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Guest host Dr. Nathan Pennell, of the Cleveland Clinic Taussig Cancer Institute, and Dr. Vamsi Velcheti, of the NYU Langone Perlmutter Cancer Center, discuss the ATLANTIS trial and other novel therapies in advanced SCLC, NSCLC, and malignant pleural mesothelioma featured at the 2022 ASCO Annual Meeting Poster Sessions.  Transcript   Dr. Nathan Pennell: Hello, I'm Dr. Nathan Pennell, your guest host for the ASCO Daily News Podcast, today. I'm the co-director of the Cleveland Clinic Lung Cancer Program and vice-chair of Clinical Research for the Taussig Cancer Institute.  My guest today is my friend Dr. Vamsidhar Velcheti, an associate professor and medical director of thoracic oncology at the Perlmutter Cancer Center at NYU Langone Health.  We'll be discussing key posters on lung cancer that will be featured at the 2022 ASCO Annual Meeting. Although the oral sessions tend to get the most press, we want to make sure you don't miss out on some high-impact abstracts that are presented in the poster session.  Our full disclosures are available in the show notes and disclosures of all guests on the podcast can be found on our transcripts at asco.orgpodcasts.  Vamsi, it's great to speak with you today.  Dr. Vamsidhar Velcheti: Thank you, Nate. It's a pleasure to discuss these 5 outstanding abstracts.  Dr. Nathan Pennell: Why don't we start with Abstract 9021, “Genomic correlates of acquired resistance to PD-(L)1 blockade in patients with advanced non—small cell lung cancer (NSCLC).” Vamsi, what were your key takeaways from this study?  Dr. Vamsidhar Velcheti: This is an important study in my opinion. This was a very large study of 1,700 patients from Dana Farber and the investigators looked at 45 specimens and matched pre- and post- immunotherapy treated patients. And they looked at the data mechanisms of resistance that were identified in 25 out of the 45 patients, that is 55% of the patients.  5 patients had acquired STK11 mutations. One patient had a KEAP1 alteration. There were several patients who had like KEAP1 SMARCA4 mutations. And interestingly, there were also some patients who developed KRAS-G12C mutation as well on the post-treatment specimens.  So, this is an interesting abstract. We typically don't do biopsies on patients progressing on immunotherapy. At this point, we don't have a standard clinical indication to do so. However, identifying these new novel mechanisms of genomic mechanisms of resistance is actually very important, because a lot of new therapy medications are being developed to target, for example, KEAP1, and could be approached to target microglobulin mutations. So, it's very important to kind of understand the mechanisms of resistance.  Dr. Nathan Pennell: Yeah, I completely agree. I mean, most of the benefits in second line in the refractory setting with targeted treatments came about through studies like this where there was broad sequencing of resistance and trying to understand and I think we're still kind of in the infancy of understanding resistance to immunotherapy, but it's a good start.  Abstract 9019 was another interesting study in non—small cell lung cancer. That was “A phase II study of AK112 (PD-1/VEGF bispecific) in combination with chemotherapy in patients with advanced non—small cell lung cancer.” Can you tell us a little bit about that study?  Dr. Vamsidhar Velcheti: Yeah, this is a multicenter phase-2 trial. This is an interesting agent. It's a PD-1/VEGF bispecific antibody developed by Akeso Bio. This is a single-arm study, and they did the study in 3 different cohorts.  One of the cohorts was patients with advanced non—small cell lung cancer who had wild-type EGFR/ALK, and they were treatment-naive. There was another cohort of patients where they enrolled patients with EGFR mutation who developed resistance to EGFR tyrosine kinase inhibitors (TKIs) and essentially progressed on osimertinib. And there was another cohort where patients were enrolled who were PD-1 refractory, they had prior PD-1or PD-1 chemo combination, and they had progressions. So, they enrolled a total of 133 patients, it was a decent-sized study, but a very early efficacy finding study.  In the cohort-1 which is the cohort that is enrolled with untreated patients with advanced non—small cell lung cancer. They had like 20 partial responses out of 26 patients that were evaluable and enrolled in the cohort, and there were 6 patients who had stable disease.  So, overall, the response rate was 76.9% and 100% disease control rate. So, this is a very small cohort and small data set. So, we have to interpret this with caution. But suddenly, a very interesting signal here for this VEGF/PD-1 bispecific antibody.  Dr. Nathan Pennell: The 40% response rate in the immunotherapy (IO) and chemo refractory patients, I thought was fairly interesting, although, as you said, very small numbers in these cohorts will have to be reproduced in larger trials.  Dr. Vamsidhar Velcheti: Right. I think there was a lot of excitement early on the IMpower150, right? With the combination of bevacizumab with chemo-theralizumab.  There seems to be some signal in terms of the addition of a VEGF inhibitor to immunotherapy. And we've seen that consistently in renal cells and other tumor types. So, I think this is a really intriguing signal. I think this definitely warrants further exploration.  So, the other interesting thing was cohort-2 where they enrolled patients who had progressed on EGFR TKIs. So, in that cohort, they had like 19 evaluable patients and 13 patients had a partial response and 5 had stable disease. So, a very respectable response rate of 68.4% and 94.7 disease control rate. So, again, very small numbers, but a nice signal here for the efficacy of the drug.  There was another cohort, which is the cohort-3 where they enrolled patients who progressed on PD-1 therapy, and they enrolled a total of 20 patients with 8 patients having a partial response, following progression on PD-1 therapy.  Dr. Nathan Pennell: Yeah, I look forward to seeing further follow-up on this. It definitely sounds interesting. Moving on to Abstract 8541. This was “Durvalumab (durva) after chemoradiotherapy (CRT) in unresectable, stage III, EGFR mutation-positive (EGFRm) NSCLC: A post hoc subgroup analysis from PACIFIC,' which of course was the study that led to the broad use of durvalumab, the anti-PD-L1 antibody after chemoradiotherapy for unresectable stage III non-small cell, but this was the post hoc subgroup analysis of the EGFR mutation-positive group. And this is a subgroup we've really been curious about whether there was a role for consolidation, immunotherapy, or not. And so, what are your thoughts on the study?  Dr. Vamsidhar Velcheti: I agree with you, Nate, that this is actually some data that I was really, really looking forward to. Before we actually talk about the abstract. What do you do for those patients? If you have an EGFR mutation patient who has stage IIIB, what do you do right now?  Dr. Nathan Pennell: It's a great question. I have a discussion with them about the potential pluses and minuses of doing consolidation durvalumab. But I actually don't always use durvalumab in this setting, because of concerns about if you're using durvalumab and they recur, perhaps there is a problem with toxicity with using osimertinib. Honestly, I go back and forth about what the right thing is to do in this subgroup.  Dr. Vamsidhar Velcheti: No, I think that's the right context. I think that's a good setup to kind of discuss the data from the trial. I'm really excited about this. And I'm glad that we have this data to look at.  So, as you pointed out, the Pacific trial, its U.S. Food and Drug Administration (FDA) approval for durvalumab in the consolidation setting for patients with stage III after chemoradiation. This has now been the standard of care for like a few years now. The problem with the study is that patients with EGFR/ALK were allowed to enroll in the study.  Typically, for most IO trials, we generally tend to see patients with EGFR/ALK being excluded. So, this trial was an exception. In this study, they actually presented a post-hoc exploratory analysis of efficacy and safety of patients who did consolidation with durvalumab, but there was a total of 35 patients of the 713 patients that were randomized in the trial. And out of the 35 patients with EGFR mutation, 24 received durvalumab and 11 received a placebo.  So, of course, you're going to interpret this data with a little bit of caution. This is a full stock analysis, not pre-planned in small numbers. In this dataset, essentially, the median progression-free survival (PFS) was not different among patients treated with durvalumab or placebo, and the median survival was also not statistically significant. Overall, there was not much benefit from adding durvalumab in this setting in patients who have EGFR mutation-positive stage III lung cancer.  Dr. Nathan Pennell: I think that tends to track along with what we who have been treating patients with EGFR mutations for years, and knowing the disappointing response rates, certainly in the advanced stage with immunotherapy, I think we were concerned that in this consolidation phase that it would also potentially be a relatively marginal benefit. I agree with you that 35 patients are too small to make any definitive conclusions, but it certainly isn't supportive of a large benefit.  Dr. Vamsidhar Velcheti: But I think I'm excited about the LAUREL study that's ongoing, hopefully, that'll give us a little bit more definitive answers as to what we should be doing for patients with EGFR mutation-positive disease. Suddenly this is a piece of information that's helpful for treating physicians to make some decisions on clinical management for these patients.  Dr. Nathan Pennell: I agree. Now moving beyond the non—small cell. Let's talk about “Final survival outcomes and immune biomarker analysis of a randomized, open-label, phase I/II study combining oncolytic adenovirus ONCOS-102 with pemetrexed/cisplatin (P/C) in patients with unresectable malignant pleural mesothelioma (MPM).” That's Abstract 8561. What were your takeaways here?  Dr. Vamsidhar Velcheti: Yeah, it's always good to see some new therapeutic options for patients with mesothelioma. This is somewhat of an orphan disease and we haven't seen a lot of advances. Granted, we have some new therapeutic options with immunotherapy now, like, there is now a standard of care in the frontline setting.  So, this particular approach with ONCOS-102 is an oncolytic adenovirus expressing GM-CSF. And this is intended to stimulate the local and systemic immune response and remodulate the tumor microenvironment.  This was a small phase 1 study where they had a CFT run-in of 6 patients and a total of 25 patients were randomly assigned to receive ONCOS-102 intratumorally with ultrasound guidance or CT guidance and they injected this oncolytic virus into the tumor directly.  They were also getting treatment with platinum pemetrexed which is the standard of care in the frontline setting. The control here was 6 cycles of platinum pemetrexed. So, they enrolled both the treatment-naive patients in the frontline setting and they also enrolled patients who will progress on a platinum doublet.  I should note that none of these patients were treated with immunotherapy. I think that's something that we'll kind of get back to and we'll discuss. Overall, from a safety standpoint, there were some expected toxicities like pyrexia and nausea which is seen in the experimental group. It's just kind of to be expected with an oncolytic virus. Overall, the 30-month survival rates were 34.3% and 18.2% in the control arm, and the median overall survival (OS) was 19.3 months and 18.3 in the controller.  So, for patients who were treated with the frontline chemotherapy, the survival rate was better with 30 months survival, it was 33.3 [months]. And in the experimental group, it was 0%.  So, overall, they also looked at tumor-infiltrating lymphocytes, they had CD4 around CD8 and granzyme B expressing CDA T-cells, and they had favorable PK from increased immune cell infiltration. So, this is very promising data but of course in a small study, and also in a population that hasn't had immunotherapy patients who are getting platinum doublet. In terms of safety, I think it looks promising. We need to see larger studies, especially with immunotherapy combinations.  Dr. Nathan Pennell: Yeah, I was impressed with the increased tumor infiltration of CD4 and CDA-positive T-cells, and the survival in the first line looked fairly impressive, although again, a very small subgroup of patients. But as you said, a standard of care these days is definitely going to involve immunotherapy. And so, I look forward to seeing combination trials in the future with this drug.  Shifting from mesothelioma over to small cell lung cancer, Abstract 8570 is “Stereotactic radiosurgery (SRS) versus whole brain radiation therapy (WBRT) in patients with small cell lung cancer (SCLC) and intracranial metastatic disease (IMD): A systematic review and meta-analysis.” Do you think that this would influence how we approach patients with brain metastases in the small cell?  Dr. Vamsidhar Velcheti: There are some in the community who kind of advocate for SRS in small cells if they have limited CNS disease. Certainly, I'm not one of them, but I think this is an interesting study in that light like we have never had any proper randomized trial. And we probably won't have randomized trials in that setting. So, at the end of the day, I think we all kind of customize our treatment approaches based on our patients and how much disease burden they have.  But having said that, the authors here have done a pretty large systemic analysis, and they looked at 3,700+ trials, they looked at random effects meta-analysis pooled hazard ratios for overall survival in patients who received SRS in the whole brain with or without SRS boost.  What they found was that overall survival following SRS was not inferior to whole brain RT. What do we really make out of this data? I think, given the heterogeneity, we have to see how the analysis was done and the kind of studies that went into the analysis. But however, I think the bigger question is, is there a population that we need to maybe—perhaps like, if somebody has an isolated brain met, you could potentially consider SRS with a whole brain RT for better local control.  So, the authors actually look at pooled data to look at local control versus intracranial distant control. So, this is a really interesting approach that asks the question, if patients had SRS and whole brain radiation, would it actually offer adequate intracranial distant control meaning like, do they develop new lesions?  So, it does look fairly decent. But again, it all depends on what kind of studies went into the analysis. And I don't think we should read too much into it. But at the same time, it kind of raises the question: is there a population of patients with small cell where it may be potentially appropriate to give SRS?  So, that's what I do in my day-to-day clinical practice. Sometimes there are situations where you kind of do the thing that we don't usually always do like in the small cell, we always think about whole brain radiation as something that we always have to offer, but I want to hear your perspectives too.  Dr. Nathan Pennell: No, I was always taught that you never did anything with whole brain radiation in the small cell even with a solitary metastasis. For a study like this, it's certainly interesting. You wonder how much selection bias there was towards people with fewer brain metastases and perhaps being in better health or better response to systemic disease that were referred for SRS, compared to whole brain radiation.  Part of the issue is the morbidity associated with whole brain radiation is significantly more than with SRS. And now that we are starting to, for the first time, see some patients with small cell [lung cancer] that are living substantially longer with immunotherapy, it might be worth exploring which patients might benefit from having that lower morbidity from whole brain radiation. But I agree with you that I'm not sure that we know who those patients are.  Dr. Vamsidhar Velcheti: Yeah, I think this is a difficult question to answer through a meta-analysis in my opinion. But having said that, your thought in terms of proving systemic therapies, then we kind of revisit the paradigm of offering SRS to some patients may be, especially with new BiTE T-cell engager studies that are ongoing, and hopefully, if you see some positive results, that might change what we do, but it's an important clinical question.  Dr. Nathan Pennell: And finally, in Abstract 8524, we have an interesting analysis of patients with relapsed small cell lung cancer, who received single-agent Lurbinectedin in the phase-3 Atlantis trial. What do you think about this poster, and why should this be on our radar?  Dr. Vamsidhar Velcheti: Yeah, I think this has been an interesting approval, of course, lurbinectedin FDA approved, as you know, like in June of 2020, based on data from a trial that uses 3.2 milligrams per meter square dosing every 21 days in second line setting post-chemotherapy.  What happened after that was there was a trial with the combination with doxorubicin in the second line setting comparative arm in that phase 3 trial topotecan or CAV.  In that trial, it was a negative trial, the primary endpoint was not met. The primary endpoint was overall survival, and it was a negative trial. And there were subgroup analyses done in the trial. The study that is presented now is actually a post-hoc analysis looking at patients who received treatment with this combination with doxorubicin that is like a lurbinectedin with doxorubicin, who had like a total of 10 cycles of the combination, and they switched to lurbinectedin monotherapy.  So, there were a total of 50 patients in that trial. They looked at the responses and the durability of responses in that population. It's a highly select population that made it to 10 cycles and they had stable disease or better and they switched to lurbinectedin monotherapy.  So, the highlight of the abstract is the median overall survival was 20.7 months. Of course, for small cell, that's really impressive. But I think we've got to be really careful in interpreting this data. This is like a small subgroup of highly selected patients who actually benefited from the trial. My question for you, Nate, is do you use lurbinectedin in the second line setting frequently or are you still treating them with topotecan?  Dr. Nathan Pannell: We still often use topotecan. I think lurbinectedin certainly seems to be an active drug, and it has some favorable schedule of administration pretty well tolerated from a tolerability standpoint, but from an efficacy standpoint, I still haven't really seen much that makes it stand out as significantly better than older options like topotecan or irinotecan.  That being said, it is intriguing that there is a subgroup of people who seem to have prolonged disease control with this. The problem, of course, is if you already select the people who make it 10 cycles without progression, then you're already picking the group of people who are doing extremely well. So, it's not surprising that they would continue to do extremely well.  Nonetheless, it's a sizable subgroup of people that seem to benefit and it would really be nice if there was, for example, a biomarker that might tell us which patients would truly benefit from this drug compared to our other options.  Dr. Vamsidhar Velcheti: Yeah, exactly. True. Right, I mean, like all of us have patients who have done exceedingly well on topotecan and I had a patient on paclitaxel for years. So, it's really important to kind of keep that in mind when we look at these sub-proof post hoc analyses.  Dr. Nathan Pennell: Well, thanks Vamsi for sharing these important advances in lung cancer that will be featured at the 2022 ASCO Annual Meeting.  Dr. Vamsidhar Velcheti: Thank you, Nate.  Dr. Nathan Pennell: 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. Nathan Pennell:   Consulting or Advisory Role: AstraZeneca, Lilly, Cota Healthcare, Merck, Bristol-Myers Squibb, Genentech, Amgen, G1 Therapeutics, Pfizer, Boehringer Ingelheim, Viosera, Xencor, Mirati Therapeutics, Janssen Oncology, Sanofi/Regeneron  Research Funding (Inst): Genentech, AstraZeneca, Merck, Loxo, Altor BioScience, Spectrum Pharmaceuticals, Bristol-Myers Squibb, Jounce Therapeutics, Mirati Therapeutics, Heat Biologics, WindMIL, Sanofi  Dr. Vamsidhar Velcheti:  Honoraria: ITeos Therapeutics  Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine , AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen  Research Funding (Institution): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline  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.   

An interview with Dr. David Schiff from the University of Virginia Medical Center in Charlottesville, VA, and Dr. Michael Vogelbaum from Moffitt Cancer Center in Tampa, FL, co-chairs on “Treatment for Brain Metastases: ASCO-SNO-ASTRO Guideline.” This guideline comprehensively addresses the treatment of brain metastases from non-hematologic solid tumors, including surgery, systemic therapy, radiation therapy, and timing of therapy. Read the full guideline at www.asco.org/neurooncology-guidelines.   TRANSCRIPT [MUSIC PLAYING] SPEAKER 1: 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. BRITTANY HARVEY: Hello, and welcome to the ASCO Guidelines podcast series brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at asco.org/podcasts. My name is Brittany Harvey, and today I am interviewing Dr. Michael Vogelbaum from Moffitt Cancer Center in Tampa, Florida, and Dr. David Schiff from the University of Virginia Medical Center in Charlottesville, Virginia, Co-chairs on Treatment for Brain Metastases, American Society of Clinical Oncology, Society for Neuro-Oncology, and American Society for Radiation Oncology Guideline. Thank you for being here, Dr. Vogelbaum and Dr. Schiff. MICHAEL VOGELBAUM: My pleasure. BRITTANY HARVEY: Before we begin, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online with the publication of the guideline in The Journal of Clinical Oncology Dr. Vogelbaum, do you have any relevant disclosures that are directly related to this guideline topic? MICHAEL VOGELBAUM: I have no disclosures relevant to this guideline. BRITTANY HARVEY: Thank you. Then, Dr. Schiff, do you have any relevant disclosures that are directly related to this guideline topic. DAVID SCHIFF: Hi, Brittany. No, I do not. BRITTANY HARVEY: Great. Then first, Dr. Schiff, can you give us an overview of the scope and the purpose of this guideline? DAVID SCHIFF: Sure. Our overall purpose was to provide guidance on the appropriate treatment of adult patients with parenchymal brain metastases from solid tumors, encompassing surgery, radiation, and systemic therapy, as well. Previous guidelines in this area were for the most part produced by neurosurgeons and radiation oncologists for their respective professional organizations, although they did incorporate multidisciplinary input. But over the last decade, treatment options for certain types of brain metastases have undergone a substantial change. The expanding armamentarium for medical oncologists in treating both extra-CNS disease as well as brain metastases highlighted the need for a new set of guidelines to evaluate the role of systemic approaches, such as targeted agents and immunotherapy, for the primary treatment of brain metastases in the context of more established treatments like surgical resection, radiosurgery, and fractionated radiotherapy. Additionally, recent studies have clarified the role of radiation techniques like whole brain radiation with hippocampal avoidance and radiosurgery to surgical resection cavities. By assembling a multidisciplinary group of experts from surgical neuro-oncologists, medical oncologists, neuro-oncologists, and radiation oncologists, we sought to provide as comprehensive and up to date a set of therapeutic guidelines as possible. In order to accomplish this, the panel performed a systematic review of randomized as well as nonrandomized evidence from 2008 through April, 2020. We focused on the roles of surgery, systemic therapy, and radiation therapy, as well as the timing and interactions among these modalities. And we included all randomized clinical trials, as well as large single arm phase II studies and institutional case series, and we also reviewed case control and cohort studies. BRITTANY HARVEY: OK, great. That's helpful background. And then you mentioned a couple focus areas, as well, of the systematic review. And so I'd like to review the key recommendations that were based off that evidence. So, starting with surgery, Dr. Vogelbaum, what are the key recommendations for surgery in adult patients with brain metastases? MICHAEL VOGELBAUM: So, the role of surgery, I think, was well established via randomized trials to some degree, and then via some of the larger single arm studies. Patients with suspected brain metastases without a primary cancer diagnosis were felt to benefit from surgery to obtain a diagnosis and undergo removal of the tumor. But more to the point, patients with larger tumors with mass effect-related symptoms are the ones most likely to benefit from surgery. What we also noted was that patients who have multiple brain metastases with extensive and uncontrolled systemic disease are unlikely to benefit from surgery unless the remaining disease is controlled via other measures, typically medical measures. We also contemplated the type of resection performed, the technique being used. There was some developing literature looking at the techniques of either an en bloc resection or a piecemeal resection. And when we critically evaluated the literature, we felt that no recommendation could be made regarding the method of resection, as there was not sufficient evidence to support one approach over another. Another technique that is being used more recently is the use of laser interstitial thermal therapy, which is a minimally invasive technique to treat tumors in general. But again, there was insufficient evidence to really be able to make a recommendation for or against the use of LITT, as it's called. BRITTANY HARVEY: OK, thank you for reviewing both those techniques and those recommendations and highlighting where there wasn't enough evidence to actually make a recommendation. So, then, following that, Dr. Schiff, what does the guideline recommend for patients with brain metastases regarding systemic therapy, including chemotherapy, immunotherapy, and targeted agents? DAVID SCHIFF: Brittany, there is a role for systemic therapy as the initial or primary modality in some cases, but I think it's really important to emphasize this only pertains to patients whose brain metastases are asymptomatic and those with particular histologies or molecular profiles. So, there are really-- there are three primary sites for which targeted or immunotherapy can be considered. The first is non-small cell lung cancer, for which osimertinib, or if you're in China, where there's access to another drug called icotinib, specifically for EGFR-mutated disease, alectinib, brigatinib, and ceritinib are appropriate approaches in ALK-rearranged asymptomatic brain metastases. And finally, pembrolizumab in combination with pemetrexed and a platinum agent in immunotherapy naive patients whose tumors express PD-L1. The second primary tumor is melanoma. And for melanoma patients who have asymptomatic BRAF V600E mutant brain metastases, dabrafenib with trametinib is an appropriate option to consider. For all melanoma patients with asymptomatic brain metastases, ipilimumab with nivolumab is also an option. And finally, for breast cancer, the combination of tucatinib, trastuzumab, and capecitabine for HER2 positive asymptomatic brain metastases in patients who have progressed on previous anti-HER2 antibody therapy. When patients treated with systemic therapy progress intracranially, local therapies such as surgery, radiation, and radiosurgery should not be deferred. BRITTANY HARVEY: OK, those are helpful notes for clinicians, and particularly around the primary tumor sites. So, then, Dr. Vogelbaum, what are the key recommendations for radiation therapy in patients with brain metastases? MICHAEL VOGELBAUM: So, Brittany, the panel started by noting which patients would not benefit from radiation therapy, in particular, those with asymptomatic brain metastases and a poor performance status, with a Karnofsky Performance Score, or KPS, of less than or equal to 50, or performance status of less than 70 and no systemic therapy options. In those cases, radiation therapy is unlikely to be of real benefit. But then when speaking to the different modalities of radiation to be used, a lot of the review focused on the two most commonly used modalities, which is Stereotactic Radiosurgery, or SRS, versus Whole Brain Radiotherapy, or WBRT. And the first recommendation was that SRS alone as opposed to either whole brain radiotherapy alone or a combination of the two should be offered to patients with one to four unresected brain metastases, except for the situation of small cell carcinoma, which has a different approach that's used often with prophylactic cranial irradiation. So, that's a separate group. But for others, SRS is the modality that should be offered. And then for patients who underwent surgical resection of their brain metastases, we know that there needs to be some form of radiation treatment to the surgical cavity. And the recommendation was that SRS alone should be offered to those patients if the surgical cavity can be safely treated, and considering the extent of remaining intracranial disease. Obviously, for patients who have a lot of disease but otherwise have a treatable systemic disease, then whole brain radiotherapy may make more sense. But for the ones that are more limited after surgery, it should be SRS. And then when the panel considered a situation where you have patients with more than four unresected metastases and the options included radiosurgery, whole brain radiotherapy, or radiosurgery plus whole brain radiotherapy-- and in general, these are reasonable options. But it was felt that SRS may be preferred for patients with better prognosis or where systemic therapy that is known to be active in the central nervous system is available. Additional recommendations revolved around both protective, radioprotective, and radiosensitizing agents. So, in terms of trying to protect memory, there are two approaches that are used. One is to give memantine during whole brain radiotherapy, or to do whole brain radiotherapy using a hippocampal avoidance technique. And it was felt that either one of those or both should be offered to patients who will receive whole brain radiotherapy and have no tumors in the hippocampus, and they're expected to live more than four months. And then finally, that radiation sensitizing agents should not be offered to patients, because they've not been shown to be effective. BRITTANY HARVEY: Understood. And it's helpful to know both what those recommendations are for specific approaches, and as you said, critical to know who will and who will not benefit from radiation therapy. So, then we've just reviewed the key surgery, systemic therapy, and radiation therapy recommendations. Dr. Schiff, did the panel recommend anything regarding the timing of surgery, radiation therapy, and systemic therapy? MICHAEL VOGELBAUM: The panel had just a couple of points in this regard. Although there are some recent data suggesting a decreased incidence of leptomeningeal metastases in patients who undergo radiosurgery before craniotomy, as compared to the reverse sequence, the panel concluded no recommendation on this point regarding the specific sequence of therapy could be made. And to reiterate, for those circumstances in which systemic therapy may be of use for brain metastases, that therapy should proceed, local therapy like surgery or radiation, only if the brain metastases are asymptomatic. BRITTANY HARVEY: Great. Thank you both for reviewing these recommendations. In your view, Dr. Vogelbaum, what is the importance of this guideline, and how will it impact clinicians? MICHAEL VOGELBAUM: I think one of the important points that David raised that at the beginning was that this really is the most comprehensive look at the evidence revolving around the treatment of patients with brain metastases and leptomeningeal disease. And in particular, this may be new information for an audience that has not been involved in that treatment for many decades, the medical oncology community. So, I think some of the impact on clinicians may be that the guidelines will help them understand the durability of surgery and radiosurgery, and those had been the only treatments available for a long time. And so now we have these new medical therapies that are showing activity in the brain, but one needs to balance that against what is known about the effective treatments in the past. Some of the new targeted immunotherapies may not provide as consistent or durable of a benefit as has been shown previously with surgery and radiotherapy. Hopefully, understanding this challenge with respect to consistency and durability will serve to support the development of phase 0 or window of opportunity clinical trials to better understand the determinants the biological determinants of response or resistance to systemic therapies we want to improve on that, for sure, and those clinical trials are going to be essential for us to be able to do that. And then ultimately, also, identify opportunities to synergistically combine radiation and medical therapies and better understand the timing of these combinations. This is a great area for clinical trial development in the future. BRITTANY HARVEY: Definitely. We'll look forward to future research in those areas. So then, finally, Dr. Schiff, to wrap us up, how will these guideline recommendations affect patients? DAVID SCHIFF: Yeah. Over the last 30 years, the management of brain metastases have involved hugely, from an area where almost everyone got whole brain radiation therapy and many patients died from their brain disease. The use of local therapies like surgical resection and radiosurgery has greatly improved local control of brain metastases. And with options like radiosurgery alone for a limited number of brain metastases, systemic therapies as the initial approach, and hippocampal avoidant whole brain radiation therapy with memantine, patients are experiencing improved long term cognitive function and quality of life, as well. So, I think the careful delineation of the role of each of these modalities that these guidelines provide will really help maximize benefit and minimize the risk for this very large number of cancer patients. BRITTANY HARVEY: Definitely, improve quality of life is always a goal. So, I want to thank you both for your work on these guidelines and thank you for taking the time to speak with me today, Dr. Vogelbaum and Dr. Schiff. DAVID SCHIFF: My pleasure. MICHAEL VOGELBAUM: Thank you, Brittany. BRITTANY HARVEY: And thank you to all of our listeners for tuning in to the ASCO Guidelines podcast series. To read the full guideline, go to www.asco.org/neurooncology guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in iTunes or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe, so you never miss an episode. [MUSIC PLAYING]

In this podcast episode, listen to breast cancer experts Thomas Bachelot, MD, PhD; Adam M. Brufsky, MD, PhD; and Cristina Saura, MD, PhD, discuss clinical considerations for patients with HER2-positive MBC, with topics including:Local therapy in the context of MBCChoice of therapy after progression on available standards of careChoice of trastuzumab deruxtecan and tucatinib based on patient presentationManaging patients with CNS metastasesManaging interstitial lung diseasePresenters:Thomas Bachelot, MD, PhDChair, Unicancer Breast Group - UCBGBreast Cancer UnitMedical Oncology Centre Léon BérardLyon, FranceAdam M. Brufsky, MD, PhDProfessor of Medicine Hematology/Oncology University of Pittsburgh School of MedicineAssociate Chief, Hematology-OncologyUniversity of Pittsburgh Cancer InstitutePittsburgh, PennsylvaniaCristina Saura, MD, PhDMedicine and Surgery/Medical OncologyUniversidad Universitat Autònoma Barcelona and Vall d’Hebron Institute of Oncology (VHIO)Head, Breast Cancer ProgramMedical OncologyVall d’Hebron University HospitalBarcelona, SpainContent based on an online CME program supported by an educational grant from Daiichi Sankyo, Inc. Link to full program, including associated downloadable slidesets:https://bit.ly/32A1HMb

Talcum powder, FLAURA, Oncotype and LRR, Vegetables & Prostate Cancer, "Flu Shot", WBRT for Alzheimer's, FLASH quadshotnews@gmail.com @QuadShotNews

Dr Buckner talks to ecancertv at ASCO 2015 about a federally funded phase III trial that is providing additional information regarding a long-standing discussion about the impact of adjuvant whole brain radiation therapy (WBRT) on cognitive function.

Dr Buckner presents, at a press conference at ASCO 2015, a federally funded phase III trial that is providing additional information regarding a long-standing discussion about the impact of adjuvant whole brain radiation therapy (WBRT) on cognitive function.

Drs. Ben Solomon, Leora Horn, & Jack West discuss whether the data highlighting cognitive deficits from whole brain radiation therapy (WBRT) for patients with brain metastases should change our recommendations for prophylactic cranial irradiation (PCI).

Drs. Ben Solomon, Leora Horn, & Jack West discuss whether the data highlighting cognitive deficits from whole brain radiation therapy (WBRT) for patients with brain metastases should change our recommendations for prophylactic cranial irradiation (PCI).

Drs. Ben Solomon, Leora Horn, & Jack West discuss whether the data highlighting cognitive deficits from whole brain radiation therapy (WBRT) for patients with brain metastases should change our recommendations for prophylactic cranial irradiation (PCI).

Managing brain metastases is a big concern for lung cancer patients. The doctors discuss the drawbacks of whole brain radiotherapy and the fact that there are still unknowns regarding more targeted stereotactic radiosurgery.

Managing brain metastases is a big concern for lung cancer patients. The doctors discuss the drawbacks of whole brain radiotherapy and the fact that there are still unknowns regarding more targeted stereotactic radiosurgery.

Managing brain metastases is a big concern for lung cancer patients. The doctors discuss the drawbacks of whole brain radiotherapy and the fact that there are still unknowns regarding more targeted stereotactic radiosurgery.

Radiation Oncologist Dr. Vivek Mehta reviews the concept of using whole brain radiation for multiple brain metastases, including how it is delivered and risks and benefits of this strategy.

Radiation Oncologist Dr. Vivek Mehta reviews the concept of using whole brain radiation for multiple brain metastases, including how it is delivered and risks and benefits of this strategy.

Radiation Oncologist Dr. Vivek Mehta reviews the concept of using whole brain radiation for multiple brain metastases, including how it is delivered and risks and benefits of this strategy.

A phase three clinical trial studying whole brain radiation treatment (WBRT) has found that in patients with brain metastases, WBRT has a negative impact on memory recall and verbal fluency. Study leader and MD Anderson radiation oncologist Paul Brown, M.D., presented his findings at the 2015 meeting of the American Society of Clinical Oncologists. Brown says the impact of whole brain radiation on patients' quality of life far outweigh its effectiveness as a treatment.

Background: In the present study factors affecting survival and toxicity in cerebral metastasized patients treated with stereotactic radiosurgery (SRS) were analyzed with special focus on radiation necrosis. Patients and methods: 340 patients with 1-3 cerebral metastases having been treated with SRS were retrospectively analyzed. Radiation necrosis was diagnosed by MRI und PET imaging. Univariate and multivariate analysis using a Cox proportional hazards regression model and log-rank test were performed to determine the prognostic value of treatment-related and individual factors for outcome and SRS-related complications. Results: Median overall survival was 282 days and median follow-up 721 days. 44% of patients received WBRT during the course of disease. Concerning univariate analysis a significant difference in overall survival was found for Karnofsky Performance Status (KPS

Anthony Zietman talks with author Nadia Laack about this game-changing research

Question and answer session with Dr. Minesh Mehta, Professor of Radiation Oncology at Northwestern University, on topics related to treatments for brain metastases and related complications, especially in the setting of lung cancer.

Question and answer session with Dr. Minesh Mehta, Professor of Radiation Oncology at Northwestern University, on topics related to treatments for brain metastases and related complications, especially in the setting of lung cancer.

Dr. Minesh Mehta, Professor of Radiation Oncology at Northwestern University, describes benefits and risks of multiple interventions that are currently used or being studied to reduce risk of developing brain metastases or treat established metastases.

Dr. Minesh Mehta, Professor of Radiation Oncology at Northwestern University, describes benefits and risks of multiple interventions that are currently used or being studied to reduce risk of developing brain metastases or treat established metastases.