. And so I think we can show what this radical data sharing, if you will, this data liberation project can do-- you know, that population and how useful it could be to larger groups of patients like lung cancer, breast cancer, things like that. So I think that these are the kinds of things the NCI can do with help from other federal agencies and academic partners and groups like ASCO. This is certainly not an area where we plan to go it alone. There are a lot of stakeholders and a lot of great ideas. And I think that by organizing and convening these initiatives, we'll make progress. Dr. Clifford A. Hudis: Well, I really, first of all, appreciate your calling out the fact that data hoarding in isolation is not the single biggest problem, because I think that's a frequently-cited limit. And I agree with you that it's less of an issue than all of the other ones that you highlighted. In that regard, I understand that you just announced a new office. I think it's the Office of Data Sharing? Can you expand on or explain how that relates to these challenges and what it's going to, hopefully, accomplish for us? Dr. Ned Sharpless: Sure. The Office of Data Sharing is something within our Center for Bioinformatics and Information Technology. It's getting stood up now. It's been around for about a year, even less than that. It has a new leader and a few FTs, and it has a number of jobs intended for it. I mean, there are a number of ways that we would like the Office of Data sharing to-- a number of problems that we think that the ODS can help serve with the external community in terms of data sharing, like these issues around consent and data privacy that I mentioned. But right now, an intense focus of that office, because it's something we really need to solve, are related, really, to the issue of accepting data and allowing access to NCI data at present. So we have this complex structure whereby academic investigators can give data sets to the NCI. That's harder than it sounds, because we have to make sure the data are of good quality and they're properly consented, and we understand the data usage agreements and that kind of stuff. And then we have a means to allow access to those data to accredentialed investigators. And there are a bunch of issues with that that are more complicated than you and I would want to go into right now. But I think that's consuming a lot of the bandwidth at that office right now, is the problems around, for example, the dbGaP entity, whereby different investigators give data to the NCI and the rest of the NIH. That has caused a bit of a bottleneck, and so we're trying to work through some of those issues. One thing, for example, that I think the ODS can do and is doing already is this sort of concierge-like function. For people who have large, valuable data sets that they'd like to give to the NCI, we should be able to take those data sets as quickly as possible. But something that's happened in the transmission of those data is that we've realized the quality isn't quite what we wanted or the format isn't exactly right, and so we have these questions, and they go back to the investigator. And there's this sort of cyclical loop that can take months and really substantially delay the process. And so the ODS is jumping in there early on and intervening on that loop and making sure the data are the right format and the right quality at the time of initial submission, so that we don't have this back and forth that wastes a lot of time. So I think those data access and data transmission issues are a prime focus for the office right now, although it has a much larger mission as it gets stood up. Dr. Clifford A. Hudis: Yeah, a little bit like CENTRA that Rich Schilsky runs for us here at ASCO, in terms of access. But at any rate, I want to take the remaining time we have, and maybe this is a speed round on the cancer research workforce. So a couple of quick questions, perhaps-- first of all, has the Cancer Moonshot Initiative had an impact directly on the kinds of awards that you're making available to researchers? And if so, how do you think that might evolve in the next couple of years? Dr. Ned Sharpless: I think the moonshot, as you know, was intended to focus on these 10 areas identified by a blue-ribbon panel that were thought to be ripe for clinical translation, just about ready to go into clinic and to benefit patients in a very direct, immediate way. So the moonshot per se didn't include funds for things like really hardcore basic science or training, although certainly moonshot moneys are being used to some extent in both those areas, as necessary, as part of these translational efforts. So I think that what the moonshot has done-- it's done a couple of things. So first of all, that most of the awards granted by the moonshot mechanisms are more these-- are not the traditional R01, but are more of these consortia and network grants. And I think we've built a lot of infrastructure for research efforts, say, in immuno-oncology or in pediatric cancer or in survivorship. And those networks will both-- well, they will live on beyond the moonshot in some cases, I'm sure. And those networks will provide integrated research efforts, but also some training opportunities. So most of those include junior scientists and junior clinical investigators, and so there will be some opportunity for the moonshot both to drive the scientific area of study and also provide some training opportunity for the new people coming up. Dr. Clifford A. Hudis: Well, speaking of junior and new, I listened to your conference call, I guess, about a week or two ago talking about the pay line. Can you expand on your plans to support young investigators right now, given the always-present constraints in funding? Dr. Ned Sharpless: Right. This is a particular problem for the National Cancer Institute, because we've seen this relatively-- there's no other word than "massive" influx in the number of applications for the so-called R01 grants, the independent investigator-initiated award at the NCI. And this is-- our award number is something up like 60% over the last nine years or so. So this rapid increase-- which is, in most ways, a very good thing. I mean, that says that new scientists are coming to our field with new ideas and new ways to treat cancer, and the NCI can pick among these many applications and fund the very best ones. But it has this pernicious bad effect for the academic investigator community, and that is that their individual chances of getting a grant are lower. If paylines are really the number of funded awards divided by the number of applications, and the denominator goes up faster than the numerator-- both are going up, but the denominator goes up faster-- then the paylines are going to go down. And we think this is particularly a problem for junior scientists, because established scientists have seen paylines come and go and funding realities change. But new scientists aren't as used to the life of the independent researcher and, we think, are most likely to either leave science or move out of cancer research to another area of science. And we'll have to try and minimize that from happening, to the extent possible. So one of the things we've done at the behest, in fact, of 21st Century Cures, which included language asking the NCI in the United States to do this, was really focused on these so-called early stage investigator, the ESI. So the ESI is faculty. That's someone who's gotten a job, generally in an academic institution, and is now writing their first R01 grant, their first independent scientist grant. And we've done a few things for this population. One thing that's really important is we give them a special payline. We give them, effectively, a higher chance of getting funding. So if, say, paylines are on the order of 8% now for all Comer grants, for ESIs they'll be more like 14%, right? So a significant-- or 12%, in that range. So, significantly higher than what the general community is. I want to point out, also, that paylines are lower than the actual success rates of the NCI, which is a better number. The reason success rates are higher is because we do fund a lot of grants outside of the score. It's a little bit of inside baseball. But generally, if you write a grant to the NCI, your chance of getting it is more like 12%. And if you're an early stage investigator, it's more like 16%. Dr. Clifford A. Hudis: Thanks, Ned. To switch gears a bit, I know you've worked with the NCI throughout your career. But now you've been at the Institute's helm for nearly a year and a half. Has your understanding of the NCI and its role in cancer research changed or evolved in this newest assignment? Dr. Ned Sharpless: I think it has to be said that I was an NCI watcher my entire research career, and I thought I knew the National Cancer Institute and the National Institutes of Health pretty well-- as well as one can know these organizations from the external perspective. But since starting at the NCI, I've really learned that this amazing organization is much larger than even I realized, and that the scale and scope of the NCI is truly both awe-inspiring and, in some ways, daunting. I had a series of meetings as I started as NCI director where I would learn about these sprawling comprehensive cancer prevention and control efforts or new areas of basic research or clinical trials. And I just really had had no idea that the NCI was involved in some of these activities. So it was very illuminating. In some ways, it's thrilling, the things the NCI is doing. But I think it also made very clear to me another thing that I think I knew at some level, but didn't really appreciate the full scale of this until becoming NCI director, and that's the issue of-- although the NCI is huge and has this great reach and comprehensive nature, we are limited in scale. Our resources are finite, and the NCI, therefore, is really forced to make these difficult choices about which areas of cancer research to fund and how best to address our mission of reducing cancer suffering. So I think I was surprised both by the scale and scope of the NCI, but also by the fact that, despite how big the NCI is, it still has significant limitations on what it's able to do and has to make these difficult choices. Dr. Clifford A. Hudis: ASCO recently launched the "I lived to conquer cancer" awareness campaign that spotlights federally-funded cancer researchers and the patients who inspire them. I want to close out our conversation today by asking you, why do you live to conquer cancer? Dr. Ned Sharpless: Yeah, I think like just about everybody in the United States, my life has been personally touched by cancer. I've had friends and family members get cancer, and my father even died from cancer. Both of my sisters are cancer survivors. So I think I have a real personal stake-- like everyone in the United States, almost-- in seeing the reduction of cancer suffering and conquering cancer, if you will. I also find the problem fascinating from an academic point of view. I was drawn to cancer research because I found the biological questions of cancer research so fascinating. So I live to conquer cancer from this intellectual point of view, as well. And lastly, I have the experience of being a doctor, of being a medical oncologist taking care of patients with cancer. And I've had the frustrating experience of having patients not do well who I thought, I wish we could have done more for-- as well as the experience of taking someone who has a pretty terrible cancer but yet driving it into remission with therapy and then watching that person effectively survive the disease and become cured of it over years. And that is so special and so thrilling to be a part of that as a physician. So I live to cure cancer because it's personally touched my life, because I am a scientist who is fascinated by the biology of cancer, and as a doctor I've had the experience of helping people survive their cancer. And once you do that once, you just want to do that over and over again. Dr. Clifford A. Hudis: That's really great, Ned. It's fascinating to hear why progress against cancer is personally so important to you. And I'm sure all of our listeners enjoy hearing that, as well. I want to thank you again for joining me for this ASCO in Action podcast and for all the work you do at the NCI and across the entire cancer care community. Well, thank you for having me. As you know, one of NCI's most important partners in this effort against cancer is really ASCO. And so it's great to speak to you today. And thanks for all the things that you guys do for patients with cancer. Again, thanks to all of you for listening today. Those of you who want to follow Dr. Sharpless on Twitter, he's @NCIDirector. And you can always follow me @CliffordHudis, as well as ASCO @cancer. If you do that, you can stay connected to our work, of course, on social media. You can also go to the NCI's website, which is NCI.gov. With that, again, I want to thank Dr. Sharpless for joining me today. And thanks to all of you for tuning in.    

Dr. Sparano is Professor of Medicine & Obstetrics, Gynecology, and Women's Health at the Albert Einstein College of Medicine, Associate Chairman for Clinical Research in the Department of Oncology at Montefiore Medical Center, and Associate Director for Clinical Research at the Albert Einstein Cancer Center. He also serves as Vice Chair of the ECOG-ACRIN Research Group and Vice Chair of the AIDS Malignancy Consortium. He is former director of the Hematology-Oncology Fellowship Program at Einstein/Montefiore,  co-directs the ECOG-ACRIN Young Investigator Program, and is a faculty member of the Calabresi K12 Oncology Training Program.  He is co-principal investigator of the Montefiore-Einstein Minority/Underserved National Community Oncology Research Program (NCORP) grant (in conjunction with Dr. Bruce Rapkin), which funds multicenter, NCI-sponsored clinical trials in cancer therapeutics, cancer prevention/control, and cancer care delivery research.  He is also the recipient of funding from the Breast Cancer Research Foundation that is supporting creation of a biospecimen bank designed to identify determinants of late relapse. Dr. Sparano is a practicing clinician who specializes in medical oncology and clinical and translational cancer research. His research has focused on developmental therapeutic approaches for breast cancer, lymphoma, and HIV-associated cancers, and therapeutic application of molecular profiling in cancer. TRANSCRIPT Welcome to the ASCO University Weekly Podcast. My name is Joseph Sparano, and I am Associate Director for Clinical Research at the Albert Einstein Cancer Center, and chief of the section of breast medical oncology at Montefiore Medical Center in New York. Today, we contrast two cases on adjuvant treatment of breast cancer. The standard treatment for hormone receptor positive, HER2 negative, early stage breast cancer is surgery, followed by endocrine therapy. Since the early 2000s, adjuvant chemotherapy has also been recommended to the majority of these women, but the added benefit from chemotherapy is modest for most. Many different gene expression assays have been developed to determine prognosis and identify which woman may be more likely to benefit from chemotherapy. One commercial test that is recommended in clinical practice guidelines is a 21 gene recurrence score assay. Based on the recently completed TAILORx study, it was known that woman with low recurrence scores on the 21 gene expression assay do well with adjuvant endocrine therapy alone. Whereas woman with high recurrence scores benefit from adjuvant endocrine therapy and chemotherapy. The TAILORx study clarified the best treatment option for women with an intermediate recurrence score, which was defined as a recurrence score of 11 to 25 in the trial. This is particularly important because the majority of patients fall in this intermediate risk category, up to 70%, in fact. Before we discuss the new evidence reported from this study, let's take a look at two intermediate risk cases. These two cases are very similar, yet the recommended treatments may be very different. Can you identify the key differences between these two cases? We begin with the first case. Case 1 is a 55-year-old postmenopausal woman with a node negative, ER positive, PR positive, HER2 negative breast cancer. The size of the tumor is 1.6 sonometers. The 21-gene recurrence score is 24, which is in the upper range of the intermediate risk category. Which option would you recommend as the best systemic treatment. The choices in this case include endocrine therapy alone or chemotherapy followed by endocrine therapy. The correct answer to this question is, A, endocrine therapy alone. We will discuss the rationale for this recommendation shortly, but first let's move on to the second case. The second case is a 44-year-old premenopausal woman with node negative, ER positive, PR positive, HER2 negative breast cancer. Like case 1, the size of the tumor is 1.6 centimeters and the 21-gene recurrence score is 24. Which option would be the best adjuvant treatment in this case? The choices here include endocrine therapy alone or chemotherapy, followed by endocrine therapy. The correct answer in this case is chemotherapy, followed by endocrine therapy. Both of these cases had nearly identical clinical presentations. That is, they presented with ER, PR positive, HER2 negative breast cancer, associated with negative axillary nodes, a primary tumor size of 1.6 sonometers, and a 21-gene recurrence score of 24. However, the key difference was the age at presentation, with one patient being in her mid 50's and postmenopausal, and the other patient being in her mid 40's and premenopausal. The TAILORx trial found that endocrine therapy was not inferior to chemotherapy plus endocrine therapy in the overall population with a mid-range 21-gene recurrence score of 11 to 25. However, there was an interaction between age, chemotherapy treatment, and recurrence score. About 1/3 of women who participated in the trial were 50 or younger. These women seem to have some chemotherapy benefit if the recurrence score was between 16 and 25. For those who had a recurrence score of 21 to 25, the absolute reduction in the risk of distant recurrence was approximately 7% at 9 years. For a woman who had a recurrence score of 16 to 20, the absolute reduction in distant recurrence by the addition of chemotherapy was about 2%. It remains unclear as to whether the benefit from chemotherapy in younger woman was due to a true cytotoxic effect associated with chemotherapy in eradicating micrometastatic disease, or a castration effect in inducing early menopause. Nevertheless, the findings from the TAILORx trial provide the highest level of evidence supporting the greatest level of precision in using the 21-gene assay to guide the use of adjuvant chemotherapy in early stage breast cancer. Thank you for listening to this week's episode of the ASCO University Weekly Podcast. For more information on the adjuvant treatment of breast cancer, including additional patient cases and opportunities for self-evaluation, visit the comprehensive e-learning center at university.asco.org. Thank you for your attention. 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.

Subscribe through iTunes and Google Play.   Welcome to this ASCO in Action podcast. This is ASCO's podcast series where we explore policy and practice issues that can impact oncologists, the entire cancer care delivery team, and those individuals we care for, people with cancer. My name is Clifford Hudis, and I'm the CEO of the American Society of Clinical Oncology. I serve as the host of the ASCO in Action podcast series. And today, I am really pleased to have as my guest Dr. Richard Schilsky. He is ASCO's senior vice president. And chief medical officer, and Rich is here to talk about our new clinical cancer advances report, which was just released. In clinical cancer advances, ASCO identifies the most important clinical research advances of the past year across the full range of cancers, and from prevention to screening to treatment and survivorship. The report also announces what ASCO has identified as our advance of the year. And for the first time in this year's report, we will debut what we believe are the research priorities with greatest potential to advance progress against cancer. Rich, welcome and thank you for joining me today. Thanks, Cliff. Great to be back. now let's start with what we always do. Every year, we announced the advance of the year, the one area of clinical cancer research that has demonstrated the most significant progress in a year's time. And we've seen tremendous progress in the treatment of rare cancers, earning it the 2019 advance of the year recognition. Rich, can you talk about why this area was chosen? Why is this particular line of research so important for individuals with cancer? Well, first, let me start with a definition of what we mean by rare cancers. And generally, what we're talking about are cancers that are diagnosed with a frequency of less than six cases per 100,000 cancer diagnoses each year. Collectively, though, because there are many kinds of rare cancers, overall rare cancers comprise about 20% of all new cancer diagnoses every year. But those numbers may not even tell the full story, because as we learn more and more about the molecular subtyping of cancer, what we're learning, of course, is that there are many very, very rare mutations and fusions and other genomic alterations that occur in a very small proportion of even common cancer diagnoses. So the patient with lung cancer, who has a RET fusion that occurs in about 1% of all lung cancer cases, that begins to become a very rare subset, even though it's overall a common disease. So we're going to be dealing more and more with this general area of rare cancers. But the reason that it's so important to single this area out, of course, is because historically, we haven't been able to learn very much about these rare cancers, simply because they are rare. There aren't very many of them that occur each year. Therefore, they're difficult to study. It's difficult to complete clinical trials. It's difficult to find patient samples to be able to understand the underlying biology of these diseases. And yet, many of them are refractory to standard treatments. Many of them have a very aggressive clinical course. And for patients who are affected by one of these rare cancers, they desperately need new treatments. And this year, we're seeing, for the first time, some real progress being made in a number of these rare cancers. I'll give you some specific examples that we called out in the report. So for example, although thyroid cancer is a very common form of cancer, anaplastic thyroid cancer represents only about 2% of all thyroid cancers. And of those anaplastic thyroid cancers, about 16%-- so now we're talking 16% of 2% have a BRAF mutation. But it's clear now that treatment with BRAF directed therapy produces a very high response rate in this rare group of individuals who have BRAF mutant anaplastic thyroid cancer. Another example, take the drug we're all familiar with, trastuzumab. We know now, of course, that trastuzumab is effective not only in breast cancer, but also in gastroesophageal adenocarcinoma that's HER2 amplified. And there's emerging data that HER2 directed therapy may be active in other tumor types, where the HER2 gene is amplified. And one of those is uterine serous carcinoma. So uterine serous carcinoma is a rare subtype of endometrial cancer. And about 20% or 30% of those patients have a HER2 amplified gene driving their tumor. And trastuzumab has been shown to be an effective therapy in those patients as well. Last example I'll give you right now. A tumor that most oncologists probably will never confront in their practice, tenosynovial giant cell tumor. This is a very rare soft tissue tumor that occurs in the joints, typically of young adults, typically is refractory to all standard known cancer treatments. And yet, this year, we saw very promising results reported for a new class of anticancer drug, a CSF 1 inhibitor, called pexidartinib, that produced a 40% objective response rate in patients with these advanced tumors, compared to a placebo treated control group. So we're starting to make real progress in treating these rare cancers, particularly when we can begin to understand their underlying biology, and develop a therapy that's directed at the key drivers. It sounds to me-- I mean, in listening to that wonderful list of successes, that we've rolled up a process and an approach to drug development and science into a category that is appropriately called rare cancers. Because when you think about the way you presented it, which I think is lovely, first, rare cancers, as a group, aren't rare is what you said. Two, rare cancers cross from the rare histologies to include some of the common histologies. But the underlying theme, if I think about the way we present this, is a deeper understanding of the driver mutations, allowing us to move a little bit off of histology towards genomics to define these diseases. And that's not to say that genomics is the only way we're going to make progress. But the unifying theme in these cancers is probably that shared trait of an alteration and a driver mutation and an available drug. And that's the advance that's helping us with rare cancers. Is that a fair roll up of that? I think that is very fair. And you can think about it in terms of a common histology, like lung adenocarcinoma, having a large number of rare genomic subtypes, each of which comprises a rare cancer, if you will. Alternatively, you could think about it as in the trastuzumab example, of saying, well, if you look at the universe of HER2 driven tumors, those HER2 driven tumors comprise a whole bunch of different histologies. But they all are responsive to HER2 directed therapy. And so you know, as we understand the underlying biology of cancer much more clearly, it's moving us away from the long held view that the way you diagnose cancer is looking under the microscope. And if you see something that you see only very rarely, you say it's a rare cancer, to we're not going to interrogate the cancer if we see a rare genomic alteration that occurs infrequently in the population of cancer patients. That's what we're going to call a rare cancer. Yeah, I just say think it's almost like an introduction or a preview of an interesting future where more and more of the cancers we treat may be selected on this basis, rather than their conventional light microscopy appearance, right? To be sure. I mean, we know still that context is important. Not all of these molecular drivers behave in the same way in every tumor type. We already have examples where not all the targeted therapies work equally well against the same alteration, again, in every tumor type. But slowly, but surely, I think the science is moving us toward a day where we will be identifying cancers, primarily, if not exclusively, by their genomic profile. It may not be a single driver. It may be a signature. But that is ultimately is what we use to direct therapy. So to some degree, this is a fulfillment of a multi-year view that we've had about where to invest in cancer research, and the fruits, I think, are obvious. But this wasn't the only advance that we reported on last year. It's the one we named as the advance of the year. But what were some of the other advances that we called out for recognition? So as in the last several years, where we named some aspect of immunotherapy as the advance of the year, this year we continue to see progress in immunotherapy of cancer, particularly with extending the range of indications for many of the immune checkpoint inhibitor drugs, as well as new indications for CAR T cell therapies. So that continues to be a rapidly emerging area where there's a lot of progress continuing to be made. We continue to make progress how with the introduction of second and third generation targeted therapies. We've come to understand, of course, that many targeted therapies although they work well for a period of time, cancers ultimately develop resistance, patients need additional treatment options after the first line of targeted therapy. And of course, the science has responded by giving us the insight as to the mechanisms of resistance, which has led to the development of second and third generation inhibitors that can effectively overcome the treatment resistance. We're seeing this particularly in lung cancer, particularly with drugs recently introduced like osimertinib, which is effective against the T790M mutation, the common resistance mutation in EGFR mutated non small cell lung cancer. And interestingly, some of these drugs are also now showing much greater effectiveness in treating or even preventing the onset of brain metastases in lung cancers that commonly spread to the brain. So this has opened up actually a whole new area of research on effectively treating and preventing brain metastases in those tumor types, where there's a high propensity for such metastases to occur. The last thing I'll mention as another area of continuing progress is the continuing development of new biomarker strategies to help us refine the way in which we select patients to receive treatment. And certainly, this last year, the big news were the results of the so-called TLRX trial in breast cancer, a test, a gene expression profiling test, that clearly indicates that there is a substantial proportion of women with hormone receptor positive early stage breast cancer who can safely forego treatment with adjuvant chemotherapy with no detrimental effect. And this type of test I think is now going to really move us even further down the road of precision medicine, because it's allowing us to identify those patients who are most likely to benefit from adjuvant chemotherapy. They should get treated, and they will certainly benefit. But it also is allowing us to identify those patients for whom adjuvant chemotherapy is unnecessary, and who can be spared both the physical toxicity and the financial toxicity of adjuvant treatment. The more of those tests that we can develop, going forward, the better we'll be able to refine prognosis, the better we'll be able to apply adjuvant therapy in the future. I think one of the subtleties here is this highlights something we almost touched on before, which is precision medicine doesn't have to be only about gene rearrangements. There are multiple paths towards some degree of precision in treatment selection for individual patients. And this is, I think, a good example of that. It also is a good example of the fact that precision medicine is not actually just about treatment selection. It's about risk assessment, risk stratification, assessment of prognosis, identifying early recurrence, as well as directing patients to the right therapy at the right time, based on the biological characteristics of their cancer. So one of the things that we've done this year, and it's a first for us, is to announce a set of research priorities. These represent areas that our leading volunteers and others have identified as needing urgent attention. They are areas where the progress is promising, but not fulfilled completely. Can you talk a little bit about the motivation for creating this kind of a research agenda, as well as a criteria for actually selecting the specific research priorities? So obviously, you know, our field is advancing very rapidly. But there are still very many unmet medical needs. There are many clinical conundrums that oncologists face every day in practice. And we felt that given all the potential directions that research could take, ASCO is in a strong position to be able to at least begin to describe those areas, where we thought the potential benefits in patient care would be greatest, and could be realized soonest. ASCO, because we are the physicians who treat patients with cancer, we have a pretty good sense as to what the unmet medical needs of our patients are, what the lack of evidence is that our doctors struggle with every day in making clinical decisions with patients, where the field needs to continue to grow and to develop new information, to help fill those evidence gaps. So we felt that we could take a stab at setting a research agenda, and putting out there where we thought the unmet needs, where we thought the opportunities were ripe for investment in research, and trying to articulate how, if we were successful in fulfilling those research needs and priorities, the field would ultimately be transformed. So that's what we've done with the nine research priorities that we are offering this year. So the nine priorities that's important for readers in a moment, if they go look at this or pick up our publication to recognize, they're not rank ordered. They just happen to be nine. Maybe next year, there'll be fewer or more. And the second thing is in no particular order, as I understand it, we've divided them into a couple or maybe three big buckets. One is essentially the issue of who really benefits from IO, the advance that you already talked about, as a multi-year call out from us. The second is really a little bit about health care disparities and precision medicine all rolled up in the concept of special populations. And related to that is access to research itself. And then the third is something which we always worry about, but have, I think struggled with as a field for decades, and that is reducing cancer risk, along with screening, which is surprisingly still controversial in many settings. We'll talk a little bit more about some of the specifics, but I would just remind everybody listening that you can find a list of these nine research priorities if you go to our website asco.org/cca. So Rich, as you think about the nine areas that are rolled up in those three broad areas, can you talk a little bit about how specific research would potentially transform patient care? And you've set a relatively short timeline for results in introducing this. And what kind of resources might these projects need? If you take the first area, for example, of essentially getting the right treatment to the right patient at the right time, you know, we've touched on some of these themes already. Look at the results so far with immune therapy for cancer. It's remarkable that a significant, although still small fraction of patients across multiple tumor types, who receive an immune checkpoint inhibitor, will have prolonged disease control, 20% or so of patients apparently surviving, without disease progression, or even disease free for many, many years in melanoma and diseases that previously were death sentences for patients. The question is why is it only 20%, and who are they? Because these drugs are toxic. They're expensive. And what we'd like to be able to understand is, what are the characteristics of the tumor or of the host or of the treatment that makes the treatment so effective in a proportion of patients, so that we can then learn how to increase its effectiveness in those groups of individuals, where it has so far been less effective. The same is true, as we touched on a moment ago, regarding adjuvant post-operative therapy. If you think about solid tumors, broadly speaking, roughly 50% of patients with a newly diagnosed solid tumor are cured by surgery alone. They don't need and can't benefit from adjuvant therapy. Of the remaining group, who are at higher risk of recurrence. Many of them will not benefit from whatever adjuvant therapy they might receive. So what we observe in most clinical trials of adjuvant therapies are relatively small absolute improvements in say disease free and overall survival for the entire population of patients treated. But of course, what that likely represents is a substantial benefit for a small proportion of that population. So what we are suggesting in this research priority is additional research, similar to what we saw presented this year with the TAILORx study, that allows us to understand the biology, the biomarkers, the testing that can be done to identify the patients most likely in need of and those who will most likely benefit from adjuvant therapy. And then the third area within this general theme goes back to immunotherapy and the enormous promise of CAR T cells, which so far, has been realized almost exclusively in patients with hematological malignancies. So that's wonderful. And we want to extend that benefit as far as it will go. But the question is, can those treatments be effective in solid tumors, which generally have a much more complex biology than many human hematological malignancies, and how do we develop CAR T cell therapies that can be effective in the solid tumor setting, that can be delivered to a solid tumor patient population, and ideally, and this may still be a bit of a pipe dream, can we develop CAR T cell therapies then that can be developed and administered off the shelf, so that they don't have to be custom made for each individual patient, which drives up the complexity and the cost of treatment. So those are the key elements of this initial theme. And in a similar way, we would have similar, or we would have short term plans for the other areas that we haven't gone into detail here. And again, I would remind listeners that they can go through our whole list of ideas in terms of areas of focus at asco.org/cca. Right? Absolutely. And when they do that, what they'll find are that we are calling for increased research in precision medicine and pediatric cancer. We're calling for increased research that's necessary to optimize the care of older adults with cancer. We're calling for research on how to ensure more equitable access to cancer clinical trials, so that all patients can benefit from those studies, and we can make progress more quickly. And then finally, of course, we're very interested in learning more about how to reduce the long term consequences of cancer treatment. The pediatric oncologists have actually been quite successful at this, because first of all, they've been very successful at curing children. And now, they've been able to show that they can begin to pull back on certain components of therapy in a very thoughtful and well studied way, so as to not diminish the chance of cure, but to diminish the risk of long term side effects of treatment. We, of course, want to have more research done, addressing the challenge of obesity in this country and its link to cancer risk, cancer progression, and cancer treatment, and then finally, to identify strategies to better understand the biology of so-called pre-malignant lesions, so that we can understand which pre-malignant cancers are the ones that are destined, in fact, to become invasive cancer. That latter touches on a theme we could talk about another day which is the building, the emerging drive to rename some of those cancers, as something less than cancer, because of their lack of at least acute life threatening potential, right? We could talk about that another day, and we should. Yes. So one of the things that I think is always important to point out is we can do all of this work, but of course, we are part of society, and we're dependent upon various sources of funding and other resources in terms of public policy. We are dependent on government ultimately for support, as well as private support. And I think this clinical cancer advances report highlights that there are policies that would help us improve and accelerate clinical cancer research. Some of them are obvious. We talk about them in other podcasts, increasing access to clinical trials, covering the routine quest of care for trial participants, and indeed, increasing overall federal funding, not in an unpredictable way, but in a steady way, that allows us to make multi-year plans across our community. Given all of that, what steps do you think ASCO members, specifically, could take to support us? And I would take it a step further. What should they be telling their representatives in Congress in terms of these policies? What should they be telling them in terms of supporting these critical areas of cancer research and how can they make an impact? It's clear that essentially all progress that we make in developing new treatments for cancer ultimately gets linked back to federally funded support for basic science research. All of the insights that we've developed in terms of what causes cancer, how it progresses, which are the high risk populations, so much of that information comes from data sets and other basic laboratory studies, funded by the NIH or the National Cancer Institute. Of course, the NCI has in place a robust national clinical trials network publicly funded that supports clinical trials that would never be done by a commercial sponsor. In fact, three of the rare cancer studies that I mentioned earlier during this podcast were done with support from federal funding. Those studies, because they are rare cancer, small populations are not studying tumors that represent a large market for a new pharmaceutical product. They're not going to be done by a commercial sponsor. We need federal support. And we need our members to point out these kinds of examples when they go to talk to their representatives in Congress. And I would urge our members to not only go to talk to your representative, but to bring a patient with you. The patient tells a story far better than we can. And having the patient at your side and having the patient tell their own story about how they benefited from federally funded research is very powerful. In order to reach your member of Congress, ASCO's trying to make that as easy as possible, and you can do that by going to ASCO's Act network at asco.org/actnetwork. That's great. I mean, we've covered a lot of exciting progress, I think, this year. And readers who take the time can dive far more deeply into this discussion with our publication. But what would you say is the main takeaway, the thematic takeaway that you hope people will get from this year's clinical cancer advances report? To me, I think what we continue to see this year, and we have seen in recent years is that the more deeply we understand cancer biology, the more that will quickly lead us to new therapeutic approaches that will be far more effective, and hopefully, less toxic, and maybe most importantly, more enduring than the common therapies that we've had available to us in the past. Our field is clearly moving to a day when immunotherapy will be central to cancer care, when every patient will have their cancer genotype well understood, and where therapy decisions will be informed by that deeper understanding of each patient's biology. So you almost did this, but I'm going to push you a little more. In the same way that we're now calling for what should be done next in terms of research, if you could actually look into the future, what areas of progress against cancer would you expect or maybe hope to see, just 12 months from now, when we do this report again? I hope that one of the things we'll see is rapid progress in developing, not necessarily novel biomarkers as unique tests, but novel biomarkers signatures. I think it's becoming increasingly clear that in order to select patients optimally to receive immunotherapy, and even to select patients to receive certain precision medicines, that a single biomarker is not necessarily the optimal selection strategy. For immunotherapy, we may need to see a signature that represents some characteristics of the tumor, some characteristics of the patient, maybe even some characteristics of that patient's microbiome in order to figure out who is most likely to be susceptible to which immunotherapy approach, and the same is going to be true, I think, for even the now common precision medicine approaches with small molecules. We're trying to understand how molecular pathways and networks work inside the cell can suggest to us not which single targeted therapy to use, but which combination of targeted therapies to use for each individual person. This kind of work is on the horizon. It's complicated, involves lots of complex algorithms. But my hope is that this will move us to a future where we can take the results of a test on a patient's tumor and integrate information of various sorts and come out with a more precise estimate of what's likely to be the best treatment for that person. And you think that we could see some of those results even as soon as just 12 months from now, or is this a longer term hope? I think we will begin to see some of these types of approaches appearing at an ASCO meeting in 2020. Well, that's really exciting. I think it's really both uplifting, and I think challenging to hear where we are, because of course, as is always true in science, every answer begets many more questions. And in our world, every bit of progress identifies new challenges. And I think that's what's summed up in a lot of what's in this report now, right? Absolutely. But you know, I think for the first time, you know, ASCO is trying to articulate where we see the greatest opportunity. And we hope to be able to do this each year in the coming years. As you said earlier, it may not always be nine research priorities. Some of that might even be repeated year to year, because we won't solve every one of these in a year from now. But we will modify these. We will improve upon them, and they will change as the science advances, as the questions evolve, and as the opportunities continue to develop. Well, rich I want to thank you for joining me today for this ASCO in Action podcast. I'll remind everybody, we have a mission at ASCO to conquer cancer through research, education, and promotion of the highest quality cancer care. And this clinical cancer advances report really does help us meet that mission, by increasing awareness of the progress we're making, but also, as you point out, identifying the critical importance of the entire community's engagement in research and high quality care. That is pointing out just how important all that is in terms of delivering on the promise of all of our progress. I encourage listeners, again, to read the full report by visiting asco.org/cca. And until next time, I thank everyone for listening to this ASCO in Action podcast.

It was among the biggest cancer news stories of the year: A new study – the largest breast cancer treatment trial ever conducted – showed no benefit from chemotherapy for 70 percent of women with the most common type of breast cancer. As the Washington Post described, that means: “most patients who have an intermediate risk of a cancer recurrence — a group that numbers 65,000 women a year in the United States — can avoid chemotherapy and its often debilitating side effects.” The TAILORx trial, as it is known, is helping change everyday procedures in the everyday lives of patients around the world. And the lead author is our guest today. Dr. Joseph Sparano is Professor at Albert Einstein College of Medicine. He is Vice-Chair, ECOG-ACRIN Cancer Research Group and has been a BCRF Investigator since 2012. I asked Dr. Sparano about the TAILORx study and how it feels to have been part of such landmark work. But I also asked Dr. Sparano about what’s next – about new work he’s doing around breast cancer recurrence – specifically relapses that occur many years after original diagnosis. 

Will you need chemo? Results from TAILORx study. by SurvivingBreastCancer.org

Women with early-stage breast cancer who might have normally received chemotherapy under current standards may not actually need it, according to a ground breaking study that is expected to change the way we look at early stage breast cancer. Melita Charles, Breast Surgeon at Ashikari Breast Center, discusses the TAILORx clinical trial, which can help women make the most informed decisions about their cancer and may change the landscape of early stage breast cancer treatment.

On this episode of SO Files, Alston, Brad and Linda take a closer look at the recently published TAILORx Clinical Trial Published in NEJM by Sparano and colleagues. The study expands the existing clinical application of the Oncotype DX score. If that score sounds familiar its because it has been making its way into clinical practice over the past few years (see our last episode on the new AJCC guidelines!). We explain the origin of the score, how it has been incorporated into clinical practice thus far, and how this trial addresses a large gap in the existing literature.

New findings from a groundbreaking Trial Assigning Individualized Options for Treatment (Rx), or TAILORx trial, show no benefit from chemotherapy for 70 percent of women with the most common type of breast cancer.Dean Tsarwhas, MD, Medical Director, North Region, Cancer Services, Northwestern Memorial Healthcare, joins the podcast to explain these findings and to let women know that this could help identify women with a low risk of recurrence who could be spared chemotherapy.

The TAILORx study demonstrated that most women with a specific early-stage breast cancer and midrange score on the Oncotype Dx test do not need chemotherapy after surgery. These findings will spare thousands of women from the harmful effects of chemotherapy. We spoke with Andrew Paramore from Genomic Health (CA, USA)to discover insider details of the trial and what’s next for TAILORx.

Dr Kaklamani talks to ecancertv at SABCS 2015 about results from the ongoing, prospective Trial Assigning Individualized Options for Treatment (TAILORx) involving more than 10,000 women with estrogen receptor (ER)-positive, HER2-negative, axillary node-negative breast cancer. TAILORx has been designed to demonstrate whether the Oncotype DX can be used to correctly identify women who may not need chemotherapy and could safely be given endocrine treatment alone. In the study, patients with a low (25) RS assigned to chemoendocrine therapy. Women with an intermediate (11-25) RS were treated with chemoendocrine therapy or endocrine therapy alone and results of that study arm are expected in the future. Dr Kaklamani discusses the data from the low risk group who received endocrine treatment alone. Five-year rates for distant relapse-free interval, the relapse-free interval, invasive disease free survival, and overall survival were a respective 99.2%, 98.5%, 93.7%, and 98.2%. The findings show that despite meeting guidelines for recommending or at least considering adjuvant chemotherapy based on classical clinical and pathological features, the risk of recurrence was very low at 5 years. This population of women patients may be very effectively treated with endocrine therapy alone without chemotherapy.

Most patients with ER-positive, HER2-negative, node-negative breast cancer should be presented with the option of participating in the TAILORx trial and of having the Oncotype DX assay performed outside of a trial.