Podcasts about monaleesa

Metastatic Hormone Receptor-Positive Breast Cancer truly represents the frontier of Medical Oncology, with life expectancy creeping up to and beyond five years. This week, we discuss Monaleesa-2 (Ribociclib), Paloma-2 (Palbociclib) and, of course, highlight the importance of Monarch-3 (Abemaciclib). The great CDK debate continues, and while the phase three trials have a clear winner, it's important to discuss the benefits and cons of each.Studies discussed in the episode:MONALEESA-2PALOMA-2MONARCH-3 (Mention)For more episodes, resources and blog posts, visit www.inquisitiveonc.comPlease find us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comArt courtesy of Taryn SilverMusic courtesy of AlisiaBeats: https://pixabay.com/users/alisiabeats-39461785/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice.Oncology for the Inquisitive Mind is recorded with the support of education grants from our foundation partners Pfizer, Gilead Pharmaceuticals and Merck Pharmaceuticals. Our partners have no editorial rights or early previews, and they have access to the episode at the same time you do. Hosted on Acast. See acast.com/privacy for more information.

In this episode, Dr Joyce O'Shaughnessy moderates a discussion with Dr Sara Hurvitz and Dr Erica Mayer answering audience questions on the latest data on incorporating CDK4/6 inhibitors into treatment plans for patients with HR+/HER2- breast cancer. Topics in this podcast include: Evidence from the monarchE and NATALEE trials of adjuvant abemaciclib and ribociclib, respectively in HR+/HER2- high-risk early breast cancerFactors used to assess risk of recurrence in early breast cancer, including the role of Ki-67 expressionDetermining the need for adjuvant chemotherapy and selection of chemotherapy agentsSelection of patients who may benefit from the addition of adjuvant CDK4/6 inhibitor therapy with endocrine therapyPotential use of preoperative CDK4/6 inhibitorsSequencing therapy for patients with high-risk early breast cancer and a germline BRCA mutationOverview of first-line therapy for advanced HR+/HER2 breast cancerExpert opinion on selection of first-line therapy and factors to considerSelection of second-line therapy based on mutational analysis and recent data from the post-MONARCH trialPresenters:Joyce O'Shaughnessy, MDCelebrating Women Chair in Breast Cancer ResearchBaylor University Medical CenterChair, Breast Disease CommitteeSarah Cannon Research InstituteTexas OncologyDallas, TexasSara A. Hurvitz, MD, FACPProfessor of MedicineHead, Division of Hematology and OncologyDepartment of Medicine, UW MedicineSenior Vice PresidentClinical Research DivisionFred Hutchinson Cancer CenterSeattle, WashingtonErica L. Mayer, MD, MPHDirector of Breast Cancer Clinical ResearchInstitute PhysicianDana-Farber Cancer InstituteAssociate Professor of MedicineHarvard Medical SchoolBoston, MassachusettsLink to full program: https://bit.ly/3XZKp8f

It is a tale as old as time, as old as the stars, the heavens and human consciousness itself. Okay, we're exaggerating a bit, but for as long as pharmacology and capitalism have been joined at the hip, the question of "which drug is best" has been at or near the forefront of medical decision-making. With the development of standardised clinical trials and the difficulty of conducting direct head-to-head comparisons, this question has become more difficult to answer conclusively. Nowhere is this epitomised better than with the triptych of available CDK4/6 inhibitors: palbociclib, ribociclib and abemaciclib. A lot of ink and pixels have been devoted to comparing the pivotal trials of these three equally pivotal agents: PALOMA-2, MONALEESA-2 and MONARCH-3, respectively. However, Josh and Michael have brought the definitive and not-at-all rambling answer to this question. Listen on to find out!Links to studies discussed in this episode (subscription may be required):Review Article (Grinshpun et al.): https://www.nature.com/articles/s41523-023-00520-7For more episodes, resources and blog posts, visit www.inquisitiveonc.comPlease find us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comArt courtesy of Taryn SilverMusic courtesy of AlisiaBeats: https://pixabay.com/users/alisiabeats-39461785/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice. Hosted on Acast. See acast.com/privacy for more information.

Dr Rugo discusses the second interim analysis of overall survival in the TROPiCS-02 trial, the implications of post-progression treatments after ribociclib and endocrine therapy in the phase 3 MONALEESA-2, MONALEESA-3, and MONALEESA-7 studies, and what the AMALEE trial indicates about optimal starting doses of first-line ribociclib in hormone receptor–positive breast cancer.

Dr. Allison Zibelli, of the Sidney Kimmel Cancer Center – Jefferson Health, and Dr. Hope Rugo, of the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, discuss the practice-changing DESTINY-Breast04 trial as well as novel therapies in metastatic HR+/HER2- breast cancer from the TROPiCS-02 and MAINTAIN studies, all of which were featured at the 2022 ASCO Annual Meeting.   TRANSCRIPT Dr. Allison Zibelli: Hello. I'm Dr. Allison Zibelli, your host for the ASCO Daily News Podcast today. I'm a vice-chair and breast medical oncologist at the Sidney Kimmel Cancer Center, Jefferson Health in Philadelphia. My guest today is Dr. Hope Rugo, 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. We'll be discussing key advances in breast cancer that were featured at the 2022 ASCO Annual Meeting. Our full disclosures are available in the show notes, and disclosures of all guests on the podcasts can be found on our transcripts at asco.org/podcasts. Hope, it's great to talk to you today. Dr. Hope Rugo: Nice to talk to you, too. Dr. Allison Zibelli: Let's begin with perhaps the most exciting abstract at ASCO this year, which was the DESTINY-Breast04 study, that's LBA3, a randomized phase 3 study of trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-low, unresectable and/or metastatic breast cancer. What are your thoughts about this study? Dr. Hope Rugo: Well, of course, this is a hugely practice-changing study as was noted in the second-to-last slide by the discussant [Dr.] Pat LoRusso. So, antibody-drug conjugates are really the next step in delivering chemotherapy to cancer cells. The antibody-drug conjugates allow targeted delivery of a toxin to the cancer cell. I think we didn't understand how important this was going to be. These second, sort of, verging on third-generation antibody-drug conjugates use an antibody approach and to then have a new generation of linkers, which allow the drug to be released locally, but to then have drugs which pack a big bang for the buck. So, the way antibody-drug conjugates are constructed, you need to have a drug that actually can't be given as a naked drug because it's too toxic because you're giving just very small amounts of this drug that are delivered directly to the cancer cell. And the other really critical part of this is that the drug-to-antibody ratio of at least the successful and new antibody-drug conjugates (ADC) is quite high in the 7.5 to 8 toxins per antibody. Now, what that's resulted in is really interesting, is that there's a bystander effect. So, the toxin itself can leak out of the cancer cell that it's targeted and kill neighboring cells, but also because of the construct of these antibody-drug conjugates, what's likely happening is even if the cancer cell's a very low expression of the target, really low, you're able to actually get that ADC into the cancer cell to kill the cancer cell. So that may be a big part of the so-called bystander effect. So trastuzumab deruxtecan is biosimilar trastuzumab linked to a topoisomerase inhibitor deruxtecan, and what happened here was that of course, we saw remarkable data in HER2+ disease, unbelievable p-values in DESTINY-Breast03 compared to T-DM1, a first-generation ADC. But in DESTINY-Breast04, we targeted a population of patients largely with hormone receptor-positive disease who had a little expression of HER2, 1 plus or 2 plus by immunohistochemistry and no gene amplification. And this trial, which randomly assigned patients 2:1 and included just 58 patients with triple-negative disease. So in this trial, 480 had hormone receptor-positive breast cancer, a median of 1 line of prior chemotherapy. They were only allowed up to 2. They were refractory to endocrine therapy, a median of 3 lines of endocrine therapy. In the overall patients and in the hormone receptor-positive patients, there was actually a doubling in progression-free survival (PFS). It started very early, and it continued throughout, and at every landmark analysis, T-DXd was better than the treatment of physician choice that patients were randomly assigned to. It's also important when you're thinking about trials like this to think about what the treatment of physician choice was, and it was all chemotherapy regimens we would use. Paclitaxel, nab-paclitaxel, capecitabine, eribulin, or gemcitabine. And, so, I think that that doesn't bring up any questions. When they looked at the hormone receptor-positive group, they saw, if anything, even a bigger benefit overall. Now, the other endpoint of this trial was overall survival, and at this first analysis, they saw an improvement in overall survival that was quite dramatic. The absolute difference was 6.4 months, which is pretty amazing for an overall survival difference. And then they looked at this exploratory endpoint at the 58 patients who were valuable at triple-negative breast cancer, and then that group of patients, also saw an improvement in PFS of 5.6 months, an improvement in overall survival of 9.9 months, very small group, but amazing data. The forest plots are exactly what you want to see, all the dots line up to the left of 1, and overall responses improved. One of the concerns with this drug has been toxicity. The toxicity showed no new toxicity signals, which is really important. Nausea is the biggest issue that we deal with. It's mostly grade 1 and 2, but still something that's important to manage. A little bit of hair loss, not much in the way of bone marrow suppression, which is interesting. Interstitial lung disease (ILD) or pneumonitis continues to be an important issue to follow. 12% of patients had ILD of any grade. Most of it was grade 1 and 2, but 3 patients died, representing 0.8%. So, this really highlights the importance of monitoring and managing pneumonitis. Regardless of that, few patients had a reduced ejection fraction, but again, very, in general, low grade. This is really a new standard of care, and the standing ovation was really due to the fact that all we do is dedicate ourselves to trying to help patients live longer and better with their cancers, and in this trial, we have a huge win that has no qualifications. We can help patients not only control their disease longer but live longer with T-Dxd compared to standard chemotherapy. Dr. Allison Zibelli: So, Hope, I know as a practicing medical oncologist, I find that our metastatic triple-negative patients are often the biggest therapeutic challenges for us. Will they be doing larger studies with these patients that are HER2-low? Dr. Hope Rugo: It's a really good point. About 65% of patients with hormone receptor-positive disease or so-called HER2-low, centrally confirmed in the study. So, a fair number of people, about a quarter, did not have HER2-low disease when they were tested centrally. In the triple-negative population, who really are ER, PR, HER2- by standard definitions, about a third of the patients might have HER2-low disease. So, there's a lot of interest in further exploring that and looking at the patients who have ultra-HER2-low disease, so between and 1 plus a little bit of expression. That's been studied in the hormone receptor-positive population in DESTINY-Breast06. But there's a lot of interesting further defining that triple-negative population, so to speak, they're going to be triple-negative plus now and understanding what the benefit is in that population. So definitely will be looked at more now moving forward. Dr. Allison Zibelli: Thank you. So, let's move on to Abstract 1002. And the results from the phase 1, 2 study of patritumab deruxtecan, a HER3-directed antibody-drug conjugate, and patients with HER3 expressing metastatic breast cancer. What are your thoughts about this study? Dr. Hope Rugo: That's a really interesting, another one of these second- to third-generation antibody-drug conjugates. It's just the antibody, instead of being the usual, sort of, HER2 or TROP2 that we're used to thinking about is directed to HER3, 1 of the HER family of proteins. This is interesting. There's actually been a lot of work trying to target HER3 with naked antibodies with disappointing results, although I have to say most of the studies really didn't push it too far. So, with this antibody drug construct, deruxtecan, which is the same as in T-DXd and another TROP2 ADC Dato-DXd is used. So, I will say they do need to change the toxin in the next generation of ADCs. But they looked at, at first did a dose-finding study which has previously been presented, and then a dose expansion in both hormone receptor-positive HER2-negative disease and triple-negative disease. All the triple-negative patients had HER3 high disease by immunohistochemistry, and the hormone-receptor-positive patients were enrolled in 2 cohorts, HER3 high and HER3 low. And the median number of prior treatment regimens that patients had received in the hormone-receptor-positive group was 6 and 2 for the triple-negative group, but there was a huge range, up to 13 lines of treatment. They only had 14 patients with HER2+ disease. So, it's a little bit hard to know what to do with that patient group, but they were heavily pretreated 5.5 prior lines of therapy. The confirmed overall response rate in the 113 patients with combined HER3 high and low was 30%, very impressive, heavily pretreated patients. For triple-negative disease all HER3 high, it was 23%. Again, very nice. And there were 14 patients with HER2+ disease that also were HER3 high. It was about 43%. So those are nice responses, but we always want to know how durable is that. The duration of response ranged from 6 to over 8 months in those 3 different groups. So, these were quite durable. It wasn't any 2- to 3-month duration of response. So very impressive. And then when they looked to see, did it matter whether you had HER3 expression that was high or low in the hormone-receptor positive group, they actually did see responses in the HER3-low group, some very good responses. Overall, there were less patients in that group, but it does suggest that maybe you would still see responses in the HER3-low group, very impressive. And then 1 really interesting correlative study they did was they looked to see what happened to the HER3 expression on the tumor cell over time, and it went down. So, you treated the HER3 expression in most of the patients just dropped off completely, which is really interesting. It didn't have any association with clinical activity, but it's sort of an interesting correlative endpoint. This is a drug that overall was pretty well tolerated. They saw a similar toxicity to T-DXd with a lot of nauseous, a little bit of alopecia, a little bit more bone marrow suppression than we're used to seeing with T-DXd. So, neutropenia was seen in about 10% of patients at the lower dose and about a quarter of the patients at the higher dose. Overall, pretty well tolerated. Now, interstitial lung disease is a toxicity with this construct, and they saw ILD of 7% but most cases were grade 1 and 2. The other interesting toxicity that's unique to this agent is thrombocytopenia. So, they saw a grade 3 or greater rate of thrombocytopenia of 27% in the lower dose group, and in the larger group that received the higher dose, 39% of grade 3 or greater thrombocytopenia, so platelets less than 100,000. Turns out that when you stop the drug, the platelets do come back, so that's a good thing. Sometimes we saw long-term thrombocytopenia with T-DM1. They didn't see bad toxicity like bleeding, but it is something that needs to be managed with this drug because we're not great at managing thrombocytopenia. In any case, it has fast-track designation for another solid tumor, not breast cancer, and we'll have to see where this fits into our dizzying array of very effective ADCs now. Dr. Allison Zibelli: The practicing medical oncologist is not used to testing for HER3 in our patients with breast cancer. How common is it? Dr. Hope Rugo: HER3 expression is quite common in hormone receptor-positive disease, a little less common in triple-negative breast cancer. So, I think that we would see expression if we were going to be treating patients with this particular approach. Dr. Allison Zibelli: All right. Let's move on to Abstract 507, which reported long-term outcomes of adjuvant denosumab in breast cancer, specifically fracture reduction and survival results from 3,425 patients in a randomized double-blind, placebo-controlled ABCSG-18 trial. What are your thoughts about this study? Dr. Hope Rugo: Well, this trial, this is an update of a study that previously has been presented and published, most recent publication was in Lancet Oncology in 2019, and these patients were randomly assigned to receive denosumab at 60 milligrams, important to note the dose, subcutaneously every 6 months versus placebo every 6 months, and they did get placebo subcutaneous injections. And this treatment continued through their endocrine therapy. They showed a dramatic reduction in fracture rate, and that has been maintained over time. We were really surprised enough to suggest that maybe Austrian people didn't go into the sun, so they got more Vitamin D deficiency, hard to know, but the hazard ratio is 0.5. It's unbelievable the number of fractures, 92 for denosumab but 176 for placebo, a P value of less than .0001. So, this is a real endpoint, treating patients who are receiving endocrine therapy that, in this case, non-steroidal aromatase inhibitor therapy that can increase bone loss, have a reduced fracture rate when they received denosumab. So that is the big take-home message, and a medium follow-up of 8 years. But the secondary endpoints included disease-free survival. They had about 20% disease-free survival events and 8% deaths, and what they saw was really interesting. So, the caveat is that 16% of patients were unblinded at the first analysis and half of them got denosumab, so it messed up their results a little bit, but the disease-free survival was significantly better in patients who received denosumab, and the hazard ratio of 0.83 and the hazard ratio does not cross 1. So that's very interesting, and even overall survival, they looked at 2 other endpoints, bone metastasis-free survival, and overall survival. They also trend towards an improvement with a hazard ratio of 0.8 for both of them. And they didn't actually see toxicity. So, patients' brittle bone fractures and osteonecrosis of the jaw (ONJ) are all concerning, but they really just did not see any risks in this patient population. I think there was 1 patient that had what they thought was a brittle bone fracture. Obviously, they watched the mouth very carefully as well. Really dramatic, and I think it's kind of disappointing that we never had any registration approach in this, and also not well-understood why the D-CARE study did not show a benefit, but I think D-CARE was designed differently. This is a better design to focus on our patients and the specific issues, and I think it's intriguing and should be considered as part of our treatment regimen for patients who are at risk for bone loss and have early-stage breast cancer on an aromatase inhibitor. Dr. Allison Zibelli: I've been using DEXA scans and offering denosumab to my patients on AIs that have osteopenia or osteoporosis. Should we be considering it in women with normal bone mass? Dr. Hope Rugo: I think not yet. Unfortunately, this trial was not immediately powered for cancer outcome, although the data are very encouraging. We don't know what the relationship is to bone loss, and providing an environment that's friendlier for cancer cells. So, do you have to have bone loss in order to have the risk that you're reducing with these agents? Certainly, that's what we've seen with zoledronate. So, I think that we don't have sufficient data to use this simply to treat cancer, but I do think that we should be considering this as an agent to give patients who have bone loss, either when you're starting an aromatase inhibitor or during the course of therapy. I think it's well tolerated, and a subcutaneous injection is not difficult. One of the questions that's come up for people is do you get bone loss that increases your risk of fracture after you stop therapy. But clearly from these updated data, these patients were off therapy. They did not have an increase of fractures and the patients treated with denosumab fared much better, I mean the hazard ratio of 0.5. Dr. Allison Zibelli: Let's move on to TROPiCS-02. That's LBA1001. This is a randomized phase 3 study of sacituzumab govitecan versus treatment of physician's choice in patients with hormone receptor-positive, HER2-negative advanced breast cancer. How do you think this study will impact practice? Dr. Hope Rugo: That's a great question. I presented this data, and I think I presented it on a Saturday, and on Sunday we saw the plenary talk of DESTINY-Breast04. These patients enrolled in TROPiCs-02 had a median number of lines of prior chemo 3 with a range of up to 8 actually, compared to a median number of lines as 1 in the DESTINY-Breast04 population. We included all hormone receptor-positive HER2 negative-advanced breast cancer, not centrally confirmed. They included just the HER2 low subset that was centrally confirmed. Everybody in our study had received prior CDK4/6 inhibitors compared to about 70% in DB04. And then 95% of patients in this trial had visceral mets. So, we did really treat a patient population who had very advanced high risk hormone receptor-positive breast cancer. As you know, we saw an improvement and progression-free survival with a hazard ratio of 0.66 meeting the endpoint. We needed a hazard ratio of 0.7, highly statistically significant P value .0003, but the median difference in PFS was only 1.5 months, and overall survival data is not yet mature. So that's brought up the question about how this drug should be used because there was a big fall off in the first 2 months where patients had rapid disease progression with heavily pretreated chemotherapy-resistant disease. We did landmark analyses and there were big separations in PFS at 6, 9, and 12 months, and 12 months, it was 21% patients free of progression and death at 1 year versus 7% for the TPC arm. So, it was a tripling of patients who were free of progression at one year. I think that's clinically relevant. This drug is associated with more neutropenia. That's the primary issue to manage, and probably half of the patients need growth factors at some point. When we looked at other endpoints response to ratio response, etc., we're better with Sacituzumab. So where does this all fit into our treatment paradigm. I think there's the HER2-low patients who will now receive T-DXd up in the, I hope, second line and not in lieu of endocrine therapy, when they're ready for chemo. But there are patients who don't have HER2-low disease and then there are patients who are going to be in the later line setting. So, I do think it still has a place in the treatment department, receptor-positive metastatic breast cancer. The results show that it was better than chemotherapy, physician choice based on our national and international guidelines, and that's better for our patients to have that option. Overall survival data obviously is looked for with great interest and that will help us put this into the right paradigm. And then I also hope that real world data will help us understand how sequential treatment with these different ADCs will benefit our patients. Dr. Allison Zibelli: This is really exciting. Do you think that we're maybe coming toward the end of conventional chemotherapy, especially for women with HER2-positive disease? Dr. Hope Rugo: I wonder if we are. I think we were interested in T-DM1 for HER2-positive disease early on. We've seen some really nice pathologic complete response data as well as adjuvant data in the attempt trial in patients who had stage I disease. Now that we have these second-, third-generation ADCs, T-DXd, I think this could potentially completely replace our chemotherapy. We still have to deal with alopecia. And I will point out ADCs are still chemotherapy. They're just a much more efficient and effective way of delivering treatment, and we need to be very careful to manage the toxicity. Dr. Allison Zibelli: Next, we're going to talk about the main pain trial that's LBA1004, which is a randomized phase 2 trial of fulvestrant or exemestane with or without ribociclib after progression on anti-estrogen therapy plus cyclin-dependent kinase 4/6 inhibition in patients with unresectable or hormone receptor-positive HER2-negative metastatic breast cancer, in other words CDK4/6 after CDK4/6. What are your takeaways here? Dr. Hope Rugo: First, just amazing that an investigator-initiated trial could do this well and be placebo-controlled. So, kudos to the principal investigator (PI) [Dr.] Kevin Kalinsky. This trial is a small phase 2 trial. A reasonable number, 119 patients were randomly assigned and evaluable patients could have received up to 1 line of prior chemotherapy for metastatic disease. If you had received prior exemestane, you received fulvestrant, if you received prior fulvestrant, you received exemestane, and actually if you looked at the number of patients who had received fulvestrant, it was 99 versus only 20 with exemestane. So important to keep in mind. If you looked at the overall population where the primary endpoint was progression-free survival, the hazard ratio is 0.57, just median PFS of 2.8 months in patients receiving endocrine therapy and placebo and 5.3 months for patients receiving endocrine therapy and ribociclib. So was this ribociclib after ribociclib or ribociclib after something else. 86% of patients had received palbociclib as their prior CDK4/6 inhibitor, and only about 10% to 14% had received prior ribociclib. So, there's a predominance of palbociclib followed by ribociclib. The other thing that's important to keep in mind is how sick this patient population was. Very few had received prior chemotherapy in the less than 10% range, visceral metastases in about 60%. So that's helpful. Only 19% or so had received 2 or more endocrine therapies from metastases. So, most people did this as their second line treatment. The PFS, when you looked at fulvestrant or exemestane, looked like the benefit was relatively similar, but you know you got 20 patients in the exemestane arm. The hazard ratios, looking at the subgroup analyses, all looked pretty similar, and the overall response and clinical benefit rate were better with continuing the cyclin dependent kinases (CDK) inhibitor. There was interesting sub-analysis looking at mutations and how that affected things. And they looked at patients who had ESR1 mutations or had wild-type ESR1. 42% had ESR1 mutations at study entry, very similar to what we've seen. In that group of patients, remember it's only 33 where they had this analysis, they saw a lot of other mutations. So p53, PIK3CA, FGFR, CCND1—those patients did not benefit. Only 33 patients. No benefit at all, very short PFS, about 3 months. The patients who had ESR1 wild type seemed to benefit a lot, 45 patients going from about 3 months to a little over 8 months. So, this is all hypothesis-generating data. I wouldn't run out and use this as your standard of care now because it is small data. But when the patient doesn't have other good options, I certainly would consider switching the CDK and going on, add that to the next line endocrine therapy. It's important to switch the endocrine therapy. I think we really need to look at the ongoing phase 3 trials to give us better evidence basis and understand the impact of mutations and prior therapy on who might benefit from continued CDK inhibitors after progression on a CDK inhibitor. Dr. Allison Zibelli: I think this is a really exciting trial. We all have a lot of patients on palbociclib and letrozole who've been on for 4, 5 years, and would like to continue with this kind of treatment because the side effects are really manageable. So, I look forward to seeing what's coming in the future with the phase 3 trials. So, let's talk about Abstract 1015, which I thought is a great idea. It looks at the quality of life with ribociclib plus aromatase inhibitor versus abemaciclib plus AI as first-line treatment of hormone receptor-positive, HER2-negative advanced breast cancer, assessed via matching adjusted indirect comparison. Could you tell us what matching adjusted indirect comparison is and why you chose this for the study? Dr. Hope Rugo: It's an interesting question. How do you compare across trials? So, matching this kind of make analysis, we'll call it a make analysis for the purposes of this discussion, allows you to match patients and weight based on their characteristics that might affect patient reported outcomes. And that actually is a way of trying to do a fair cross-trial comparison. So basically, take the study population, you match the inclusion and exclusion criteria, and then you weigh the different criteria so that you can try and make a better association. It's the best way we know of comparing across trials. You know, a lot of people ask why we didn't have PALOMA-2 in here, and that's because they used a different patient reported outcome tool. So, you have to use the same patient reported outcome tool in order to compare. So that's why we did this analysis, and it sort of came on the heels of a survey that Fatima Cardoso presented at San Antonio in 2021, where patients identified diarrhea as a symptom they really didn't like more than everything else. And you can imagine, I think we all have that experience in practice, the unexpected nature of diarrhea and the fact that it does limit your activities and, therefore, quality of life are important. In this analysis, interestingly but not surprisingly, ribociclib favored abemaciclib in diarrhea, and there can be associated appetite loss, so ribociclib also favored abemaciclib for appetite loss. And I thought the last one was interesting—fatigue—because I wouldn't have assumed that fatigue would be different. And maybe it's associated with diarrhea. They have these funny arm symptoms that were better. We don't really know why that was, and it's hard to assess again. We're really not clear based on the differences between the drugs. So, there are limitations to the analysis, but I think that it helps us really in individual patients try and match patients' underlying symptoms with the best treatment to offer them the best quality of life as they're being treated in the metastatic setting. Dr. Allison Zibelli: I thought this study was great because it really centered the experience of the patient and the wishes of the patient. You don't see that designed into many clinical trials, the way this was. So, I thought that was a great feature of this study. Dr. Hope Rugo: I will say that all of the 3 studies that looked at CDK inhibitors, all those 3 studies included patient-reported outcomes. That's an important new approach that is really being focused on. Dr. Allison Zibelli: Do you consider the CDK4/6 inhibitors equivalent in efficacy, and could you substitute them to try to get the side effect profile that you want? Dr. Hope Rugo: Well, I think that we saw in the early stage setting that there are differences. Now, across the different trials, there are big differences in patient populations and inclusions as we saw in the PALOMA-2 results that were presented at ASCO [Annual Meeting], whether the patients had prior chemotherapy like in PALOMA-3, whether they had a short disease-free interval, the higher risk patients in PALOMA-2. The PALOMA trials were more broadly inclusive than the other 2 studies, the MONALEESA and MONARCH series of trials. So, we do have to be a little bit careful about comparing apples to oranges, but we have the early-stage results of MONARCH E showing a clinically important difference in outcome whereas the PALLAS and Penelope-B trials didn't. So that sort of puts us into a little bit of a question period. Are these all patient populations or are there differences between the agents? The PFS and the metastatic setting, all the hazard ratios line up. So, in truth, although I know the activity against cyclin-independent kinases are different between agents, we don't still really understand the clinical differences in efficacy, but I think we all are practicing using evidence-based medicine. I wouldn't, for example, substitute a different CDK4/6 inhibitor for abemaciclib in the treatment of early-stage breast cancer. We have to just learn how to manage the diarrhea and use prophylaxis and dose reduce early to manage this and make it tolerable for our patients. And in the metastatic setting, I think we need to follow evidence-based guidelines and use the best data available to decide on the right treatment approach and sequencing for our patients. Dr. Allison Zibelli: Thank you, Hope, for coming on the podcast today. This was a really interesting review of one of the most exciting ASCO [Annual Meetings] I've been to. And thanks for sharing your valuable insights with us and helping us make sense of all this really new exciting data. We really appreciate it. Dr. Hope Rugo: Thank you. And thank you so much for inviting me. Dr. Allison Zibelli: And thank you to our listeners for joining us today. You will find the links to all the abstracts discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. That really helps other listeners find us. Thank you.   Disclosures: Dr. Allison Zibelli: None disclosed. Dr. Hope Rugo: Honoraria: Puma Biotechnology, Mylan, Samsung Bioepis, Chugai Pharma, Blueprint Medicines Consulting or Advisory Role: Napo Pharmaceuticals Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Genentech, Merck, Odonate Therapeutics, Daiichi Sankyo, Sermonix Pharmaceuticals, AstraZeneca, Gilead Sciences, Ayala Pharmaceuticals, Astellas Pharma, Seattle Genetics, Macrogenics, Boehringer Ingelheim, Polyphor 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. 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.

Dr. Allison Zibelli, of the Sidney Kimmel Cancer Center – Jefferson Health, highlights key advances from the EMBER study and promising data on QOL for HR+/HER2- patients taking checkpoint inhibitors featured at the 2022 ASCO Annual Meeting.   Transcript:  ASCO Daily News: Hello and welcome to the ASCO Daily News Podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. My guest today is Dr. Allison Zibelli, a breast medical oncologist and assistant professor of medicine at the Sidney Kimmel Cancer Center Jefferson Health.  Dr. Zibelli will highlight key posters on breast cancer that will be featured at the 2022 ASCO Annual Meeting. Dr. Zibelli's full disclosures are available in our show notes, and disclosures of all guests on the podcast can be found on our transcripts at asco.org/podcasts.  Dr. Zibelli, it's great to have you on the podcast today.  Dr. Allison Zibelli: Thank you. It's nice to be here.  ASCO Daily News: Let's begin with Abstract 1021 and the “Phase 1 EMBER Study.” Can you tell us why this study should be on our radar?  Dr. Allison Zibelli: This study was very interesting because it's testing a novel therapy, which is imlunestrant, an orally bioavailable SERD, or a selective estrogen receptor degrader. This drug is for patients with ER-positive, HER2-negative advanced breast cancer. And they're presenting updated data from the dose-escalation phase and the dose-expansion phase of the EMBER trial.  This trial enrolled 138 patients at a median age of 62 years. The median number of prior therapies for these women was 2. The adverse events were low. They could have prior platinum therapy but no prior fulvestrant or aromatase inhibitor. The premenopausal women in the study received concomitant GnRH antagonist. They had substantial clinical benefit with this therapy with no dose-limiting toxicities.  It had a favorable side effect profile with no cardiac or ophthalmic safety signals, and it had excellent efficacy in patients with heavily pretreated ER-positive advanced breast cancer. This is the first study showing efficacy and safety with an oral SERD. And we're all looking for new oral, well-tolerated therapies for our patients with metastatic estrogen receptor-positive breast cancer.  These patients were heavily pretreated, and they had a median of 2 prior therapies. Most of the patients with advanced breast cancer had prior endocrine therapy, 92% had a prior CDK 4/6 inhibitor, 50% had fulvestrant, and 26% had chemotherapy.  Despite this, they had an overall response rate of 5% with a clinical benefit rate of 47%. So, it'll be very interesting for us to see what happens with this new class of SERDs in the future.  ASCO Daily News: Excellent! So, moving on to Abstract 514. This study addressed patients with high-risk early breast cancer who received pembrolizumab within the new adjuvant biomarker rich I-SPY 2 trial. Can you tell us more about this study?  Dr. Allison Zibelli: This is a very interesting study, which is a platform study comparing various investigational treatments to a standard therapy which was ACT, with or without herceptin, depending on the HER2 status of the patient versus an experimental agent.  One arm of the I-SPY study was neoadjuvant pembrolizumab. This paper is very interesting to me because it's hard to know in advance who will respond to immune checkpoint inhibitors. And that's what this study was designed to answer.  So, they took 69 patients who were on the I-SPY study, they all had high-risk MammaPrint scores, and all of them were HER2 negative, and with these patients, they had 31 complete responses to neoadjuvant pembrolizumab and 38 patients with a residual disease after neoadjuvant pembrolizumab. Notably, of the 31 complete responses, 12 were ER-positive, and 19 were triple-negative.  In the residual disease patients, 28 were ER-positive and 10 were triple-negative. If you compare this with historical data, the response rate for pembrolizumab is about 20% for patients who are triple-negative and about 12% for patients who are ER-positive.  So, the response rates that they had were higher in general. So, what the study did was they found a signature of 53 genes which they named imprint, which was identified with a greater than 90% sensitivity and greater than 80% specificity for predicting complete response to pembrolizumab in all patients.  This worked equally well for the patients who are estrogen receptor-negative and estrogen receptor-positive. In KEYNOTE-086 cohort B, which was presented at the American Association for Cancer Research Annual Meeting (AACR), PD-L1 of greater than 1% only predicted a 23% response rate to pembrolizumab.  So, if we could use the imprint study to predict patients who would respond to pembrolizumab, it would save a lot of needless toxicity and a lot of needless expense, in treating the patients who would have benefit.  So, this is going to be a very useful method to identify patients that we want to treat with pembrolizumab, and perhaps other immune checkpoint inhibitors as well. I think this might be the next “Oncotype” as it were, in that it will be able to predict who will benefit from a specific therapy.  ASCO Daily News: Thank you! Let's move on to Abstract 519. This is a randomized pre-surgical trial of alternative dosing of exemestane in postmenopausal women with early ER-positive breast cancer. What are your key takeaways here?  Dr. Allison Zibelli: I thought this was a great design of a study. It was a window of opportunity for the test. So, what they did was, they tested 3 different dosing schedules of exemestane in patients waiting for surgery for ER-receptor-positive breast cancer.  The patients were randomly assigned to either receive exemestane 20 milligrams a day, the standard schedule, 25 milligrams 3 times a week, or 25 milligrams once a week for 4 to 6 weeks prior to surgery.  Their endpoint was percent decrease in circulating estradiol and what they found was the 3 times a week schedule was comparable to the daily schedule. The once-a-week schedule didn't seem to be adequate to decrease estradiol, but 3 times a week was equivalent to daily.  This was really interesting because we know that our patients have difficulty tolerating aromatase inhibitors. We know from formal studies that about 25% of patients discontinue aromatase inhibitors prematurely because of side effects. Small studies in actual practice settings show it's probably even higher than that—between 30 and 50% of patients discontinue aromatase inhibitors.  So, for the patient that can't tolerate daily therapy, 3 times a week therapy is an attractive option, that may be just as good as daily. I think it is very important for patients who have to take these drugs for years that they have a way to take them that is tolerable.  ASCO Daily News: Absolutely. Well, the last study I'd like to ask you about is Abstract 1015. This looks at the quality of life for patients with HR-positive, HER2 negative advanced breast cancer. So, what does this study tell us about quality of life with different CDK 4/6 inhibitors?  Dr. Allison Zibelli: So, we have a lot of studies of CDK 4/6 inhibitors. And we know that they dramatically improve the overall survival of women with ER-positive metastatic breast cancer. What we also know is that they have a lot of side effects. And for women that have to take these drugs for years, that's important.  So, this study was a matching adjusted indirect comparison study. This is a method that uses individual patient data to create balanced trial populations across separate studies, and they use patients from the MONALEESA-2 trial, which was ribociclib plus AI, compared to MONARCH 3, which used abemaciclib plus AI, the endpoint was something they called “time to sustain deterioration,” which was a decrease in 10 points in the quality of life score, they use the QLQ-C30 questionnaire. The upshot of their data was that ribociclib was more tolerable, mostly with less appetite loss, less diarrhea, and less fatigue than abemaciclib.  So, this is 1 of the first studies we've seen that directly compares, well sort of directly compares the quality of life between these 2 drugs, and this may be a data point that favors ribociclib.  ASCO Daily News: Well, thank you, Dr. Zibelli, for highlighting some really important advances in breast cancer that will be featured at the 2022 ASCO Annual Meeting. We really appreciate it.  Dr. Allison Zibelli: Thank you very much for having me.  ASCO Daily News: And thank you to our listeners for joining us today. If you're enjoying the content on the ASCO Daily News podcast. Please take a moment to rate review and subscribe wherever you get your podcasts.  Disclosures:   Dr. Allison Zibelli: None disclosed.  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. 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.     

On this episode, we'll be discussing an updated overall survival analysis from the MONALEESA-3 trial presented at the ESMO Breast Cancer Congress 2022. Then, we'll hear from a researcher about the current state of cancer research and anticipated trends in the field.Coverage of stories discussed this week on ascopost.com:Updated Overall Survival Results From MONALEESA-3 Show Improved Overall Survival in Patients With HR-Positive/HER2-Negative Breast CancerTo listen to more podcasts from ASCO, visit asco.org/podcasts.

In this week's episode, we'll discuss a recent FDA approval in germline BRCA-mutated, HER2-negative, high-risk early breast cancer. Then, we'll hear about the publication of final overall survival results from the MONALEESA-2 trial, which evaluated the efficacy of the addition of ribociclib to letrozole in the first-line treatment of postmenopausal women with hormone receptor–positive, HER2-negative advanced breast cancer.Coverage of stories discussed this week on ascopost.com:FDA Approves Olaparib for Adjuvant Treatment of High-Risk Early Breast CancerFinal Overall Survival Analysis of MONALEESA-2: Addition of Ribociclib to Letrozole in Postmenopausal Women With HR-Positive, HER2-Negative Advanced Breast CancerTo listen to more podcasts from ASCO, visit asco.org/podcasts.

According to The American Cancer Society, Metastatic breast cancer (mBC) is the most serious form of the disease and takes a life in the United States approximately every 12 minutes creating an urgent need for treatment proven to extend life while preserving quality of life. My guests, Dr. Denise A. Yardley, a MONALEESA-2 Investigator, Breast Cancer Research Program, Sarah Cannon Research Institute and Shirley A. Mertz, President, Metastatic Breast Cancer Network, join me with the updated results of a targeted treatment  from the Monaleesa-2 trial.

According to The American Cancer Society, Metastatic breast cancer (mBC) is the most serious form of the disease and takes a life in the United States approximately every 12 minutes creating an urgent need for treatment proven to extend life while preserving quality of life. My guests, Dr. Denise A. Yardley, a MONALEESA-2 Investigator, Breast Cancer Research Program, Sarah Cannon Research Institute and Shirley A. Mertz, President, Metastatic Breast Cancer Network, join me with the updated results of a targeted treatment  from the Monaleesa-2 trial.

Koos van der Hoeven bespreekt met Agnes Jager de resultaten van de KEYNOTE-522-studie, DESTINY-Breast03-studie, Tulip SYD985-studie en de MONALEESA-2-studie gepresenteerd op het ESMO Congress 2021.

Dr. Gabriel Hortobagyi is professor of breast medical oncology at the University of Texas MD Anderson Cancer Center. He is a past president of the American Society of Clinical Oncology and is one of the world's leading authorities on breast cancer treatment. He has published more than 1,000 papers in peer-reviewed journals. At the European Society for Medical Oncology Congress 2021, Dr. Hortobagyi presented overall survival results from the MONALEESA-2 trial, which compared the combination of Kisqali and Femara to Femara alone to treat advanced-stage hormone-receptor-positive HER2-negative breast cancer in postmenopausal women. Earlier results from the study found that adding Kisqali to Femara improved progression-free survival — the amount of time the women lived without the cancer growing. These new results found that the combination of Kisqali and Femara also improved overall survival — the length of time women lived whether the cancer grew or not. Listen to the episode to hear Dr. Hortobagyi explain: the goals of the MONALEESA-2 study why the overall survival difference of more than 1 year is so important whether the improvement in overall survival is likely to be the same no matter which aromatase inhibitor is used what the results mean for postmenopausal women diagnosed with advanced-stage hormone-receptor-positive HER2-negative breast cancer

El Dr. Fernando Aldaco, oncólogo médico adscrito al Centro Médico Nacional "20 de Noviembre" ISSSTE en la Ciudad de México, México, junto con el Dr. Henry Gómez, oncólogo médico del Instituto Nacional de Enfermedades Neoplásicas en Lima, Perú, nos comentan sobre lo más destacado en cáncer de mama, presentado en el Congreso Anual de la Sociedad Europea de Oncología Médica, resaltando los siguientes estudios: Estudio del Gruppo Italiano Mammella: Estudio fase III, prospectivo, abierto, con pacientes con cáncer de mama en estadio I-III, sin recurrencia después de 2-3 años de tamoxifeno, las cuales fueron asignadas al azar (1:1) a recibir 2-3 años (brazo de control) o 5 años (brazo extendido) de letrozol. DESTINY-Breast03: Estudio fase III, multicéntrico, aleatorizado (1:1), que compara la eficacia y seguridad de trastuzumab deruxtecan vs. trastuzumab emtansina en pacientes con cáncer de mama metastásico HER2+ previamente tratadas con trastuzumab y taxanos. MONALEESA-2: Se presentó el análisis final de los resultados de supervivencia global del estudio de ribociclib + letrozol. Este es un ensayo fase III, doble ciego, controlado con placebo, que aleatorizó (1:1) a mujeres posmenopáusicas con cáncer de mama avanzado RH+/HER2-, no tratadas para enfermedad avanzada. Metaanálisis que incluyó los estudios CALGB40601, CHER-LOB, NSABP-B41, NeoALTTO: Evaluó la supervivencia de pacientes con cáncer de mama temprano HER2+ que recibieron terapia neoadyuvante con trastuzumab y lapatinib o trastuzumab solo y quimioterapia. KEYNOTE 355: Resultados finales del estudio fase III, aleatorizado (2:1), doble ciego, que evaluó pembrolizumab + quimioterapia vs. placebo + quimioterapia en pacientes con cáncer de mama triple negativo metastásico o inoperable sin tratamiento previo y localmente recurrente.

En este podcast, la Dra. Isabel Enríquez, oncólogo médico adscrita al Servicio de Oncología Médica del H.R. ISSSTE León, en León, Guanajuato, nos comenta algunoshighlights del día 4 de ESMO 2021: Cáncer de mama: · KEYNOTE 355: Estudio fase III, aleatorizado, doble ciego que evaluó pembrolizumab + quimioterapia vs. placebo + quimioterapia, se evaluó a 882 pacientes con cáncer de mama triple negativo metastásico o inoperable sin tratamiento previo localmente recurrente. · MONALEESA-2: Estudio fase III, aleatorizado, doble ciego, controlado con placebo de ribociclib + letrozol, donde se evaluó a 668 mujeres posmenopáusicas con cáncer de mama avanzado RH+ , HER2 negativo y que no habían recibido tratamiento para la enfermedad avanzada. · TULIP: Estudio fase III, multicéntrico, aleatorizado, de etiqueta abierta que evaluó a 436 pacientes, se comparó la eficacia y seguridad de trastuzumab duocarmazina (SYD985) vs. el tratamiento elegido por el médico hasta la progresión de la enfermedad o toxicidad inaceptable, pacientes con cáncer de mama metastásico o localmente avanzado irresecable HER2+. Tumores genitourinarios: · STAR: Estudio fase II/III, multicéntrico, aleatorizado que evaluó a pacientes con carcinoma de células renales metastásico, los cuales fueron tratados con sunitinib/pazopanib. · STAMPEDE: Estudio fase II/III, aleatorizado, de etiqueta abierta, de múltiples brazos y etapas, el cual evalúa la eficacia de distintos fármacos como terapia sistémica para pacientes con cáncer de próstata avanzado o metastásico M0, estos fueron tratados con terapia de privación androgénica vs. abiraterona + prednisolona con o sin enzalutamida. · PEACE 1: Estudio fase III, aleatorizado, de etiqueta abierta, de asignación paralela, en donde se utilizó la terapia de privación de andrógenos con o sin docetaxel, radioterapia local, acetato de abiraterona y prednisona en pacientes con cáncer de próstata metastásico sensible a la castración sin tratamiento previo. Cáncer de pulmón de células no pequeñas: · EMPOWER-Lung3: Estudio fase III, aleatorizado, doble ciego que evaluó las combinaciones de cemiplimab (anticuerpo anti-PD-1) + quimioterapia basada en platino vs. placebo + quimioterapia para el tratamiento de 1L en pacientes con cáncer de pulmón de células no pequeñas avanzado o metastásico.

La Dra. Claudia Arce, oncólogo médico adscrita al Instituto Nacional de Cancerología en la Ciudad de México, México, junto con el Dr. Iván Bustillo, oncólogo clínico de la Clínica Portoazul en Barranquilla, Colombia, nos comparten un resumen sobre los estudios de cáncer de mama presentados durante el pasado Congreso de ASCO 2021. Cáncer de mama temprano: WSG-ADAPT-HR-/HER2+: Ensayo prospectivo, multicéntrico, fase II, de pertuzumab neoadyuvante desescalado más trastuzumab con o sin paclitaxel semanalmente en cáncer de mama temprano, HR-/HER2+. ECOG-ACRIN 5103: Estudio para evaluar si las citocinas y/o quimiocinas inflamatorias pueden estar asociadas con la recurrencia a distancia del cáncer de mama temprano, HER2–. OlympiA: Estudio fase III, multicéntrico, aleatorizado y controlado con placebo de olaparib adyuvante después de quimioterapia neo/adyuvante en pacientes con mutaciones de la línea germinal BRCA1/2 y cáncer de mama temprano, HER2– de alto riesgo. Cáncer de mama avanzado: MONALEESA-3: Resultados actualizados de supervivencia global del estudio fase III, que asignó aleatoriamente (2:1) a pacientes posmenopáusicas con cáncer de mama avanzado, HR+/HER2–, a recibir fulvestrant ± ribociclib. PALOMA-3: Actualización de la supervivencia global de palbociclib más fulvestrant en pacientes con cáncer de mama avanzado HR+/HER2–. Este fue un estudio fase III, aleatorizado, doble ciego, controlado con placebo. Cáncer de mama triple negativo: EA1131: Ensayo posoperatorio, aleatorizado, fase III, de no inferioridad (con alternativa de superioridad) que evaluó el uso de quimioterapia a base de platino vs. capecitabina en pacientes con cáncer de mama residual triple negativo después de quimioterapia neoadyuvante. FUTURE-C-PLUS: Un estudio prospectivo, fase II, de un solo brazo, que evaluó la combinación de famitinib con camrelizumab más nab-paclitaxel como tratamiento de primera línea para pacientes con cáncer de mama inmunomodulador avanzado triple negativo. ASCENT: Estudio fase III, que evaluó sacituzumab govitecan en pacientes con cáncer de mama metastásico triple negativo que recibieron quimioterapia neo/adyuvante. También, se informan resultados en pacientes de 65 años o más.

La Dra. Marinee Torres, oncólogo médico, adscrita al servicio de oncología del Cancun Cancer Institute, en Quintana Roo, nos habla brevemente sobre los highlights del día 3 del Congreso ASCO 2021: Cáncer de mama: Resultados de ECOG-ACRIN EA1131, un estudio posoperatorio, aleatorizado, fase III, de quimioterapia a base de platino vs. capecitabina en pacientes con cáncer de mama triple negativo residual, después de quimioterapia neoadyuvante. Resultados a más de 6 años de PALOMA-3, un análisis de supervivencia global de palbociclib más fulvestrant en pacientes con cáncer de mama avanzado, RH+/HER2- vs. fulvestrant solo. Resultados de SG actualizados a 5 años del estudio MONALEESA-3, de fulvestrant y ribociclib vs. fulvestrant solo en pacientes posmenopáusicas con cáncer de mama avanzado, RH+/HER2-. Resultados del estudio FUTURE-C-PLUS, prospectivo, fase II, de un solo brazo (famitinib en combinación con camrelizumab más nab-paclitaxel), para el tratamiento de pacientes con cáncer de mama triple negativo inmunomodulado avanzado, en primera línea. Melanoma: Resultados del crossover y rechallenge de la colaboración entre el EORTC 1325 y el KEYNOTE-054 de pembrolizumab en pacientes con melanoma en estadio lll de alto riesgo con resección completa. Los pacientes fueron aleatorizados a recibir pembrolizumab o placebo cada 3 semanas por un año y tras recurrencia, sin metástasis cerebrales, los pacientes con ECOG PS 0-2 fueron elegibles para ingresar a la parte 2 del estudio y recibir pembrolizumab durante máximo 2 años. Mieloma múltiple: Resultados actualizados del estudio KarMMa con idecabtagene vicleucel, una terapia CAR-T dirigida contra BCMA, para el tratamiento del mieloma múltiple en recaída o refractario.

The PENELOPE-B phase III trial did not show a benefit to the addition of one year of the CDK4/6 inhibitor palbociclib to adjuvant endocrine therapy in patients with hormone receptor-positive/HER2-negative breast cancer and residual disease after neoadjuvant chemotherapy.   TRANSCRIPT This JCO podcast provides observations and commentary on the JCO article “Palbociclib for Residual High-Risk Invasive Hormone Receptor-positive, HER2 negative Early Breast Cancer – The PENELOPE-B Trial,” by Sybille Loibl and colleagues. My name is Erica Mayer, and I am a clinical investigator at the Dana-Farber Cancer Institute in Boston, MA who specializes in breast cancer. Since the initial approval of the CDK4/6 inhibitor palbociclib in 2015, this class of agents has become a standard part of management for most patients with hormone receptor positive HER2 negative advanced breast cancer. Use of one of the available CDK4/6 inhibitors - palbociclib, abemaciclib, or ribociclib - in combination with endocrine therapy, improves progression-free, and even overall survival, in the advanced disease setting, as shown in the respective trial series PALOMA, MONARCH, or MONALEESA. Although differentiated by their toxicity profiles, with palbociclib and ribociclib contributing more neutropenia and abemaciclib more diarrhea, across-the-board the benefit gained from use of these agents is remarkably preserved between trials, without apparent differential drug activity. Following the observation of benefit from use of CDK 4/6 inhibitors in the advanced setting, clinical trials evaluating the three available agents were subsequently launched to evaluate these agents in the adjuvant setting, after prior treatment with surgery, chemotherapy, and radiation if necessary. The first two trials to report in 2020, PALLAS and MONARCH-E, enrolled patients with early hormone receptor positive HER2- breast cancer, randomizing them to receive a CDK 4/6 inhibitor, palbociclib or abemaciclib respectively, for a planned 2-year duration, in addition to ongoing adjuvant endocrine therapy, versus ongoing adjuvant endocrine therapy alone. Notably, PALLAS enrolled patients with stage II and III breast cancer, whereas MONARCH-E targeted a high-risk group identified by tumor size, nodes, and Ki67 status. Initial reports from these trials were presented at an interim follow-up of about 20-24 months, a time when many were still receiving the combination therapy. The MONARCH-E analysis demonstrated a benefit from the addition of abemaciclib to endocrine therapy in prolonging invasive disease-free survival. This benefit was not observed with the addition of palbociclib in the PALLAS trial. The ongoing NATALEE trial, offering 3-years of reduced dose ribociclib in a similar setting, continues accrual. It is within this context that we place the PENELOPE-B trial. This trial enrolled the highest risk patients with early HR+/HER2- breast cancer: those with residual disease after preoperative chemotherapy and a high CPS-EG score, which is a calculation of anatomic stage and tumor biology meant to identify patients at highest risk of cancer recurrence. A total of 1250 patients were randomized to receive either one year of adjuvant palbociclib with ongoing adjuvant endocrine therapy, or placebo with endocrine therapy, and followed for a primary endpoint of invasive disease-free survival.  As expected, the study enrolled a very high-risk population, with many patients having at least T2 disease and 4 involved lymph nodes at time of surgery. At a median follow-up of 43 months, no difference in invasive disease-free survival was observed, with a 4-year iDFS of 73% in the intervention arm, versus 72.4% in the placebo arm. No clinicopathologic subgroup appeared to derive benefit from the research intervention. The toxicity experience was similar to that seen in the metastatic setting, with notable and expected hematologic toxicity, but no significant difference in overall non-hematologic adverse events. Overall, drug exposure was satisfactory, with about 17% of patients unable to complete the planned 1-year duration of therapy. The PENELOPE-B study makes its mark in the adjuvant CDK4/6 landscape in several important ways. First, PENELOPE-B has the greatest duration of follow-up, allowing analysis of mature data and outcomes during and following adjuvant CDK4/6 inhibition. Although it is tempting to interpret a slight visual divergence of the Kaplan Meyer curves during the palbociclib exposure, where there is an absolute difference in iDFS of 4.3% at 2 years, there is no statistical evidence that the 2-year iDFS estimates are different between the two arms, and therefore no evidence of time-dependent efficacy. Importantly, in regard to experiences within the other CDK4/6 inhibitor trials, which have reported at an earlier time point, longer-term follow-up of those trials will be necessary to determine stability and maturity of the observed results. Additionally, PENELOPE-B is the only placebo-controlled trial presented to date. For that reason, the toxicity data presented represents the purest description of the experience of receiving a CDK4/6 inhibitor in the adjuvant setting in a population with prior chemotherapy exposure. Finally, when discriminating among the CDK4/6 inhibitors study populations, it is important to remember that PENELOPE-B enrolled a population of greatest established risk, suggesting any apparent differential outcome among the trials is unlikely related to differing baseline risk of accrued patients. Overall, PENELOPE-B represents a significant contribution to the breast cancer field, and substantially adds depth and dimension to the exploration of CDK4/6 inhibitors in the adjuvant setting. At the time of publication, it is unclear if an approved role will emerge for a CDK4/6 inhibitor in adjuvant therapy for our early breast cancer patients. Many questions remain regarding patient/tumor selection, agent differentiation, duration of therapy, and potential biomarkers. Importantly, the correlative analyses planned for all of the CDK4/6 inhibitor trials and molecular exploration of patient samples will substantially improve our understanding of the impact of these drugs in the early setting, and our overall ability to treat this subset of breast cancer. While waiting for these data, we should continue our focus on providing the best possible care for our patients with hormone receptor-positive, HER2-negative breast cancer who are being treated with endocrine therapy. This concludes this JCO podcast. Thank you for listening.

Dr. Rafael Kaliks, autor do MOC, comenta os trabalhos de maior relevância em câncer de mama apresentados na ESMO 2019. Dentre, os estudos Keynote 522, TAILOR X, MONARCH 2, MONALEESA-3 e KEYNOTE 119.

El Dr. Efraín Alarcón nos comparte las actualidades en cáncer de mama avanzado HR+ HER2- presentadas en ESMO 2019 con dos estudios de gran relevancia como son el MONARCH 2 y MONALEESA 3.

This week, we'll be discussing selected breast cancer abstracts presented at the ESMO Congress 2019, including the MONALEESA-3 and MONARCH-2 studies of CDK4/6 inhibitors for advanced breast cancer; the BROCADE 3 trial of veliparib plus carboplatin and paclitaxel in some advanced BRCA-mutated breast cancers; and the KATE-2 study of atezolizumab and trastuzumab emtansine in HER2-positive breast cancer.Coverage of stories discussed this week on ascopost.com:ESMO 2019: BROCADE 3: Veliparib Plus Carboplatin/Paclitaxel in Patients With HER2-Negative, Germline BRCA-Mutated Advanced Breast Cancer

Dr. Marcio Debiasi, autor do MOC, comenta sobre a esperada atualização do estudo MONALEESA-7, que teve os resultados de sobrevida livre de progressão apresentados na ASCO 2018, e agora trouxe os resultados de sobrevida global.

Dr. Antonio Carlos Buzaid comenta os resultados do MONALEESA-7, apresentados na ASCO 2019, estabelecendo o padrão ouro na primeira linha do câncer de mama metastático RH positivo, HER-2 negativo.

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.

Dr. Evandro de Azambuja, do Institut Jules Bordet, na Bélgica, fala sobre as novidades em câncer de mama apresentadas na ASCO 2019, dando destaque aos estudos MONALEESA-7, CLEOPATRA e mais dois estudos que observaram aspectos relacionados a survivorship.

El Dr. Diego Lucas Kaen nos hace un recuento del MONALEESA-7 presentado en ASCO 2019.

This week, we discuss an interim analysis of the MONALEESA-7 trial of the addition of ribociclib to endocrine therapy in pre- or perimenopausal women with advanced hormone receptor–positive, HER2-negative breast cancer. We also talk about a study that examined the relationship between the duration of chemotherapy and body mass index and the development of lymphedema in some patients with breast cancer. Lastly, we present three recent approvals and regulatory communications from the FDA.Coverage of stories discussed this week on ascopost.com:Overall Survival With the Addition of Ribociclib to Endocrine Therapy in Advanced HR-Positive, HER2-Negative Breast CancerNeoadjuvant Chemotherapy Duration and Obesity May Be Associated With Increased Risk of Lymphedema in Some Women With Breast CancerFDA Approves Rituximab Biosimilar for Non-Hodgkin Lymphoma, CLL, and Autoimmune ConditionsFDA Requests Manufacturer Recall of Some Textured Breast ImplantsFDA Approves Pembrolizumab for Some Patients With PD-L1–Positive Esophageal Cancer

This week we begin the episode by discussing MONALEESA-7 and why ribociclib has been shown to increase overall survival while palbociclib has not. We finish the episode with an in-depth interview with Dr. Stacie Dusetzina of Vanderbilt University on her work in pharmacoeconomics, specifically we discuss her work on the market value of cancer drugs. MONALEESA-7: doi.org/10.1056/NEJMoa1903765 Free drug samples are a marketing tool: doi.org/10.2105/AJPH.2007.114249 Back us on Patreon! www.patreon.com/plenarysession

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.

BARCELONA—More pre-menopausal women who have estrogen receptor (ER) positive advanced breast cancer could be spared chemotherapy—according to latest findings from the MONALEESA-7 double-blind randomized phase 3 trial in which either placebo (PBO) or the cyclin-dependent kinase (CDK) 4/6 inhibitor ribociclib …Nadia Harbeck with Emiel Rutgers AJO PRODUCTION MASTER

Dr Gnant talks to ecancertv at ESMO 2016 about the results of the MONALEESA-2 and PALOMA-2 trials, which confirm, he says, that the addition of cell cycle inhibitors (specifically, CDK4/6) can be of great benefit to patients with metastatic breast cancer. He discusses the results of both trials with particular regards to toxicity.

Prof Richard Finn (University of California, Los Angeles, USA) chairs an expert discussion on the latest in CDK inhibition in breast cancer for ecancertv at SABCS 2016 in San Antonio with Professor Michael Gnant (Medizinischen Universität Wien, Vienna, Austria), Dr Mark Harries (Guy’s & St Thomas’ Hospitals NHS Foundation Trust, UK) and Prof Sandra Swain (Georgetown University Medical Center, Washington, DC, USA) 15 years after the Nobel Prize in Physiology was awarded for the identification of the role of CDK in regulating the cell cycle, 2016 has seen some of the most exciting advances for the actual and potential clinical utility of this research for breast cancer patients. The panel first discussed Phase III data from this year, including the ribociclib MONALEESA-2 trial and the ‘stunning’ results seen for palbociclib in the PALOMA-2 and PALOMA-3 trials. With regards to the toxicity profiles even though neutropenia was noted, it was suggested that these treatments remain a ‘paradigm shift’, as some patients remain on treatment for ‘10 months longer than endocrine therapy’. Another treatment looking at CDK 4/6 inhibition is abemaciclib, which has been shown to cause less neutropenia than the other treatments, but increased diarrhoea. The panel suggest this could be due to the increased activity against CDK4 and therefore gastrointestinal issues. The international panel confirmed that the optimism for the use of these treatments was seen in both US and Europe, due to the ‘magnitude of benefit’ seen. Some unresolved questions were posed, such as how the treatments are being sequenced and the use of them in the early breast cancer setting. Hoping to help answer this question is the PALLAS trial, which is evaluating the addition of 2 years of palbociclib to standard adjuvant endocrine therapy for patients with HR / HER2- early breast cancer (EBC). The panel then briefly touched on biomarkers, the use of CDK 4/6 inhibitors outside of ER BC, and the strength of PFS and time to chemotherapy as endpoints verses OS. It is clear that the significance of CDK 4/6 inhibition in breast cancer will continue to grow, with the importance of continuing medical education highlighted so that this breakthrough in the treatment of breast cancer can be appropriately managed.

Summing up data discussed at the ecancer CDK symposium at the St Gallen 2017 conference, Dr Giuseppe Curigliano (European Institute of Oncology, Milan, Italy), Dr Carmen Criscitiello (European Institute of Oncology, Milan, Italy), Dr Ghadeer Shubassi (Toronto, Canada) and Prof Pierfranco Conte - Istituto Oncologico Veneto, Padova, Italy) begin with a review of the MONALEESA trial program of ribociclib. In the PALOMA trials, Dr Criscitiello describes the successes of palbociclib of treating patients sensitive and resistant to endocrine therapy. Considering the therapeutic and financial value of establishing a prognostic biomarker, Dr Shubassi looks to substrates in the endocrine pathway that may prove useful, though none has yet been established. Prof Conte highlights that, for patients best suited to endocrine therapy, CDK therapy may be suitable in a second line setting, but that a number of long-term questions about CDK suitability remain unanswered. Discussion then turns to the significance of progression-free survival as a trial endpoint in comparison to overall survival, which requires data gathered over a time-scale not yet reached in any trial of CDK inhibition.

Elżbieta Senkus, Medical University of Gdansk, Department of Oncology and Radiotherapy, Gdańsk, Poland, (elsenkus@gumed.edu.pl) presents an overview of new therapies on the horizon for breast cancer in terms of data presented at the ESMO Congress, ASCO, and the San Antonio Breast Cancer Symposium. In the adjuvant setting, results from the MINDACT trial, which evaluated genomic versus clinical assessment for risk stratification, are described. Data on the role of anthracyclines in adjuvant chemotherapy is also discussed. In HER2-positive patients, dual HER2-targeted therapy was investigated in the KRISTINE study, and studies on the duration of adjuvant endocrine therapy in advanced breast cancer are also considered. Other ongoing studies in this population and the luminal population are also briefly mentioned. In the metastatic setting, the PALOMA-2 and MONALEESA-2 studies assessed the addition of CDK4/6 inhibitors to standard treatments. Results of the MONARCH 1 trial, evaluating a CDK4/6 inhibitor as a single agent, are also described, along with data on endocrine therapy in the luminal setting. Recent data on drugs interacting with the mTOR/PI3K/AKT pathway are considered. Studies in advanced HER-2 positive patients, considering HER-2 duel blockade plus either chemotherapy or endocrine therapy, are discussed. The situation in triple-negative breast cancer and advances and future directions in precision medicine and immunotherapy in breast cancer are briefly discussed. Read the abstract on the ESMO Open website: http://esmoopen.bmj.com/content/2/2/e000204.