Podcasts about impower

Eskom says no load shedding this winter—but unplanned outages are already above safe levels. Zain Johnson speaks to energy expert Matthew Cruise on whether SA can really keep the lights on this winter.See omnystudio.com/listener for privacy information.

Stage 2 load shedding is back — Africa Melane speaks to IMPOWER energy expert Matthew Cruise about Eskom’s latest challenges. With over 13,000MW in losses, delayed maintenance, and rising winter demand, is the grid more fragile than Eskom admits?See omnystudio.com/listener for privacy information.

Africa Melane talks to energy analyst Matthew Cruise about Eskom’s big next move — getting ready to borrow again. After years under a strict debt relief plan, South Africa’s power giant says it will soon return to the markets. They unpack Eskom’s new borrowing limits, where the billions will go, why municipal debt remains a crisis, and whether this signals a genuine financial turnaround or just a new cycle of risk. Follow us on:CapeTalk on Facebook: www.facebook.com/CapeTalkCapeTalk on TikTok: www.tiktok.com/@capetalkCapeTalk on Instagram: www.instagram.com/capetalkzaCapeTalk on YouTube: www.youtube.com/@CapeTalk567CapeTalk on X: www.x.com/CapeTalkSee omnystudio.com/listener for privacy information.

South Africa’s power giant is losing ground as demand drops, industries move away, alternative energy rises and announcements of a possible loadshedding. Africa Melane speaks to Energy expert at Impower, Matthew Cruise.See omnystudio.com/listener for privacy information.

Guest: Matthew Cruise | Energy Expert at Impower The US exits South Africa’s R168.7 billion energy transition deal, but the plan moves forward. Africa Melane speaks to energy expert at Impower, Matthew Cruise to discuss the way forward.See omnystudio.com/listener for privacy information.

Stage 6 load shedding returns! Eskom blames breakdowns and maintenance, but is there more to the story? Africa Melane speaks to energy expert Matthew Cruise from Impower to unpack South Africa’s latest power crisis with Africa Melane.See omnystudio.com/listener for privacy information.

John Maytham is joined by Matthew Cruz, energy expert at IMPOWER. He’ll break down the details of NERSA’s net-billing framework, how compensation rates will be determined, and what challenges remain in implementing this system effectively. See omnystudio.com/listener for privacy information.

This week on the KORE Women podcast, Dr. Summer Watson welcomes Kandice Garcia Tomkins, RN, MS, a leader in Quality Improvement (QI) education and healthcare transformation. Kandice has been developing QI programs since 2014, partnering with Dr. David Larson, and currently serves as the QI Director for the ACR Learning Network, where her program ImPower helps healthcare professionals drive impactful projects. She's also a performance improvement specialist at Stanford University and the founder of Tungsten QI Partners, where she leads a team of consultants shaping the future of healthcare quality improvement across the nation. You can follow Kandice Garcia Tomkins on LinkedIn and at: kandice.garcia@gmail.com Thank you for taking the time to listen to the KORE Women podcast and being a part of the KORE Women experience. You can listen to The KORE Women podcast on your favorite podcast directory - Pandora, iHeartRadio, Apple Podcast, Google Podcast, YouTube, Spotify, Stitcher, Podbean, JioSaavn, Amazon and at: https://m.youtube.com/@korewomen7481.  Please leave your comments and reviews about the podcast and check out KORE Women on Instagram, Twitter, and Facebook. You can also learn more about the host, Dr. Summer Watson and KORE Women at: www.korewomen.com You can also learn more about Dr. Summer Watson, MHS, PhD, KORE Women, LLC, the KORE Women podcast, and her Community Empowerment and Cross-Generational Consultation Services by going to: www.korewomen.com. Thank you for listening! Please share this podcast with your family and friends.

Mathew cruise Energy Expert at Impower. See omnystudio.com/listener for privacy information.

In der aktuellen Folge des Verwaltung4U-Podcasts begrüßt Massimo Füllbeck einen Herrn Jürgen Forscht, Geschäftsführer von Impower und erfahrener Verwalter. Gemeinsam sprechen sie über die Herausforderungen und Chancen der Digitalisierung in der Immobilienverwaltung. Impower, ein ERP-System speziell für Haus- und WEG-Verwalter, setzt den Fokus auf automatisierte Buchhaltung und moderne IT-Lösungen. Forscht teilt Einblicke in die Entwicklung von Impower und wie das System Verwaltern hilft, effizienter und transparenter zu arbeiten. Dabei werden auch größere Trends wie das Bürokratieentlastungsgesetz und die Einführung von eRechnungen thematisiert. Kernpunkte der Folge: Warum viele Softwarelösungen den Anforderungen moderner Verwalter nicht mehr gerecht werden. Wie Impower durch Automatisierung Fehlerquellen reduziert und Zeit spart. Die Bedeutung der Digitalisierung für Transparenz in der Verwaltung – vom Dokumentenmanagement bis zur eRechnung. Einblick in gesetzliche Änderungen, wie das Bürokratieentlastungsgesetz und das Wachstumschancengesetz, die die Immobilienverwaltung verändern. Erfahrungen aus der Praxis: Wie kleinere Verwaltungen mit begrenzten Ressourcen von modernen IT-Lösungen profitieren können. Diese Folge liefert wertvolle Erkenntnisse für alle, die an einer zukunftsorientierten Immobilienverwaltung interessiert sind. Egal, ob Sie Quereinsteiger oder erfahrener Verwalter sind – die Einblicke und Tipps aus diesem Gespräch sind inspirierend und praxisnah. Ihre EBZ Akademie  Für Anmerkungen, Fragen, Lob und Kritik schreiben Sie gerne an die Redaktion: verwaltung4u@e-b-z.de  Weiterbildungsangebote der EBZ-Akademie finden Sie online in unserem Bildungsfinder: ⁠⁠⁠⁠⁠⁠⁠https://www.ebz-training.de/⁠⁠⁠⁠⁠⁠⁠ oder auf unserer Homepage: ⁠⁠⁠⁠https://ebz-akademie.de/⁠⁠⁠⁠⁠⁠  LEARNING | Fachwissen für die Immobilienwirtschaft  CONSULTING | Partner in der Transformation  NETWORKING | Gemeinsam stark 

In a world of squeezed budgets and increasing demand, improving outcomes while saving money has become the holy grail for local government. In this special episode LGC, in association with IMPOWER, is delving deep into one place's quest to transform health and social care services to do just that. Manchester's Better Outcomes, Better Lives programme brought health and social care services together at neighbourhood level to improve support for residents in need of social care and avoid more than £39m in costs. LGC editor Sarah Calkin is joined by Bernie Enright, Manchester City Council's executive director for adult social services, Katy Calvin-Thomas, chief executive of the Manchester and Trafford local care organisations and Oliver Barnes, delivery director at IMPOWER to discuss how they did it. Read more: Bernadette Enright: Delivering ‘good savings' in adult social care

In this rapid webinar, Meredith E. Clement, MD, and Linda-Gail Bekker, MBChB, DTMH, DCH, FCP(SA), PhD, provide an overview of important topics and studies presented at HIVR4P 2024, including:Expanding PrEP options based on results from PURPOSE 2, IMPOWER-22, IMPOWER-24, IPM 054, MTN-025/HOPE OLE, CATALYST, and the HPTN 084 substudyImplementing injectable PrEP based on results from PEPFAR, the USAID DISCOVER-Health LA CAB Demonstration Project in Zambia, and the LA CAB PrEP Rapid Start Model in Public Health ClinicsImproving PrEP uptake based on results from SPrEP and HPTN 091  Presenters:Meredith E. Clement, MDAssociate ProfessorInfectious DiseasesLouisiana State University Health Sciences CenterNew Orleans, LouisianaLinda-Gail Bekker, MBChB, DTMH, DCH, FCP(SA), PhDDirector and Professor, The Desmond Tutu HIV Centre, UCTCEO, The Desmond Tutu Health FoundationCape Town, South AfricaTo access all of our new podcast episodes, subscribe to the CCO Infectious Disease Podcast on Apple Podcasts, Google Podcasts, or Spotify. Link to full program: https://bit.ly/3NJIDSA

In this rapid webinar, Meredith E. Clement, MD, and Linda-Gail Bekker, MBChB, DTMH, DCH, FCP(SA), PhD, provide an overview of important topics and studies presented at HIVR4P 2024, including:Expanding PrEP options based on results from PURPOSE 2, IMPOWER-22, IMPOWER-24, IPM 054, MTN-025/HOPE OLE, CATALYST, and the HPTN 084 substudyImplementing injectable PrEP based on results from PEPFAR, the USAID DISCOVER-Health LA CAB Demonstration Project in Zambia, and the LA CAB PrEP Rapid Start Model in Public Health ClinicsImproving PrEP uptake based on results from SPrEP and HPTN 091 Presenters:Meredith E. Clement, MDAssociate ProfessorInfectious DiseasesLouisiana State University Health Sciences CenterNew Orleans, LouisianaLinda-Gail Bekker, MBChB, DTMH, DCH, FCP(SA), PhDDirector and Professor, The Desmond Tutu HIV Centre, UCTCEO, The Desmond Tutu Health FoundationCape Town, South AfricaTo access all of our new podcast episodes, subscribe to the CCO Infectious Disease Podcast on Apple Podcasts, Google Podcasts, or Spotify. Link to full program: https://bit.ly/3NJIDSA

Continually looking for savings and efficiencies in the quest to balance the books has become a way of life for local authorities. But striking the balance between achieving savings in the short term without storing up more problems for the future is challenging and can require political and managerial bravery. In this episode of The Local Authority LGC, in association with Impower, explores what good savings look like and how councils can deliver more of them. LGC editor Sarah Calkin is joined by: Martin Reeves, chief executive, Oxfordshire CC Mark Smith, director of public service reform, Gateshead MBC Ebony Hughes, chief operating officer, Impower

Drs. Vamsi Velcheti and Nathan Pennell discuss novel approaches and key studies in lung cancer that were showcased at the 2024 ASCO Annual Meeting, including the Plenary abstracts LAURA and ADRIATIC.   TRANSCRIPT Dr. Vamsi Velcheti: Hello, I am Dr. Vamsi Velcheti, your guest host for the ASCO Daily News Podcast today. I'm a professor of medicine and director of thoracic medical oncology at the Perlmutter Cancer Center at NYU Langone Health. Today, I'm joined by Dr. Nate Pennell, the co-director of the Cleveland Clinic Lung Cancer Program and the vice chair of clinical research at the Taussig Cancer Center in Cleveland Clinic. Dr. Pennell is also the editor-in-chief of the ASCO Educational Book. Today, we will be discussing practice-changing abstracts and the exciting advances in lung cancer that were featured at the ASCO 2024 Annual Meeting. You'll find our full disclosures in the transcript of the episode. Nate, we're delighted to have you back on the podcast today. Thanks for being here. It was an exciting Annual Meeting with a lot of important updates in lung cancer. Dr. Nate Pennell: Thanks, Vamsi. I'm glad to be back. And yes, it was a huge year for lung. So I'm glad that we got a chance to discuss all of these late-breaking abstracts that we didn't get to talk about during the prelim podcast. Dr. Vamsi Velcheti: Let's dive in. Nate, it was wonderful to see all the exciting data, and one of the abstracts in the Plenary Session caught my attention, LBA3. In this study, the investigators did a comparative large-scale effectiveness trial of early palliative care delivered via telehealth versus in-person among patients with advanced non-small cell lung cancer. And the study is very promising. Could you tell us a little bit more about the study and your take-home messages? Dr. Nate Pennell: Yes, I think this was a very important study. So just to put things in perspective, it's now been more than a decade since Dr. Jennifer Temel and her group at Massachusetts General Hospital did a randomized study that showed that early interventions with palliative medicine consultation in patients with advanced non-small cell lung cancer significantly improves quality of life and in her initial study, perhaps even overall survival. And since then, there have been numerous studies that have basically reproduced this effect, showing that getting palliative medicine involved in people with advanced cancer, multiple different cancer types, really, has benefits.  The difficulty in applying this has been that palliative care-trained specialists are few and far between, and many people simply don't have easy access to palliative medicine-trained physicians and providers. So with that in mind, Dr. Temel and her group designed a randomized study called the REACH PC trial, where 1,250 patients were randomized with advanced non-small cell lung cancer to either in-person palliative medicine visits which is sort of the standard, or one in-person assessment followed by monthly telemedicine video visits with palliative medicine. Primary endpoint was essentially to show that it was equivalent in terms of quality of life and patient satisfaction. And what was exciting about this was that it absolutely was. I mean, pretty much across the board in all the metrics that were measured, the quality-of-life, the patient satisfaction, the anxiety and depression scores, all were equivalent between doing telemedicine visits and in-person visits. And this hopefully will now extend the ability to get this kind of benefit to a much larger group of people who don't have to geographically be located near a palliative medicine program. Dr. Vamsi Velcheti: Yeah, I think it's a great abstract, Nate and I actually was very impressed by the ASCO committee for selecting this for the Plenary. We typically don't see supportive care studies highlighted in such a way at ASCO. This really highlights the need for true interdisciplinary care for our patients. And as you said, this study will clearly address that unmet need in terms of providing access to palliative care for a lot of patients who otherwise wouldn't have access. I'm really glad to see those results. Dr. Nate Pennell: It was. And that really went along with Dr. Schuchter's theme this year of bringing care to patients incorporating supportive care. So I agree with you.  Now, moving to some of the other exciting abstracts in the Plenary Session. So we were talking about how this was a big year for lung cancer. There were actually 3 lung cancer studies in the Plenary Session at the Annual Meeting. And let's move on to the second one, LBA4, the LAURA study. This was the first phase 3 study to assess osimertinib, an EGFR tyrosine kinase inhibitor, in patients with EGFR mutant, unresectable stage III non-small cell lung cancer. What are your takeaways from this study?  Dr. Vamsi Velcheti: This is certainly an exciting study, and all of us in the lung community have been kind of eagerly awaiting the results of the study. As you know, for stage III non-small cell lung cancer patients who are unresectable, the standard of care has been really established by the PACIFIC study with the consolidation durvalumab after definitive concurrent chemoradiation. The problem with that study is it doesn't really answer the question of the role of immunotherapy in patients who are never-smokers, and especially in patients who are EGFR positive tumors, where the role of immunotherapy in a metastatic setting has always been questioned. And in fact, there have been several studies as you know, in patients with EGFR mutation positive metastatic lung cancer where immunotherapy has not been that effective. In fact, in the subgroup analysis in the PACIFIC study, patients with EGFR mutation did not really benefit from adding immunotherapy.  So this is an interesting study where they looked at patients with locally advanced, unresectable stage III patients and they randomized the patients 2:1 to osimertinib versus placebo following concurrent or sequential tumor radiation. The primary endpoint for the study was progression free survival, and a total of 216 patients were enrolled and 143 patients received a study treatment, which is osimertinib, and 73 received placebo. And 80% of the patients on the placebo arm crossed over to getting treatment at the time of progression.  So most of us in the lung cancer community were kind of suspecting this would be a positive trial for PFS. But however, I think the magnitude of the difference was truly remarkable. The median PFS in the osimertinib arm was 39.1 months and placebo was 5.6 months and the hazard ratio of 0.16. So it was a pretty striking difference in terms of DFS benefit with the osimertinib consolidation following chemoradiation. So it was truly a positive study for the primary endpoint and the benefit was seen across all the subgroups and the safety was no unexpected safety signals other than a slight increase in the radiation pneumonitis rates in patients receiving osimertinib and other GI and skin tox were kind of as expected. In my opinion, it's truly practice changing and I think patients with EGFR mutation should not be getting immunotherapy consolidation post chemoradiation. Dr. Nate Pennell: I completely agree with you. I think that this really just continues the understanding of the use of osimertinib in EGFR-mutant lung cancer in earlier stages of disease. We know from the ADAURA trial, presented twice in the Plenary at the ASCO Annual Meeting, that for IB, stage II and resectable IIIA, that you prolong progression free or disease free survival. So this is a very similar, comparable situation, but at an even higher risk population or the unresectable stage III patients. I think that the most discussion about this was the fact that the osimertinib is indefinite and that it is distinct from the adjuvant setting where it's being given for three years and then stopped. But I think all of us had some pause when we saw that after three years, especially in the stage III patients from ADAURA, that there were clearly an increase in recurrences after stopping the drug, suggesting that there are patients who are not cured with a time limited treatment, or at least with 3 years of treatment.  The other thing that is sobering from the study, and was pointed out by the discussant, Dr. Lecia Sequist, is if you look at the two-year disease-free survival in the placebo arm, it was only 13%, meaning almost no one was really cured with chemo radiation alone. And that really suggests that this is not that different from a very early stage IV population where indefinite treatment really is the standard of care. I wonder whether you think that's a reasonable approach. Dr. Vamsi Velcheti: I completely agree with you, Nate, and I don't think we cure a majority of our patients with stage III, and less so in patients who have EGFR-mutant, stage III locally advanced. As you just pointed out, I think very few patients actually make it that far along. And I think there's a very high rate of CNS micrometastatic disease or just systemic micrometastatic disease in this population that an effective systemic therapy of osimertinib can potentially have long term outcomes. But again, we perhaps don't cure a vast majority of them. I think that the next wave of studies should incorporate ctDNA and MRD-based assays to potentially identify those patients who could potentially go off osimertinib at some point. But, again, outside of a trial, I would not be doing that. But I think it's definitely an important question to ask to identify de-escalation strategies with osimertinib. And even immunotherapy for that matter, I think we all know that not all patients really require years and years of immunotherapy. They're still trying to figure out how to use immunotherapy in these post-surgical settings, using the MRD to de-escalate adjuvant therapies. So I think we have to have some sort of strategy here. But outside of a clinical trial, I will not be using those assays here to cite treatments, but certainly an important question to ask.  Moving on to the other exciting late-breaking abstracts, LBA5, the ADRIATIC study. This is another study which was also in the plenary session. This study was designed to address this question of consolidation immunotherapy, post chemo radiation for limited-stage small cell cancer, the treatment arms being durvalumab tremelimumab, and durvalumab observation. So what do you think about the study? This study also received a lot of applause and a lot of attention at the ASCO meeting. Dr. Nate Pennell: It was. It was remarkable to be there and actually watch this study as well as the LAURA study live, because when the disease free survival curves and in the ADRIATIC study, the overall survival curves were shown, the speakers were both interrupted by standing ovation of applause just because there was a recognition that the treatment was changing kind of before our eyes. I thought that was really neat. So in this case, I think this is truly a historic study, not necessarily because it's going to necessarily be an earth shakingly positive study. I mean, it was clearly a positive study, but more simply because of the disease in which it was done, and that is limited-stage small cell lung cancer. We really have not had a change in the way we've treated limited-stage small cell lung cancer, probably 25 years. Maybe the last significant advances in that were the advent of concurrent chemotherapy and radiation and then the use of PCI with a very modest improvement in survival. Both of those, I would say, are still relatively modest advances.  In this case, the addition of immunotherapy, which we know helps patients with small cell lung cancer - it's of course the standard of care in combination chemotherapy for extensive stage small cell lung cancer - in this case, patients who completed concurrent chemo radiation were then randomized to either placebo or durvalumab, as well as the third arm of durvalumab tremelimumab, which is not yet been recorded, and co primary endpoints were overall survival and progression free survival. And extraordinarily, there was an improvement in overall survival seen at the first analysis, with a median overall survival of 55.9 months compared to 33.4 months, hazard ratio of 0.73. So highly clinically and statistically significant, that translates at three years to a difference in overall survival of 56.5%, compared to 47.6%, or almost 10% improvement in survival at three years.  There was also a nearly identical improvement in progression-free survival, also with a hazard ratio of 0.76, suggesting that there's a modest number of patients who benefit. But it seems to be a clear improvement with the curves plateauing out. In my opinion, this is very comparable to what we saw with the PACIFIC study in stage III, unresectable non-small cell lung cancer, which immediately changed practice back when that first was reported. And I expect that this will change practice pretty much immediately for small cell as well. Dr. Vamsi Velcheti: Yeah, I completely agree, Nate. I think it's an exciting advance in patients with limited-stage small cell lung cancer. For sure, it's practice-changing, and I think the results were exciting.  So one thing that really intrigued me was in the extensive-stage setting, the benefit was very mediocre with one-to-two month overall survival benefit in both the PACIFIC and in IMpower trial. Here we are seeing almost two-year of median OS benefit. I was kind of puzzled by that, and I thought it may have to do with patients receiving radiation. And we've seen that with the PACIFIC, and makes you wonder if both the CASPIAN and the IMpower studies actually did not allow consolidation thoracic radiation. Hypothetically, if they had allowed consolidation thoracic radiation, perhaps we would have seen better outcomes. Any thoughts on that? Dr. Nate Pennell: We've been trying to prove that radiation and immunotherapy somehow go together better for a long time. Going back to the first description of the abscopal effect, and I'm not sure if I necessarily believe that to be the case, but in this setting where we truly are trying to cure people rather than merely prolong their survival, maybe this is the situation where it truly is more beneficial. I think what we're seeing is something very similar to what we're seen in PACIFIC, where in the stage IV setting, some people have long term survival with immunotherapy, but it's relatively modest. But perhaps in the curative setting, you're seeing more of an impact. Certainly, looking at these curves, we'll have to see with another couple of years to follow up. But a three-year survival of 56% is pretty extraordinary, and I look forward to seeing if this really maintains over the next couple of years follow up.  Moving beyond the Plenary, there were actually lots of really exciting presentations, even outside the Plenary section. One that I think probably got at least as much attention as the ones that we've already discussed today was actually an update of an old trial that's been presented for several prior years. And I'm curious to get your take on why you thought this was such a remarkable study. And we're talking about the LBA8503, which was the 5-year update from the CROWN study, which looked at previously untreated ALK-positive advanced non-small cell in cancer patients randomly assigned to lorlatinib, the third generation ALK inhibitor, versus crizotinib, the first generation ALK inhibitor. What was so exciting about this study, and why were people talking about it?  Dr. Vamsi Velcheti: Yeah, I agree, Nate. We've seen the data in the past, right? Like on the CROWN data, just first like a quick recap. This is the CROWN study, like the phase 3 study of third generation ALK inhibitor lorlatinib. So global randomized phase 3 study in patients with metastatic disease randomized to lorlatinib versus crizotinib, which is a controller. So the primary endpoint was PFS, and we've seen the results in the past of the CROWN readout quoted, with a positive study and the lorlatinib received FDA approval in the frontline setting. But the current study that was presented at the ASCO annual meeting is a kind of a postdoc analysis of five years. The endpoint for the study with central review stopped at three years, and this is actually a follow up beyond that last readout. Interestingly, in this study, when they looked at the median PFS at five years, the lorlatinib arm did not reach a median PFS even at five years and the hazard ratio is 0.19, which is kind of phenomenal in some ways. At 5 years, the majority of the patients were still on the drug. So that's quite incredible. And the benefit was more profound in patients with brain mets with a hazard ratio of 0.08. And again, speaking to the importance of brain penetrant, small molecule inhibitors, and target therapy, the safety profile, there were no additional safety signals noted in the study. We kind of know about the side effects of lorlatinib already from previous studies readouts. No unusual long-term toxicities.  I should note though, about 40% of patients did have CNS, AEs grade 1, 2 CNS toxicities on the  lorlatinib arm. And the other interesting thing that was also reported in the trial was dose reduction of lorlatinib did not have an impact on the PFS, which is interesting in my opinion. They also did some subgroup analysis, biomarker testing, biomarker populations. Patients who had P53 cooperation did much better with lorlatinib versus crizotinib. So overall, the other thing that they also had shown on the trial was the resistance mechanisms that were seen with lorlatinib were very different than what we are used to seeing with the earlier generation ALK inhibitors. The majority of the patients who develop resistance have bypass mechanisms and alterations in MAP kinase pathway PI3K/MTOR/PTEN pathway, suggesting that lorlatinib is a very potent ALK inhibitor and on target ALK mutations don't happen as frequently as we see with the earlier generation ALK inhibitors.  So I think this really begs the question, should we offer lorlatinib to all our patients with metastatic ALK-positive tumors? I think looking at the long-term data, it's quite tempting to say ‘yes', but I think at the same time we have to take into consideration patient safety tolerability. And again, the competitor arm here is crizotinib. So lorlatinib suddenly seems to be, again, cross trial comparisons, but I think the long-term outcomes here are really phenomenal. But at the same time, I think we've got to kind of think about patient because these patients are on these drugs for years, they have to live with all the toxicities. And I think the patient preferences and safety profile matters in terms of what drug we recommend to patients. Dr. Nate Pennell: I completely agree with you. I think the right answer, is that this has to be an individual discussion with patients. The results are incredibly exciting. I mean, the two-year progression free survival was 70%, and the five-year, three years later is still 60%. Only 10% of people are failing over the subsequent three years. And the line is pretty flat. And as you said, even with brain metastases, the median survival is in reach. It's really extraordinary. Moreover, while we do talk about the significant toxicities of lorlatinib, I thought it was really interesting that only 5% of people were supposedly discontinued the drug because of treatment related AEs, which meant that with dose reduction and management, it seems as though most patients were able to continue on the drug, even though they, as you mentioned, were taking it for several years.  That being said, all of us who've had experience with the second-generation drugs like alectinib and brigatinib, compared to the third-generation drug lorlatinib, can speak to the challenges of some of the unique toxicities that go along with it. I don't think this is going to be a drug for everyone, but I do think it is now worth bringing it up and discussing it with the patients most of the time now. And I do think that there will be many people for whom this is going to be a good choice, which is exciting. Dr. Vamsi Velcheti: Absolutely, completely agree. And I think there are newer ALK inhibitors in clinical development which have cleaner and better safety profiles. So we'll have to kind of wait and see how those pan out.  Moving on to the other exciting abstract, LBA8509, the KRYSTAL-12 study. LBA8509 is a phase 3 study looking at adagrasib versus docetaxel in patients with previously treated advanced metastatic non-small cell cancer with KRASG12C mutation. Nate, there's been a lot of hype around this trial. You've seen the data. Do you think it's practice-changing? How does it differentiate with the other drug that's already FDA approved, sotorasib?  Dr. Nate Pennell: Yeah, this is an interesting one. I think we've all been very excited in recent years about the identification of KRASG12C mutations as targetable mutations. We know that this represents about half of KRAS mutations in patients with non-small cell lung cancer, adenocarcinoma, and there are two FDA-approved drugs. Sotorasib was the first and adagrasib shortly thereafter. We already had seen the CodeBreaK 200 study, which was a phase 3 study of sotorasib versus docetaxel that did modestly prolong progression free survival compared to docetaxel, although did not seem to necessarily translate to an improvement in overall survival. And so now, coming on the heels of that study, the KRYSTAL-12 study compared adagrasib, also the KRASG12C  inhibitor versus docetaxel and those with previously treated non-small cell with KRASG12C. And it did significantly improve progression free survival with a hazard ratio of 0.58. Although when you look at the median numbers, the median PFS was only 5.5 months with the adagrasib arm compared to 3.8 months with docetaxel. So while it is a significant and potentially clinically significant difference, it is still, I would say a modest improvement.   And there were some pretty broad improvements across all the different subgroups, including those with brain metastases. It did improve response rate significantly. So 32% response rate without adagrasib, compared to only 9% with docetaxel. It's about what you would expect with chemotherapy. And very importantly, in this patient population, there was activity in the brain with an intracranial overall response rate among those who had measurable brain metastases of 40%. So certainly important and probably that would distinguish it from drugs like docetaxel, which we don't expect to have a lot of intracranial toxicity. There is certainly a pattern of side effects that go along with that adagrasib, so it does cause especially GI toxicity, like diarrhea, nausea, vomiting, transaminitis. All of these were actually, at least numerically, somewhat higher in the adagrasib arm than in docetaxel, a lot more hematologic toxicity with the docetaxel. But overall, the number of serious adverse events were actually pretty well matched between the two groups. So it wasn't really a home run in terms of favorable toxicity with that adagrasib.  So the question is: “In the absence of any data yet on overall survival, should this change practice?” And I'm not sure it's going to change practice, because I do think that based on the accelerated approval, most physicians are already offering the G12C inhibitors like sotorasib and adagrasib, probably more often than chemotherapy, I think based on perceived improvement in side effects and higher response rates, modestly longer progression-free survival, so I think most people think that represents a modest improvement over chemotherapy. And so I think that will continue. It will be very interesting, however, when the overall survival report is out, if it is not significantly better, what the FDA is going to do when they look at these drugs.  Dr. Vamsi Velcheti: Thanks so much. Very well summarized. And I do agree they look more similar than dissimilar. I think CodeBreaK-200 and the KRYSTAL-12, they kind of are very identical. I should say, though I was a little surprised with the toxicity profile of adagrasib. It seemed, I mean, not significantly, but definitely seemed worse than the earlier readouts that we've seen. The GI tox especially seems much worse on this trial. I'm kind of curious why, but if I recall correctly, I think 5% of the patients had grade 3 diarrhea. A significant proportion of patients had grade 3 nausea and vomiting. And the other complicating thing here is you can't use a lot of the antiemetics because of the QT issues. So that's another problem. But I think it's more comparable to sotorasib, in my opinion.  Dr. Nate Pennell: While this is exciting, I like to think of this as the early days of EGFR, when we were using gefitinib and erlotinib. They were certainly advances, but we now have drugs that are much more effective and long lasting in these patients. And I think that the first-generation inhibitors like sotorasib and adagrasib, while they certainly benefit patients, now is just the beginning. There's a lot of research going on, and we're not going to talk about some of the other abstracts presented, but some of the next generation G12C inhibitors, for example, olomorasib, which did have also in the same session, a presentation in combination with pembrolizumab that had a very impressive response rate with potentially fewer side effects, may end up replacing the first generation drugs when they get a little bit farther along. And then moving on to another one, which I think potentially could change practice. I am curious to hear your take on it, was the LBA8505, which was the PALOMA-3 study. This was interesting in that it compared two different versions of the same drug. So amivantamab, the bispecific, EGFR and MET, which is already approved for EGFR exon 20 non-small cell lung cancer, in this case, in more typical EGFR-mutated non-small cell lung cancer in combination with osimertinib with the intravenous amivantamab, compared to the subcutaneous formulation of amivantamab. Why would this be an important study? Dr. Vamsi Velcheti: I found this study really interesting as well, Nate. And as you know, amivantamab has been FDA approved for patients with exon 20 mutation. And also, we've had, like two positive readouts in patients with classical EGFR mutations. One, the MARIPOSA study in the frontline setting and the MARIPOSA-2, in the second-line post osimertinib setting. For those studies, the intravenous amivantamab was used as a treatment arm, and the intravenous amivantamab had a lot of baggage to go along with it, like the infusion reactions and VTEs and other classic EGFR related toxicity, skin toxicities. So the idea behind developing the subcutaneous formulation of amivantamab was mainly to reduce the burden of infusion, infusion time and most importantly, the infusion related reactions associated with IV formulation.  In a smaller phase 2 study, the PALOMA study, they had looked at various dosing schemas like, subcutaneous formulation, and they found that the infusion related reactions were very, very low with the subcutaneous formulation. So that led to the design of this current study that was presented, the PALOMA-3 study. This was for patients who had classical EGFR mutations like exon 19, L858R. The patients were randomized 1:1 to subcutaneous amivantamab with lazertinib versus IV amivantamab plus lazertinib. The endpoints for the study, it's a non-inferiority study with co primary endpoints of C trough and C2 AUC, Cycle 2 AUC. They were looking at those pharmacological endpoints to kind of demonstrate comparability to the IV formulation. So in this study, they looked at these pharmacokinetic endpoints and they were essentially identical. Both subcutaneous and IV formulations were compatible. And in terms of clinical efficacy as well, the response rate was identical, no significant differences. Duration of response was also identical. The PFS also was comparable to the IV formulation. In fact, numerically, the subcutaneous arm was a little better, though not significant. But it appears like, you know, the overall clinical and pharmacological profile of the subcutaneous amivantamab was comparable. And most interestingly, the AE profile, the skin toxicity was not much different. However, the infusion reactions were substantially lower, 13% with the subcutaneous amivantamab and 66% with IV amivantamab. And also, interestingly, the VTE rates were lower with the subcutaneous version of amivantamab. There was still a substantial proportion of patients, especially those who didn't have prophylactic anticoagulation. 17% of the patients with the subcutaneous amivantamab had VTE versus 26% with IV amivantamab. With prophylaxis, which is lower in both IV and subcutaneous, but still subcutaneous formulation at a lower 7% versus 12% with the IV amivantamab.  So overall, I think this is an interesting study, and also the authors had actually presented some interesting data on administration time. I've never seen this before. Patients reported convenience using a modified score of patient convenience, essentially like patients having to spend a lot of time in the infusion site and convenience of the patient getting the treatment. And it turns out, and no surprise, that subcutaneous amivantamab was found to be more convenient for patients.  So, Nate, I want to ask you your take on this. In a lot of our busy infusion centers, the time it takes for those patients to get the infusion does matter, right? And I think in our clinic where we are kind of fully booked for the infusion, I think having the patients come in and leave in 15, 20 minutes, I think it adds a lot of value to the cancer center operation.  Dr. Nate Pennell: Oh, I completely agree. I think the efficacy results were reassuring. I think the infusion related reaction difference, I think is a huge difference. I mean, I have given a fair amount of amivantamab, and I would say the published IRR rate of 66%, 67% I would say, is maybe even underestimates how many patients get some kind of reaction from that, although it really is a first dose phenomenon. And I think that taking that down to 13% is a tremendous advance. I think fusion share time is not trivial as we get busier and busier. I know our cancer center is also very full and it becomes challenging to schedule people, and being able to do a five-minute treatment versus a five-hour treatment makes a big difference for patients.  It's interesting, there was one slide that was presented from an efficacy standpoint. I'm curious about your take on this. They showed that the overall survival was actually better in the subcu amivantamab arm, hazard ratio of 0.62. Now, this was only an exploratory endpoint. They sort of talk about perhaps some rationale for why this might be the case. But at the very least, I think we can be reassured that it's not less effective to give it and does seem to be more tolerable and so I would expect that this hopefully will be fairly widely adopted. Dr. Vamsi Velcheti: Yeah, I agree. I think this is a welcome change. Like, I think the infusion reactions and the resources it takes to get patients through treatments. I think it's definitely a win-win for patients and also the providers.  And with that, we come to the conclusion of the podcast. Nate, thank you so much for the fantastic insights today. Our listeners will find all the abstracts discussed today in the transcripts of the episode. Thank you so much for joining us today, Dr. Pennell.  Dr. Nate Pennell: Oh, thanks for inviting me. It's always fun to talk about all these exciting advances for our patients. Dr. Vamsi Velcheti: Thanks to our listeners for your time today. You will find links to all the abstracts discussed today in the transcript of the episode. Finally, if you value the insights that you hear from ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcast.   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.   Find out more about today's speakers:    Dr. Vamsi Velcheti  @VamsiVelcheti    Dr. Nathan Pennell  @n8pennell    Follow ASCO on social media:      @ASCO on Twitter    ASCO on Facebook    ASCO on LinkedIn      Disclosures:  Dr. Vamsi Velcheti:  Honoraria: ITeos Therapeutics  Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen, Elevation Oncology, Taiho Oncology, Merus  Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline  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

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 voice of the world's oncology professionals.  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. Guests' statements on this 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. Cancer research discussed in this podcast is ongoing, so data described here may change as research progresses. In this podcast, Cancer.Net Associate Editor for Lung Cancer, Dr. Charu Aggarwal, and Cancer.Net Specialty Editor for Thymoma, Dr. Ryan Gentzler, discuss what people with early-stage non-small cell lung cancer should know about their treatment options before and after surgery, called neoadjuvant therapy and adjuvant therapy, respectively. Dr. Aggarwal is the Leslye Heisler Associate Professor of Medicine in the Hematology-Oncology Division at the University of Pennsylvania's Perelman School of Medicine. Dr. Gentzler is a thoracic medical oncologist and Associate Professor of Medicine in the Division of Hematology/Oncology at the University of Virginia (UVA) Comprehensive Cancer Center. View disclosures for Dr. Aggarwal and Dr. Gentzler at Cancer.Net.  To begin, Dr. Gentzler will discuss what people with early-stage non-small cell lung cancer should know about neoadjuvant treatment options before lung surgery. Welcome, Dr. Gentzler. Dr. Gentzler: Hi, this is Ryan Gentzler from the University of Virginia. We're here to discuss the role of neoadjuvant chemotherapy and immunotherapy for the treatment of locally advanced non-small cell lung cancer. So first, I thought I'd address some of the data and definition of what is neoadjuvant treatment. So when we think about treating lung cancer that is not metastatic, that is earlier stage disease, there typically involves multimodality treatment. Sometimes these lesions or tumors can be very small and can be stage I and treated with surgery alone or perhaps radiation alone and no further treatment is needed. But the vast majority of lung cancers that are considered early stage are in fact either larger tumors, involve lymph nodes, and typically fall into the category of stage II or III lung cancers. And these are cancers that often require multiple treatments beyond the local surgery approach alone. When we think about how we deliver that treatment, it can either be given before surgery or after a surgery. If we give treatment before a surgery, we call that neoadjuvant. If it is given after the surgery, we call that adjuvant. And most of the data that we have today in lung cancer uses one or the other of these approaches, and we don't typically give treatments both before and after, at least in terms of the chemotherapy part of that treatment. Historically, most of the data exists in the adjuvant treatment of lung cancer going back several decades that showed that the benefit of chemotherapy after a surgery, particularly for those with stage II and stage III lung cancer, derived a clear benefit of survival by giving chemotherapy after surgery. More recently, with the advent of immune therapy, which we have used in patients with stage IV lung cancer as well as those with stage III lung cancer who cannot undergo surgery, those immunotherapy drugs have been shown to improve overall survival and improve clinical outcomes for a wide range of patients with more advanced disease. And so in the last 4 or 5 years, we have really looked at new trials that have added immunotherapy in what we call perioperative space, either before surgery or after surgery for those that have surgically resectable disease. I'm going to focus on the neoadjuvant approaches that we have seen today, and this largely all started with data from Patrick Forde out of Johns Hopkins and Jamie Chaft from Memorial Sloan Kettering looking at single agent treatment with nivolumab immunotherapy. This was no chemotherapy given for 3 treatments prior to or three cycles prior to surgery. And that trial demonstrated a high degree of patients with tumor reduction and more importantly, we saw that the pathologic response, meaning how much tumor was left under the microscope at the time of surgery, was higher than what anyone anticipated with just immunotherapy alone. That launched a whole series of larger randomized prospective trials evaluating largely the combination of chemotherapy and immune therapy prior to surgery. Now, before we get into some of the results of these trials, I really wanted to emphasize some of the theoretical advantages to neoadjuvant approach. Now, the first potential advantage of giving neoadjuvant treatment is that we know when you start with immunotherapy and chemotherapy regimens and that's the first type of treatment, everyone is guaranteed to get that treatment. And we know that the completion rate prior to surgery is higher than it is after surgery. These patients can get all of the prescribed treatment and will be more likely to get it than if they get it after surgery. So this is one advantage. The other is potentially starting these medications which go throughout the body and treat the cancer, wherever it may be, earlier. We know that one of the risks of all cancers, but lung cancer in particular, is that even with good surgery and removing all of that cancer, there is a chance that there are cancer cells left behind, which leads to risk of recurrence in the years to come after surgery. Naturally, if we start the treatment that can eliminate those cancer cells, wherever they may be, and do that first, perhaps we catch this earlier with fewer cells that have escaped and have a more likely chance of success of eliminating the cancer and resulting in a cure. The third, I think, is one that we still have yet to learn more about, but if we give immunotherapy in particular, these are medications that activate the immune system, particularly the type of immune system cell called a T cell. If that T cell is able to recognize tumor cells, it is more likely to be able to continue to attack those tumor cells. And if we give that treatment prior to removal of the tumor, perhaps that activates the immune system in a more robust way that it can go after these cancer cells and eliminate those that are left behind after the surgery. If you give the immunotherapy after a surgery and the bulk of the tumor, most of the cancer cells have been removed, it may be harder to find those antigens or foreign proteins that are expressed in cancer cells. So the immune system may not be as robustly able to go after cancer if you give it solely after a surgery. Another potential advantage of neoadjuvant approaches is that it really helps us learn as oncologists how well a cancer is responding to a treatment. If we give these treatments for 4 cycles after a surgery, we don't know whether it's eliminating those residual cancer cells or whether it is totally ineffective. If we give it before a surgery and we see that there is tumor reduction or that there is a complete elimination of the cancer, we know that that treatment was an effective treatment at attacking the cancer cells and eliminating them. We know that the cancer was sensitive to that treatment. We can then better prognosticate how well the patients are going to do after surgery. We know based on the latest data that if you achieve what we call a pathologic complete response with chemotherapy and immunotherapy prior to surgery, meaning there are no cancer cells left when we look at that surgical specimen under the microscope, we know that those patients have a much better likelihood of surviving for longer periods of time than those who have active cancer at the time of surgery after prior treatment. And so neoadjuvant approaches allow us in a 2-month time frame to get a great sense of how well our treatments are working and able to prognosticate outcomes based on how well those cancer cells have been eliminated at the time of surgery. One large phase 3 trial called the CheckMate 816 trial was a randomized phase 3 trial and that enrolled patients with stage IB through IIIA non-small cell lung cancer using the old staging system of the 7th edition. These would all now be categorized as stage II and stage III non-small cell lung cancer patients. And it randomized these patients to 3 cycles of chemotherapy plus nivolumab, which is an immunotherapy drug, and compared that to patients treated with chemotherapy alone for 3 cycles. After these 3 cycles of chemotherapy, which is about a 9-week time frame, patients had surgical resection of their tumors. And then after surgery, patients received no further treatment, although treating physicians were allowed to give additional treatments like chemotherapy or radiation if they thought it would be beneficial for these patients, although it was not mandated by the study. One of the first results we saw from this study was that there was a much higher rate of pathologic complete response of 24% of patients achieving a path CR [pathologic complete response] with the nivolumab plus chemotherapy combination compared to only 2.2% with chemotherapy alone. This was highly statistically significant and demonstrated a clear benefit for those receiving the immunotherapy. The other main endpoint of this study was event-free survival, meaning that the time that the patients were alive and without any significant event like cancer progression or death after the enrollment of the trial. And in this analysis, the median event-free survival was significantly longer in those who have received the immunotherapy plus chemotherapy combination prior to surgery. One of the potential concerns about neoadjuvant treatment is that it may render patients unfit for surgery who otherwise could have had their cancer removed. When we look at the outcomes from this CheckMate 816 trial, it actually did not appear to be the case to a large degree. In fact, those that got the nivolumab plus chemotherapy combination were more likely to proceed on with surgery, and the majority did; 83% received the planned surgery. There were patients who were unable to receive surgery due to adverse events of their treatment, but that was only 1% of patients enrolled in the trial. Other reasons for canceling the surgery included disease progression, meaning the cancer got worse to the point where they could not undergo surgery, or other reasons, such as the patient declined surgery, or it was found to be unresectable at the time the surgeon wanted to remove the cancer, or poor lung function.   One of the insights we got from the surgical data from this trial were that those who received the combination of chemotherapy and immunotherapy had slightly higher rates of smaller surgeries like a lobectomy compared to a pneumonectomy for those who had received [chemotherapy alone.] There were also fewer numbers of patients who required a conversion from a minimally invasive surgical procedure to an open surgical procedure if they were getting the immunotherapy combination. A higher number of patients also were able to have complete resection of their tumor if they received the immunotherapy/chemotherapy combination. The length of hospitalization was slightly lower, and the rates of pain were slightly lower in those who received the combination as well. These comparisons were not statistically significantly different, but numerically, there seems to be at least a trend toward benefit in surgical outcomes in this neoadjuvant chemotherapy/immunotherapy approach. And I think this makes sense. We know that this combination is more able to eliminate a cancer and make it a pathologic complete response when we look at it under the microscope, and therefore, if there is shrinking the tumor to a higher degree, naturally, it seems there would be more likely of completely removing the tumor, using a smaller incision to remove that tumor, shortening the length of stay in the hospital and recovery time and pain control. All makes sense if we know that the treatment itself is able to reduce that size of the tumor. There are many other phase 3 trials ongoing studying the impact of immunotherapy plus chemotherapy in the neoadjuvant setting. The AEGEAN trial has recently reported data at the AACR meeting this year in 2023 with similar results that we saw with the CheckMate 816 trial. There are 3 other phase 3 trials that are ongoing, one of which we will see later this summer called the KEYNOTE-671 trial evaluating pembrolizumab plus chemotherapy in the neoadjuvant setting and then 2 other trials evaluating nivolumab, the CheckMate 77T trial, or atezolizumab in the IMpower030 trial. Each of these more recent trials typically have used 4 cycles of chemotherapy plus immunotherapy prior to surgery and also continued the immunotherapy after surgery for a period of time, most commonly approximately 1 year. From the data we have seen so far, it remains uncertain whether additional immunotherapy beyond the 3 or 4 cycles given in the neoadjuvant setting provides any additional benefit. We still do not understand what to do with patients who did not achieve a pathologic response whether further treatment would be of any additional benefit. We do not know if there will be further benefit even in those that achieved a pathologic complete response whether a slightly longer duration of immunotherapy would further improve outcomes in that group. We suspect with longer-term follow-up over the years of all of these phase 3 trials that some of these questions will be answered. So what are some key questions that patients should ask when considering a neoadjuvant chemotherapy/immunotherapy approach? I think the first question that's key is what is my tumor stage? We know that the trials that enrolled patients with a neoadjuvant approach enrolled patients using our current staging system would be a stage II or stage III lung cancer. And this is where it gets really tricky is, what subdivision of stage III is it? We tend to think of stage IIIA's as being one that it would be surgically resectable, with a smaller number of stage IIIBs, and then stage IIIC, one that we would not typically recommend surgery for. I think the next question within the tumor stage is, is this based on imaging or based on the biopsies? And we know that biopsies are really the best way to stage locally advanced cancers, particularly getting samples of lymph nodes in the mediastinum. Sometimes what looks like a stage I or stage II on imaging is, in fact, a stage III based on biopsies that are done at the time of surgery. It's ideal to know that information prior to making the decision about surgery so that that surgery is not futile.   On the opposite side, sometimes there is imaging suggestive of lymph nodes that are enlarged in the mediastinum, and it's presumed that this is a more advanced stage III and is not surgically resectable. However, if you go and biopsy those lymph nodes, sometimes they are benign. Sometimes they are inflammation related to infection or cancer but do not actually contain cancer cells. And so we typically advise that getting biopsies of lymph nodes in the mediastinum, at least any that are particularly suspicious, is highly recommended for these locally advanced cancers. I think the next question that's key to ask is, what are my tumor biomarkers? And there are multiple biomarkers that we look at in non-small cell lung cancer that help us decide what is the best treatment. What is the best approach? What is the best medicine to treat the cancer? We know that one of these biomarkers that is a key is a mutation. So multiple different mutations can occur in lung cancers, particularly those that are adenocarcinoma subtypes. And these mutations may be less likely to benefit from immunotherapy and we may want to take a different approach with surgery, chemotherapy, and potentially targeted therapies that specifically target that mutation that exists in the tumor. The other key biomarker here is PD-L1. We know that tumors with a higher level of PD-L1 are more likely to respond and benefit from immunotherapy. As of right now, that PD-L1 status plays a more important role in the adjuvant setting. All of the chemotherapy plus immunotherapy combinations in the neoadjuvant setting seem to benefit the group as a whole regardless of that PD-L1 status. But still, an important biomarker that we should have prior to making all final decisions on treatment. I think another question that should be asked any time you have an earlier stage cancer is, is my tumor surgically resectable? And there can be many reasons why cancers are not resectable, perhaps due to the anatomy of where the tumor is located, if it invades into the mediastinum, for example, or is near large blood vessels, or perhaps because there are too many lymph nodes and this is a more advanced stage. And so I think the main reasons for not being surgically resectable would be the tumor is too large, if the stage is too high, or is it more of a function of fitness for surgery and that can be because of other underlying lung disease. Perhaps removing part or all of a lung would not be safe due to impaired lung function to begin with. And I think it's important to understand that sometimes stage III lung cancers are resectable and sometimes they are not, and understanding the reason why they are not, I think, is important. And then I think lastly and ultimately when we're talking about a neoadjuvant approach, you want to ask your treating oncologist, "Would it be better to give my treatment before surgery or after surgery?" And really discuss the pros and cons with the physician and have them incorporate all of the factors that go into these treatment decisions. How well you'll tolerate chemotherapy, other medical conditions that may play a role in the likeliness of getting through those treatments safely, perhaps underlying diseases that may increase the risk of immune-related side effects with immunotherapy. You really want to factor in all of these things and discuss the pros and cons of a systemic treatment first versus surgery first before making final decisions on how to treat locally advanced lung cancer. All right. Thank you. ASCO: Thank you, Dr. Gentzler. Next, Dr. Aggarwal will discuss what people with early-stage non-small cell lung cancer should know about their adjuvant treatment options for after lung surgery.   Dr. Aggarwal: This is Dr. Charu Aggarwal. I'm the Leslye Heisler Associate Professor for Lung Cancer Excellence at University of Pennsylvania's Abramson Cancer Center. And today I will talk to you about the use of adjuvant immunotherapy in the setting of early-stage non-small cell lung cancer. We'll start by discussing what adjuvant therapy is, what types of options we have for adjuvant therapy, what kind of testing is important, and what options there may be in terms of adjuvant immunotherapy. So let's get started. Early-stage lung cancer comprises of stages between stage I to stage III. These stages vary by the size of the tumor as well as the level of lymph node involvement. In the setting of very early-stage lung cancer, such as stage I and stage II, as well as some select stage III lung cancers, we recommend surgical resection. And in these patients, the use of additional treatment is recommended based upon the pathological determination of the tumor size as well as the lymph node status. If usually lymph nodes are involved, we recommend adjuvant chemotherapy, and also, many experts will deliver adjuvant chemotherapy for tumors that may be larger than 4 centimeters even in the absence of lymph node involvement. The data for adjuvant chemotherapy comes from several large clinical trials that were conducted about a couple of decades ago now that demonstrated not only an improvement in preventing recurrence of the cancer but also a modest improvement in overall survival, really laying the ground for improvement and therefore becoming the gold standard. Four cycles of chemotherapy are usually administered about 6 to 12 weeks following surgical resection, and this is really the basis of our treatment in the early-stage setting. In today's time and age, we now have several other options. We have treatment options that include molecular therapy, which is biomarker driven, as well as the use of immunotherapy. So it's actually very important for us in the adjuvant setting--or in the post-surgical setting--to test for mutations such as EGFR. It's also important for us to test PD-L1 status. So let's dive into why each of these may be important. Patients with EGFR mutations, especially those with sensitizing mutations in EGFR exon 19 or 21, now have the opportunity to receive a targeted therapy in the form of osimertinib, which is an oral drug, very targeted and specific for the EGFR mutation that has been studied in a clinical trial setting in patients with early-stage non-small cell lung cancer. In patients with stage IB to IIIA non-small cell lung cancer with EGFR mutation, use of osimertinib was associated with a significant improvement in our ability to delay the recurrence of cancer. Based on this significant improvement, FDA approved therapy with osimertinib, and it is currently available and ready to use. We usually recommend it for 3 years, so daily therapy for 3 years, and patients are monitored with routine CAT scans and lab work. For patients who don't have an EGFR mutation, we do recommend broad panel testing. Of course, this is not the standard, but I think it's important for us to identify patients who may not benefit from immunotherapy. Patients that have an ALK mutation, for example, or ROS1 translocation, may not have the best chances of responding to adjuvant immunotherapy, and therefore, I think testing should be performed to make sure that we are having a shared decision-making conversation with our patients about the use of the correct adjuvant options. In terms of adjuvant immunotherapy, we now have 2 approved agents. One of them is atezolizumab, and the other one that was just recently approved is pembrolizumab. Atezolizumab was approved on the basis of a large clinical trial called the IMpower010 study, which randomized 1,280 patients with stage IB to IIIA non-small cell lung cancer to either 1 year of atezolizumab or best supportive care. Of note, all of these patients had to have had adjuvant chemotherapy that included a cisplatin platinum chemotherapy. In the first analysis, we found that the disease-free survival or the probability of the patients remaining cancer-free was significantly improved in those patients that had a tumor expression of PD-L1 greater than or equal to 1% and received atezolizumab compared to patients who did not receive atezolizumab. On the basis of this positive primary endpoint, the U.S. FDA approved the use of adjuvant atezolizumab for patients with stage II to IIIA resected non-small cell lung cancer after surgical resection and adjuvant chemotherapy. Recently, we heard that this does lead to small but significant improvement in overall survival. There is a trend towards improvement in overall survival. However, the data are quite immature at this point, and we do need longer follow-up to be able to follow this trend. The greatest magnitude of overall survival benefit was found in patients who had the PD-L1 greater than or equal to 50%. So it's important to know what the PD-L1 level of a patient may be when I'm thinking about adjuvant immunotherapy because adjuvant immunotherapy is most likely to benefit those that don't have an actionable mutation, such as EGFR, and those that have the highest PD-L1 staining, at least in the IMpower trial. Secondly, the PEARLS clinical trial is a clinical trial that evaluated the use of pembrolizumab, which is another immunotherapy agent, again, in the adjuvant setting. For this clinical trial as well, there was a small but significant improvement in disease-free survival, again preventing the probability of recurrence in all patients that received pembrolizumab compared to the best supportive care. And basically, this led to also an approval by the FDA for the use of pembrolizumab. Again, now we have 2 options. Both of these are administered for 1 year. What should patients know about therapy? These drugs are usually administered once every 3 weeks. They are given intravenously. Sometimes, we can change the treatment schedule to be either once every 4 weeks in the case of atezolizumab or every 6 weeks in the case of pembrolizumab. These may be associated with some side effects. Immunotherapy side effects that are most common are fatigue, chills, myalgias, or basically a feeling of pains in the body or joints. But also, some serious life-threatening reactions can occur such as activation of the immune system to such an extent that the immune system may start to attack the body's organs. So this may lead to swelling or inflammation in the organs that may manifest itself as colitis if the gut gets inflamed, or pneumonitis if the lungs were to get inflamed, or pancreatitis if the pancreas were to get inflamed. Any organ in the body can really get inflamed. We've certainly seen cases of thyroiditis. We've seen cases of polyarthritis. We've seen cases where the brain may also get inflamed or the pituitary may get inflamed. So there are definitely some life-threatening reactions or side effects that can occur with the use of immunotherapy that should be closely monitored. The benefit of having used immunotherapy in the metastatic setting is that now we have a lot of experience managing these side effects. And if recognized early, these side effects can be managed appropriately with the use of steroids as well as holding therapy. Many of the times, we can even reinstitute immunotherapy without significant harm to the patients. However, I think immunotherapy benefits as well as side effects should be discussed in detail with the provider, especially in the adjuvant setting. Patients may ask if neoadjuvant immunotherapy along with chemotherapy is a better approach compared to adjuvant immunotherapy. At this time, we don't have a clinical trial that is comparing neoadjuvant chemoimmunotherapy followed by surgery to an approach that is surgery followed by adjuvant immunotherapy. In general, I would say that if the decision by a multidisciplinary team has been made to proceed with surgery, careful discussion should be had about adjuvant chemotherapy as well as the use of adjuvant immunotherapy, and molecular testing should be performed. All patients with early-stage disease should have a multidisciplinary tumor board discussion, which includes engagement with surgeons, radiation oncologists, pulmonologists, pathologists, and medical oncologists so that they can ensure that many experts have had the chance to weigh into their case as well as come to the right conclusion on whether or not to use new adjuvant chemoimmunotherapy or just to proceed with surgical resection. ASCO: Thank you, Dr. Aggarwal. You can learn more about neoadjuvant and adjuvant treatment options for early-stage non-small cell lung cancer at www.cancer.net/lung. Cancer.Net Podcasts feature trusted, timely, and compassionate information for people with cancer, survivors, and their families and loved ones. Subscribe wherever you listen to podcasts for expert information and tips on coping with cancer, recaps of the latest research advances, and thoughtful discussions on cancer care.   And check out other ASCO Podcasts to hear the latest interviews and insights from thought leaders, innovators, experts, and pioneers in oncology.  Cancer.Net is supported by Conquer Cancer, the ASCO Foundation, which funds lifesaving research for every type of cancer, helping people with cancer everywhere. To help fund Cancer.Net and programs like it, donate at CONQUER.ORG/Donate. 

Dr. Greg Kalemkerian joins us on the ASCO Guideline Podcast to discuss the newest ASCO – Ontario Health (Cancer Care Ontario) Guideline on systemic therapy for small-cell lung cancer (SCLC). He reviews the evidence-based recommendations from the panel, including guidance on systemic therapy options for resected, limited-stage, extensive-stage, and relapsed SCLC, and NSCLC with an EGFR mutation that has transformed to SCLC, recommendations for older adults with poor performance status, the role of biomarkers, and the use of myeloid supportive agents. Dr. Kalemkerian also highlights future research for systemic therapy options for SCLC, and the impact of guidelines on both clinicians and patients with SCLC. Read the full guideline, “Systemic Therapy for SCLC: ASCO-OH (CCO) Guideline” at www.asco.org/thoracic-cancer-guidelines." TRANSCRIPT This guideline, clinical tools, and resources are available at http://www.asco.org/thoracic-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest disclosures in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO.23.01435  Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts.   My name is Brittany Harvey, and today I'm interviewing Dr. Greg Kalemkerian from the University of Michigan, co-chair on “Systemic Therapy for SCLC: American Society of Clinical Oncology – Ontario Health Guideline.” Thank you for being here, Dr. Kalemkerian.  Dr. Greg Kalemkerian: Thank you. Brittany Harvey: Before we discuss this guideline, 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 disclosures of potential conflicts of interest for the guideline panel, including Dr. Kalemkerian, who has joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes.  So then, to move into what we're here today to discuss, Dr. Kalemkerian, can you provide an overview of both the scope and the purpose of this guideline? Dr. Greg Kalemkerian: So, the guideline is meant to update the systemic treatment for small-cell lung cancer. There have been several changes in the last couple of years. For the first time in quite a few decades, we actually have some newer drugs that have demonstrated benefits in this disease. So we're really focusing on the systemic therapy. And ASCO does endorse the ASTRO guidelines for the radiotherapy involved in patients with small-cell lung cancer. Brittany Harvey: Great. That's great to hear that there's new systemic therapy options for patients with small-cell lung cancer.  So then I'd like to review the key recommendations of this guideline. This guideline reviews eight clinical questions in total, so we can go through the key points of the recommendations for each question. So let's start with what is recommended for adjuvant systemic therapy in patients with resected small-cell lung cancer? Dr. Greg Kalemkerian: So, to start with, only fewer than 5% of people have what would be considered resectable small-cell lung cancer, and that's stage I small-cell lung cancer. So tumors less than 5 cm in size without any lymph node involvement, either hilar or mediastinal lymph node involvement. So purely the very early stages, which are rare in small-cell. And if patients undergo surgical resection for such tumors, the recommendation afterward is to provide adjuvant chemotherapy with four cycles of either cis-or carboplatin plus etoposide in order to try and improve longer-term survival for those patients.  The other part of the recommendation is we do recommend that treatment be started within eight weeks of surgery. There is little data on timing in small-cell lung cancer, but that's derived from extrapolating from non-small cell lung cancer as well. Brittany Harvey: Understood. I appreciate you reviewing those recommendations for resectable small-cell lung cancer.  So then, moving along, what does the panel recommend for patients with limited-stage small-cell lung cancer? Dr. Greg Kalemkerian: So, the treatment with limited-stage small cell lung cancer unfortunately has not changed in quite some time. We recommend that patients receive four cycles of either cisplatinum or carboplatin and etoposide concurrently with radiotherapy. Preferably the radiotherapy should be given early and concurrently with the chemotherapy, though we do not recommend that people wait for the radiation to get started in order to start the chemotherapy. So we do recommend that the chemotherapy get started as soon as possible and then the radiation can be added in on the second cycle of chemotherapy. Brittany Harvey: Then to follow that up, what is recommended for patients with extensive stage small-cell lung cancer? Dr. Greg Kalemkerian: So, extensive stage small-cell lung cancer now is probably the most straightforward of the portions of this. Based on the data from two trials thus far, the IMpower 133 trial and the CASPIAN trial, we now recommend chemotherapy with immunotherapy. The chemotherapy should be cisplatinor carboplatin plus etoposide along with concurrently either atezolizumab or durvalumab as the immunotherapy for four cycles of the combined chemo-immunotherapy followed by maintenance with the immunotherapy drug of choice. With regard to the choice of either cisplatin or carboplatin, meta-analysis has demonstrated that there is no significant difference between the two and our belief is that carboplatin is likely the more reasonable drug in the palliative treatment situation based on its better non-hematologic toxicities. Brittany Harvey: Appreciate you sharing those recommendations and some of the rationale behind those.  So then moving along, what options are available for patients with relapsed small-cell lung cancer? Dr. Greg Kalemkerian: So relapsed small-cell lung cancer gets a little more potentially complicated. One of the main drivers of outcome in patients with relapsed small cell lung cancer is the time since they completed their initial chemotherapy. Patients who have had a longer time since chemotherapy do better and have better responses to subsequent therapy. For patients who relapse with a short interval within 90 days or three months of completion of prior chemotherapy, our recommendation is that they be treated with single-agent chemotherapy. There are two drugs that are currently FDA approved for use in relapsed small cell lung cancer, topotecan and lurbinectedin, and either one of those is the preferred agent as a single-agent treatment in this scenario. For people with a longer chemotherapy-free interval, so beyond the 90 days or three months, one could either use combination chemotherapy, so reinitiation or re-induction with the regimen such as carboplatin and etoposide, or one could use single-agent chemotherapy with the preferred agents being topotecan or lurbinectedin again. The use of combination chemotherapy has been shown to improve response rates in this situation over topotecan alone. However, we have not been able to demonstrate that there is a significant improvement in overall survival. So one has to look at the individual patient and make some judgment on whether you think that the added potential toxicity of combination chemotherapy is beneficial for that individual.  For people who have progression of disease while they are on maintenance therapy with immunotherapy for extensive stage small-cell lung cancer, we do not recommend continuation of the immunotherapy. So if people progress while they're on the immunotherapy, even if they're nine months out on that, then treatment with second-line chemotherapy, either with the combination agent or with single agents, would be what we would recommend, and not continuing the immunotherapy. If patients had previously been treated for limited-stage small-cell lung cancer where immunotherapy is not part of the initial treatment at this time, and they relapse, say, six months or nine months out from their initial chemotherapy and radiation therapy treatment, then it would be reasonable to perhaps initiate carboplatin etoposide and one of the immunotherapy agents as appropriate treatment, because that patient is immunotherapy naive.  However, the single-agent immunotherapy does not have a role in the treatment of patients with relapsed small-cell lung cancer.  Brittany Harvey: Understood. It sounds like some of the treatment options are individualized to the specific patient then.  So the next question also addresses specific groups of patients. So what did the panel recommend for older adults with small cell lung cancer or for those with poor performance status? Dr. Greg Kalemkerian: Approximately half of people who have small-cell lung cancer are over the age of 70 years old, so it is a disease of older smokers. Many of these people have comorbidities that can limit our ability to use standard treatments. Many of these individuals also have poor performance status because the disease is an aggressive disease that causes a lot of problems for people. So the issue of older individuals and people of poor performance status is something that we run into on a regular basis in treating people with small-cell lung cancer.  For patients with limited-stage small-cell lung cancer who are older and have a performance status of 0 to 2, it is very reasonable to utilize standard treatment with standard chemo and radiotherapy with curative intent. For people with limited-stage small-cell lung cancer who have a performance status of 3 or 4, and this would include people who might be in an ICU with an obstructive airway, then it is reasonable to initiate chemotherapy in order to try and shrink the cancer down and improve their situation. Small-cell lung cancer is a disease that is very sensitive to chemotherapy initial treatment, so many of these people will have shrinkage of tumor and improvement of their symptoms. If the poor performance status is due to the small-cell lung cancer, it has potential to get better. So we do recommend for people at limited-stage small-cell lung cancer and a poor performance status that is felt to be due to the disease, the cancer, then it is reasonable to initiate treatment with chemotherapy. And depending on the person's response and recovery and improvement in their performance status, then one could add radiotherapy later on or do it sequentially with the definitive radiotherapy for the limited-stage small-cell lung cancer.  For older individuals with extensive stage small cell lung cancer who have a performance status of 0-2, it is very reasonable to utilize the standard chemotherapy and immunotherapy as we outlined previously in treating that. For individuals who have a poorer performance status, so performance status 3 or 4, one really needs to individualize the situation. If the poor performance status is due to the cancer, then again, it would be reasonable to attempt chemotherapy in an effort to try and shrink the cancer. There is no data on the use of chemo plus immunotherapy in this patient population. But the use of standard chemotherapy, obviously, in the older individuals preferring carboplatin over cisplatinum with etoposide would be a reasonable option, taking into account abnormalities in organ function that may require dose adjustments or reductions. Because small-cell lung cancer is a disease that is quite sensitive and responds well to  chemotherapy, then one can individualize in those situations for patients with poor performance status to see if they can improve their overall situation and have some period of time of optimized quality of life. Clearly, it is a very individualized decision-making whether or not to treat these patients. That requires clearly the patient's input as well, as a primary driver of what is done.  Brittany Harvey: Absolutely. That nuance is helpful for patient-clinician shared decision-making, depending on the factors that you mentioned.  So then, switching to the next topic that the expert panel addressed, what does the panel recommend for patients with non-small cell lung cancer with an EGFR mutation that has then transformed to small-cell lung cancer?  Dr. Greg Kalemkerian: The EGFR mutant non-small cell lung cancer transformation to small-cell lung cancer is relatively rare. I think in the real world, this probably is occurring in 2%-3% of people with EGFR mutant non-small cell lung cancer, but we do see it. Now, these patients are initially being treated with EGFR inhibitor therapy for their mutant non-small cell lung cancer and then they develop a more aggressive progression of disease. It is important to note that when people progress in that situation, it is important to get a biopsy in order to see whether or not transformation has occurred and whether or not there are any other new driver mutations that might be targetable. If the patient has a small cell lung cancer transformation, then the recommendation is to treat them as we treat patients with small cell lung cancer with chemotherapy consisting of platinum and etoposide for four to six cycles, as we usually do. It does not appear that there is a role for immunotherapy in this situation, though we clearly have a paucity of data on these patients. So we do not yet have any trials that have looked at the management of this population. We do have several series that have presented these individuals and what their outcomes are with treatment. And their outcomes are very similar to people with de novo small-cell lung cancer. So not a very good situation, but we do recommend that they be treated with standard chemotherapy, platinum plus etoposide.  Another question that arises is do you continue with the targeted therapy with the EGFR inhibitor. And the honest answer is we don't know. We don't have data on that. We do know from case reports, the series, and from personal experiences, that some people, in fact, I think many people, if not most of these individuals, have a mix of both EGFR mutant adenocarcinoma and small-cell lung cancer at the time that they transform. So not every tumor in their body is transforming, so that EGFR mutant tumor is still present in their body. So even though the small-cell lung cancer component, because it's progressing, is clearly not responsive to the EGFR inhibitor any longer, the adenocarcinoma component most likely is still sensitive to the EGFR inhibitor. So it is not unreasonable to continue with the EGFR-targeted therapy along with the small cell lung cancer-directed chemotherapy. Even though we don't have any strong data supporting one way or the other. Brittany Harvey: I appreciate that guidance, even with the dearth of data in this relatively rare scenario.  So then we've talked a bit about individualized treatment, and often in that conversation, biomarkers come up. So what does the guideline say regarding the role of biomarkers for patients with small-cell lung cancer? Dr. Greg Kalemkerian: This is pretty straightforward. Thus far, in people with de novo small-cell lung cancer - so we're not talking about the transformed patients from EGFR mutant, we're talking about people who present with small-cell lung cancer - we have no evidence that molecular diagnostic testing would help guide treatment or improve patient outcomes at this time. So we do not support obtaining molecular diagnostic testing for the routine care of patients with de novo small-cell lung cancer. I would love to talk for the next half hour about what's coming down the pipeline in small-cell lung cancer with regard to identifying subsets of patients and trying to identify the vulnerabilities within those subsets of patients that may lead to better-targeted therapy based on molecular diagnostics, but in the current environment, there is no role for molecular diagnostics.  Brittany Harvey: Understood. We'll look for that in future guideline updates instead, then.  So then the last clinical question that the guideline addressed - what myeloid supportive options may be offered for patients with small cell lung cancer? Dr. Greg Kalemkerian: So this has to be couched initially with whether or not one thinks that myeloid suppressive agents are necessary in the treatment of patients with small-cell lung cancer. So in extensive-stage disease with the use of chemotherapy, say, carboplatin and etoposide, the majority of patients likely don't require myeloid supportive agents. However, if one believes that the patient, because of their own individual characteristics, or in a patient who has already developed myelosuppressive problems, then one could either utilize trilaciclib, which was FDA-approved a couple of years ago and was shown to improve the blood counts in people with small cell lung cancer treatment, or one could utilize G-CSF. So either trilaciclib or G-CSF could be utilized to support the patient's bone marrow. In patients who have limited-stage disease, for many years, we have recommended against using G-CSF in combination with chemotherapy and radiotherapy due to concerns for increasing toxicities, including thrombocytopenia. Recent data suggests that this may not necessarily be a hard and fast rule and that if one feels that the patient requires or would benefit from some myeloid support, then G-CSF may be offered to patients undergoing chemotherapy and radiotherapy. I do not think that the standard patient that we see who is starting on treatment requires such support, but some subsets of patients or patients who have already proven that they're getting into trouble with their counts, G-CSF could be utilized in this situation.  So with regard to this recommendation, overall, it's that for patients with extensive stage disease, trilaciclib or G-CSF could be used if one feels they're necessary. And for limited-stage small cell lung cancer, G-CSF could be utilized if you feel it's necessary.  Brittany Harvey: Thank you for reviewing those options and all of these recommendations. The panel was certainly hard at work reviewing the evidence and developing these recommendations.  In your view, Dr. Kalemkerian, what is the importance of this guideline for both clinicians and for patients with small-cell lung cancer? Dr. Greg Kalemkerian: Well, I think it's not just small-cell lung cancer, but when you look at guidelines overall, I think they are very important to have evidence-based guidelines as well as expert consensus-based guidelines because, quite honestly, the field is moving very quickly, the field of oncology. Now, small-cell lung cancer hasn't moved as quickly as we would like compared to other aspects of oncology, but it's very hard for the clinician who is trying to care for patients with lots of different tumor types to keep up with all of the flood of literature, the flood of new FDA approvals that are coming out every week. So I do think that utilizing the guidelines is important in order to see what the standard approach might be.  Now, I also have to couch that with saying that guidelines are never enough. We have to look at the individual sitting across the exam table from us. We have to personalize the treatment to that individual. I will say that in my own practice, there are very few people who walk in the door who are the optimal patient, who are the person who has outstanding physical function. And in lung cancer, that's even more true because patients tend to be older smokers, and they have a lot of comorbidities and other things that you have to personalize therapy towards in them. So the guidelines are a very good starting point in order to know what the optimal treatment might be and then to adjust that accordingly to the person sitting in the room with you.  Brittany Harvey: Definitely, we hope guidelines are a place that clinicians can turn to for evidence-based recommendations and succinct recommendations, but individualized patient and clinician decision-making is paramount to each of our guidelines.   So then, Dr. Kalemkerian, we've already talked about this a little bit when you mentioned molecular testing advances down the road. So maybe I'll ask what are the most pressing, unanswered questions about systemic therapy for small-cell lung cancer? Dr. Greg Kalemkerian: Yeah, so one of them I'll come back to limited-stage small-cell lung cancer. So, obviously, in the extensive stage, we've now incorporated immunotherapy. And yet I didn't talk about immunotherapy in the limited-stage setting, and neither do the guidelines because thus far we don't have any data on the use of immunotherapy in limited-stage small-cell lung cancer. We are expecting data to be coming down the line within the next year hopefully, definitely, within the next two years, because a number of trials that are either ongoing or have recently been completed looking at incorporating immune checkpoint inhibitors into the treatment of limited-stage small-cell either concurrently with chemoradiation or as consolidation after chemoradiotherapy. So that data is anxiously anticipated. And we're hoping that that might move the needle a little bit further in limited-stage small-cell lung cancer and hopefully improve that long-term survival or cure rate that we see in that disease.  Other avenues coming down the line – many of us have made a career of doing negative trials in small-cell lung cancer, myself included, and a lot of that has had to do with trying to target therapies to specific molecular abnormalities, and none of those have really panned out thus far. But coming down the line, as we start to molecularly subtype lung cancers, and the best molecular subtyping that we have thus far is not based on mutational analysis, but more based on expression, gene expression analysis, expression of particular transcriptional factors within different subsets of small cell lung cancer, we're now starting to see some vulnerabilities. So one of these subsets in the small cell lung cancer array has a high expression of DLL3, which is part of the Notch pathway, and we can target that. We haven't figured out how to target it as far as its activity goes, but we can target it as a homing device in order to get either drugs delivered by use of antibody-drug conjugates, or to use a BiTE—a T-cell engaging type molecule—that targets both DLL3and T cells in order to try and amplify that immune response in small cell lung cancers. So recently a compound called tarlatamab had data presented at ASCO and also published in JCO that shows some response, about 20-25% response, in people with relapse small cell lung cancer. These were heavily pretreated patients. So that's moving the needle a bit in favor of a specific targeted therapy. And we're hoping that will lead to further avenues to look at the vulnerabilities of different subsets and be able to develop newer targeted treatments for these diseases, trying to amplify that immunotherapy response as well.  Small cell lung cancer is a little bit of an outlier in that it does not respond well to immunotherapy compared to other tumors. Not what we expected based on the high tumor mutational burden and the aggressiveness of the disease. But we know that it does not express a lot of PD-L1. We know that it doesn't have MHC class I molecules. So there are a number of reasons why it doesn't respond, and there is work going on to try and amplify that immune response as well. So I think those three things: the use of immunotherapy in limited-stage, the development of targeted therapies based on subsets, and trying to amplify that immune response are the things that I look forward to in the next few years. Brittany Harvey: That's great to hear. We'll await the data to provide answers to those outstanding questions.  So I want to thank you so much for your work to develop these evidence-based guidelines, and thank you for sharing your perspective with me today, Dr. Kalemkerian.  Dr. Greg Kalemkerian: Thank you, Brittany. And thanks to ASCO for getting these guidelines together and getting the outstanding group of people we had to work on it and getting them out in a timely manner so they can help our patients. Brittany Harvey: And also, thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/thoracic-cancer-guidelines.  You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app available in the Apple App Store 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.  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.    

In this episode of Lung Cancer Considered, host Dr. Stephen Liu discusses the management of small-cell lung cancer using a virtual tumor board format. SCLC is an aggressive subtype of lung cancer and for patients with advanced, or extensive-stage disease, the current first-line standard of care is chemo-immunotherapy. In the US and in Europe, the approved options are platinum and etoposide with a PDL1 inhibitor: either atezolizumab based on the IMpower 133 trial or durvalumab based on the CASPIAN trial.

How do fathers honor their sons? On this Saturday's Eric and Brigitte Weekend, joining Eric is counselor, Jeff Bercaw as they continue the conversation about how fathers can better connect. The goal is to pass on a strong idea of what Biblical manhood is all about. Peace, Release, Impower. These are a few of the key words that we will be focusing on during today’s conversation.See omnystudio.com/listener for privacy information.

Confira neste episódio uma discussão sobre os resultados do estudo IMpower 150, que avaliou a combinação de quimioterapia associada a atezolizumabe e bevacizumabe frente ao uso de quimioterapia com bevacizumabe, com participação dos Drs. Mauro Zukin e William N. William. Confira também o Vídeo-MOC, com apresentação sobre o paradigma atual do tratamento do CPNPC EGFR +. mocbrasil.com/blog/videos-moc/vol13num32/

In this episode of Building sustainably: the road to net zero, Sean Hanson, Chief Executive Officer of IMPOWER Consulting, joins Chris Lavery to share how behavioural science can be the answer to solving complex social and climate problems.

Lung cancer is one of the most commonly diagnosed type of cancer and so it is fitting that we start the first of our disease-specific oncology series with this diagnosis. This week, we begin to round out our NSCLC series with the first of two episodes where we interview Dr. Jack West from City of Hope!We strongly recommend you listen to our previous episodes on early stage lung cancer (Episodes 026 and 029) to follow along in this discussion. Key trials mentioned in this episode include:ADAURA Trial IMPOWER010CHECKMATE816Q: We've previously discussed that adjuvant cisplatin doublet chemotherapy is used for tumors > 4cm and/or nodal involvement. Given that PD-L1 status and EGFR status can also potentially change adjuvant therapy choices, how do you employ these tests in your practice?* Different approaches at every center/with different thoracic oncologists. * Dr. West does NOT recommend sending broad NGS testing on everyone if it is not going to change management. * It it may influence management, at the very least, PDL1 and EGFR should be performed because of implications on adjuvant treatment options (See Episode 026 for treatment discussions): ** ADAURA Trial: Adjuvant Osimertinib x3 years for EGFR+ patients** IMPOWER010: In patients with PDL1 >50%, patients did better with 1 year of immunotherapy (atezolizumab) after adjuvant therapy* In patients with higher risk disease, can consider sending broad NGS, particularly looking for ALK and other mutations; remember that EGFR and ALK+ patients do NOT respond to immunotherapy well. This is important because we don't want to give someone side effects that they would not otherwise had (these patients are getting treatment adjuvantly AKA after their disease is already resected!)Q: What are limitations of the ADUARA Trial? * The ADUARA suggested disease-free survival advantage with use of osimertinib, but we don't know final overall survival data yet.*Limitations:** Three years of therapy** Very expensive drug** More data presented at ESMO 2022 on efficacy; Dr. West stated that there appears to be drop off in survival after stopping drug. Overall survival data not yet available * Just because patients can get osimertinib does NOT mean that they are not eligible for chemotherapy**Adjuvant chemotherapy for patients provides long-term benefit** JBR.10 Trial: Older trial, but showed that patients who got adjuvant treatment (in this case vinorelbine plus cisplatin) had prolonged disease-free and overall survival in early-stage non–small-cell lung cancer.** Follow up study suggested that EGFR+ patients trended towards longer survival Q: What are your thoughts on Checkmate 816 with the use of neoadjuvant nivolumab in addition to the platinum doublet? Do you think pathologic CR was an appropriate surrogate endpoint for the trial?* Complete path CR is a new end-point, but it does correlate with PFS. We cannot always for traditional endpoints, such as overall survival data, to mature because doing so may result in us withholding therapy that may be very beneficial. * Biggest benefit to neoadjuvant treatment is that more patients are able to get the full regimen. Many have complications after surgery and never are able to then get/benefit from chemotherapy. Supported by data from NATCH trial Q: What are your thoughts on induction chemoradiation vs. chemotherapy alone?* Dr. West prefers to not use radiation pre-operatively, with some exception (for instance, pancoast tumor) Tune in next week for part 2 of this discussion!About our guest:Dr. Jack West is an internationally-renowned Thoracic Oncologist. Associate Professor in the Department of Medical Oncology & Therapeutics Research at City of Hope Comprehensive Cancer Center. He is also the Clinical Executive Director of AccessHope. He completed his medical education at Harvard Medical School, and then trained at Brigham and Women's Hospital before heading to Fred Hutchinson at the University of Washington. Twitter: @JackWestMD References:https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02098-5/fulltext - IMPOWER 010 Trial https://www.nejm.org/doi/full/10.1056/NEJMoa2027071- ADAURA Trial https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4032958/ - NATCH Trial https://www.nejm.org/doi/pdf/10.1056/NEJMoa043623 - JBR.10 Trialhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033998/ - Follow up to JBR.10 Trial looking at influence of EGFR status on chemotherapy responsehttps://www.nejm.org/doi/10.1056/NEJMoa2202170 - CHECKMATE 816 https://www.thefellowoncall.com/tfocpodcast/episode-001disclaimer-wfhgf-ml3b6-9m66a-8rrc4-k8w87-x7xdd-wrzye-4xg8x-t73gt-cxc5s-nmg8f-cfyd6-hgs35-5pcwx-tf6dh-trggt-xzkt7-923gg-rpjzx-6s36p-hk27n-bbpgx-jymml-9lfam-76m4s - Episode 026https://www.thefellowoncall.com/tfocpodcast/episode-001disclaimer-wfhgf-ml3b6-9m66a-8rrc4-k8w87-x7xdd-wrzye-4xg8x-t73gt-cxc5s-nmg8f-cfyd6-hgs35-5pcwx-tf6dh-trggt-xzkt7-923gg-rpjzx-6s36p-hk27n-bbpgx-jymml-9lfam-76m4s-6xae9-ws6nt-ntn8g - Episode 029Please visit our website (TheFellowOnCall.com) for more information Twitter: @TheFellowOnCallInstagram: @TheFellowOnCallListen in on: Apple Podcast, Spotify, and Google PodcastLove what you hear? Tell a friend and leave a review on our podcast streaming platforms!

How do we think about treatment of lung cancer? Recap on staging (see Episode 025) * Pro-tip: Highly recommend that you “forget” about the actual staging and focus more on the individual T, N, and M status * Tumor size:**T1a

In this episode, Lynn Tonini interviews Marcie Dearth, the Vice President of Residential Programs of IMPOWER in Longwood, Florida. We focused on their transitional housing program called The Village, which was developed as an extension of their mental health and child wellbeing core services. We also discussed opportunities for improvement of the foster care system, including more collaboration among organizations that serve these young people.

Our guest this month is Shawn Power, Life Coach and Owner of IMPOWER. Shawn wants to know if you desire to connect and engage with the world around you by waking up every day with a strong sense of clarity, confidence, and courage. If you do, you'll get a lot out of his IMPOWER program. Join us for a powerful conversation: 

Are you ready to make 2022 the best year of your life? "Inspiring Experiences" outlines how to chart your course into life, love and making your dreams come true!

“Knowledge is power, but only when paired with action” In this episode we speak with Kay Farlow, Founder of the IMPower Center. IMPower Center is an organization on a mission to promote the financial literacy of youth and adults covering topics like credit, real estate, and investing to help close the racial equity gap through education. IMPower Center is located in South Bend, Indiana and will help support the surrounding community through a full financial freedom curriculum. Want to learn more, donate, or get engaged? Facebook: https://www.facebook.com/IMPowerSB

Dave and Evan host their first TalkingHeadz foursome. In this episode we meet with Davide Petramala and Laura Faughtenberry of Avaya OneCloud CPaaS.Avaya is best known for its powerful enterprise contact centers which can now do even more with OneCloud CPaaS. In this podcast we find out more about how/when Avaya got into the CPaaS business, and how customers are using it to customize even faster and better services. Avaya OneCloud CPaaS is an Avaya public cloud service that offers APIs and applications as a service that can be used to customize and personalize communications and collaboration. This global platform allows developers, partners and customers to build agile and burstable mobile and web applications via CPaaS building blocks. Case studies include Harris County and Nebraska Medicine as well as: CTIntegrations https://www.avaya.com/en/success-stories/ctintegrations/6 Points https://www.avaya.com/en/success-stories/6-points/IMPower https://www.avaya.com/en/success-stories/impower-solutions/

As part of the OncView video series, CancerNetwork spoke with Mark Socinski, MD, of the AdventHealth Cancer Institute in Orlando, Florida about updates in the management of extensive-stage small cell lung cancer (ES-SCLC). Socinski touched on a number of important aspects of treating this disease, including the existing standards of care, treatment challenges, immunotherapy, IMpower 133 trial, and more. Don't forget to subscribe to the "Oncology Peer Review On-The-Go" podcast wherever you get your podcasts.

Dr. Jason Luke, director of the Cancer Immunotherapeutics Center at UPMC Hillman Cancer Center, discusses advances in immunotherapy across the spectrum of malignancies featured at the 2021 ASCO Annual Meeting.   Transcript:  ASCO Daily News: Welcome to the ASCO Daily News podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. My guest today is Dr. Jason Luke, the director of the Cancer Immunotherapeutics Center at UPMC Hillman Cancer Center. Dr. Luke also serves as associate professor of medicine at the University of Pittsburgh School of Medicine. His clinical focus is on immunotherapy for advanced solid tumors, as well as cutaneous malignancies and melanoma. He joins me to discuss advances in immunotherapy featured at the 2021 ASCO Annual Meeting. Dr. Luke has relationships with most of the pharmaceutical companies that have funded the research discussed in this episode. His full disclosures are available on the transcript of this episode. Dr. Luke, always great to have you on the podcast. Dr. Jason Luke: Well, thanks so much for the invitation today. ASCO Daily News: Well, there was an abundance of novel therapies and practice-changing studies presented during this year's [ASCO] Annual Meeting. Did you detect any themes among all of the great studies presented during the meeting? Dr. Jason Luke: Well, I agree. And as I was sort of taking the fire-hose of abstracts in this year, I thought there were four themes that really seemed to stand out to me. And when I was thinking through them, I think the first one was the validation of a new checkpoint, or a third validated checkpoint for use in clinical practice. A second one was really the emergence of immunotherapy, now being used in the curative setting, meaning either in adjuvant studies or in neoadjuvant studies. And the third area was advancements in this management of metastatic disease with practice-changing trials. And then the fourth area, which is always near and dear to me, is novel therapeutics with the development of the next generation of immunotherapies, and those early data that might give us a hint towards what might be coming next. ASCO Daily News: OK, so let's first look at the third validated checkpoint for use in clinical practice. That's Abstract 9503. Dr. Jason Luke: Yeah, absolutely. So this year at ASCO, we saw the results of a clinical trial described as the RELATIVITY-047 study, which was a global randomized double blind phase II/III study comparing anti-PD-1 antibody with nivolumab (nivo) versus a combination of nivolumab with the anti-LAG-3 antibody relatlimab. And so LAG-3 is a molecule that many will be familiar with, but perhaps not everyone. And LAG-3 is another receptor on T cells that can become up-regulated as T cells become dysfunctional in the tumor microenvironment. And so all are aware of the concept that infiltrating lymphocytes can get into tumors, and then they get blocked by these immune checkpoints. And so LAG-3 is another immune checkpoint expressed on these tumor infiltrating lymphocytes. And I don't have time to go into all of this, but in the preclinical space, blocking LAG-3 with an antibody is actually, in many mouse models, more effective than blocking a PD-1 or PD-L1. And so there's been a lot of interest. LAG-3 was one of the first targets to really develop as a co-target to PD-1. And just to zoom forward then to the clinical trial, this was a study where patients with advanced, untreated, metastatic melanoma were randomized one to one to either get relatlimab plus nivolumab, in what they are describing as a fixed dose combination, meaning that there's an infusion of the dose once a month, relatlimab 160 milligrams plus nivolumab 480 milligrams. And that was the same dose. And so it's only one infusion, even though it's two drugs, one infusion. That was compared with nivolumab. And there were a number of stratification factors, et cetera, in the study. And they're useful to get into the minutia, but right now, I think not so important. This, like I said, was a gated study, meaning they did a phase II trial first, to try to prove that there was a benefit in a smaller sample of patients. And if they hit the endpoint, they then went on to a phase III trial. And that's exactly what happened. So in this trial, progression-free survival (PFS) was the primary endpoint. And, interestingly, it was evaluated by blinded independent central radiology. And that may sound like a mouthful, but we'll come back to why that's important a little bit later. And there was a hierarchical testing strategy, such that the PFS had to be established first, before the investigators can look at overall survival and overall response rate. But given that background, there really was a quite substantial and clinically impressive difference between these two arms. And so we call relatlimab "rela" for short. So rela plus nivo demonstrated a substantial improvement, markedly statistically significant improvement, compared with nivolumab monotherapy, so that at 1 year, at 12 months, the progression-free survival for the combination arm was 47.7%, compared to 36% for nivolumab. And the median PFS was 10.1 months for the combination versus 4.6 months from nivolumab. So you can see that's more than a doubling of progression-free survival, with a hazard ratio at 0.75 and a p value at 0.006 or 0.0055. So why does that matter? Well, we have thought for a long time in the field about combination immunotherapy, and people think of PD-1 and CTLA-4 combination. And these data, when compared sort of across trial comparison, which is always a little dangerous, but they look very similar to what we saw with nivolumab plus ipilimumab (ipi), in terms of the absolute improvement in the benefit in terms of median progression-free survival, between relatlimab plus nivo, as compared with ipi plus nivo in the CheckMate-067 study. And I mentioned this blinded independent central radiology, that complicates things a little bit, because the landmark comparisons between having the radiologist evaluate the scans and having the investigators evaluate the scans, actually gives a little bit of variation in terms of the outcomes. But if you just compare them on a high level, they actually look very similar. And along those lines, the really important thing is that relatlimab plus nivolumab is much better tolerated with much less side effects than nivolumab plus ipilimumab. So, in fact, in this clinical trial, we see that the rates of grade 3-4 adverse events are on the order of what we saw with nivolumab monotherapy in CheckMate-067. Now, interestingly, in this study, RELATIVITY-047, the rates of grade 3 adverse events for nivolumab monotherapy were actually about half of what they had been seen in the previous phase III trial. And I think that that just suggests that all of us, as a field, are getting better at managing these immune therapy toxicities. One other piece of information that was very interesting to look at was when the outcomes were broken down by subgroups, particularly the biomarkers of PD-L1 positivity, and LAG-3 positivity. These biomarkers actually did not inform the outcomes, in which case, I mean, that nivolumab plus relatlimab was actually effective across all the subgroups. And so one might have hypothesized, going into this, that patients with high LAG-3 would do better with a LAG-3 treatment. That was not what was seen. In fact, all patients benefited with the combination. And that's relevant to clinical practice, because, as we think about applying this treatment, I do not think we're going to be able to use biomarkers, at least initially, to be able to differentiate who should get what. And rather this just suggests that basically all patients who are going to get PD-1 monotherapy would be better served by giving the combination. So I was the discussant actually for this abstract, and one of the questions I tried to get at was, well, does that mean that you would just essentially replace PD-1 monotherapy across the board in melanoma with this combination? And I think the answer is, not quite yet, but maybe someday. And what I mean by that, is that there are still some very high-risk patients that we treat. And particularly those are patients with high lactate dehydrogenase, brain metastases, rapid progression, et cetera. And those are the patients where, at least I, predominantly use nivolumab plus ipilimumab, or nivo plus ipi. And that's because nivo plus ipi is the treatment for which we have the best long-term data, and we know the most about it in terms of treating high risk patients. So I would continue to use that until this trial, at least. Is more mature, so that we can get data about the response rate, the overall survival, and so on and so forth. But I think there's really no question, looking at this relatlimab plus nivolumab data, that it does change the standard of care in melanoma, and that, for most patients, who would have gotten PD-1 monotherapy, they're now going to be directed towards this combination, given it's well tolerated and appears to be highly active. And I think, thinking beyond melanoma now, if this is now a second, a third checkpoint, but a second one we can combine with nivolumab with little toxicity, I think it opens up a huge new world of clinical investigation, possibly adding doublet checkpoint to chemotherapy. Basically everyone everywhere we've seen PD-1 combined with chemotherapy, and obviously that's quite exciting just thinking about improving outcomes. And we're going to discuss all the different ways that PD-1's been impacting the standard of care across different settings. ASCO Daily News: Excellent. Well, let's shift our focus now to the curative use of immunotherapy. Let's start in the adjuvant setting with the KEYNOTE-564 study. That's LBA 5. Dr. Jason Luke: So plenary presentation for the KEYNOTE-564 study, which was adjuvant pembrolizumab versus placebo in high-risk renal clear cell renal cell carcinoma. And so this is an important trial, because there have been decades, actually, of immunotherapy clinical trials in the adjuvant setting, which have not demonstrated a benefit. That also includes actually VEGF-TKIs, which also did not show a benefit. But in this large study, so almost 1,000 patients, 994 patients, they were randomized one to one to receive pembrolizumab or placebo. And the eligibility population were pathological T2 with intermediate and high risk features all the way through metastatic disease that's been fully resected. And the outcomes here, again, I think were very impressive. And so the disease-free survival was statistically significant, with a hazard ratio of 0.68. And what does that mean in reality? Well, the 2 year disease-free survival was 77.3% for the patients getting pembrolizumab compared to 68.1% for those getting the placebo. So you can see basically a 10% 2 year improvement in disease-free survival. And though the data were quite immature, the early analysis of overall survival also suggested a statistically significant benefit. So p value was 0.02 and hazard ratio was 0.54. Now we'll be very interested to see how that matures over time. But I think again these are practice-changing data, to suggest that, basically, all high-risk patients with clear cell renal cell cancer are now going to be receiving anti-PD-1 immunotherapy in the adjuvant setting. I think it does raise the question, and we'll discuss it now across other diseases as well, in terms of, are we over-treating patients. But this has been a constant struggle in medical oncology for many, many years. But it's very hard to see a treatment like this, with such a benefit, and not think that you want to give this basically to almost all the patients. But, hopefully, biomarkers to inform which patients benefit most will be coming over the relatively near future for renal cell. But I think those are becoming a little bit more obvious in some other diseases. ASCO Daily News: Looking at non--small cell lung cancer, Abstract 8500, that's the IMPOWER-10 trial, that caught a lot of attention. That was trending on Twitter for a while. What are your thoughts on that trial? Dr. Jason Luke: Yeah, absolutely, so the IMPOWER-010 or 010 study, this study looked at PD-L1 inhibition in the adjuvant setting, versus a placebo. So this was another very large trial where patients with early to later high-risk disease, so stage 1b to 3a, they received standard chemotherapy as adjuvant treatment, but then were randomly assigned to get PD-L1 versus best supportive care. And this was an interesting clinical trial, [ and] had a complicated statistical design where the first analysis was to look at the impact in PD-L1 positive patients. Secondarily, then, they looked at randomized patients. And then thirdly, they looked at intention-to-treat. And this was a positive study. So in the disease-free, in the PD-L1 high patient population, the disease-free survival did not reach the median, with a 2 year benefit at 74.6% versus 61%, so again a 13% improvement in 2 year disease-free survival. And that was highly statistically significant, hazard at 0.66. And, again, that's the PD-L1 high population. So, thinking about biomarkers then, it looks clear that the PD-L1 positive group is the one that disproportionately benefits, because as we went through the rest of the hierarchical testing, the disease-free survival in randomly assigned patients, and then in intention-to-treat patients, those numbers got a little less strong. And it really probably suggests that the PD-L1 positive group is the one that's going to drive almost all of the benefit. So it'll be interesting to see how this data matures, and how it's interpreted in the community. I mean, you mentioned the discussions on Twitter, which I sometimes participate in. And I'm going to come back to a little later how it's very interesting to see how thought leaders for various malignancies sort of take these data into consideration. I think clearly in GU cancers, when we talked about the KEYNOTE-564 pembrolizumab data, the sense was, this is an immediate change in the standard of care. When we look at this data for non--small cell lung cancer, however, the sense I've gotten from some investigators is, this is early data. And they really do want to see that overall survival before that's really going to have high uptake. But we'll have to kind of see how that goes. Maybe selecting for PD-L1 in that population would make that difference, to really let you feel confident. But it'll be interesting again, like I said, as more time passes and as we see more data, and as other PD-1, PD-L1 agents come into this same space, if there's reproducible data that will help them feel more confident. ASCO Daily News: Right, well, another trial that attracted a lot of attention was CheckMate-577. That's Abstract 4003. Do you think this trial will move the needle in esophageal or esophagogastric junction (GEJ) cancers? Dr. Jason Luke: So I think this is a real important trial, because we've historically thought of certain tumor types as immunotherapy sensitive versus not sensitive, melanoma, lung cancer, et cetera. And gastrointestinal (GI) tumors predominantly have fallen into that latter group, where we think where there isn't as much of a benefit. Obviously there are approvals for esophageal and gastric cancers, but I think this study really shows how we can move the needle in terms of maybe curing more patients. So CheckMate-577 looked at adjuvant nivolumab. And these were stage II and stage III patients with esophageal or GEJ, and they got neoadjuvant chemoradiation treatment and then surgery, all of that being standard of care, but then went on to get a randomization 2 to 1 to either nivolumab or placebo. And again, as you mentioned, this is an important trial. The disease-free survival (DFS) was statistically and substantially improved for the patients getting nivolumab versus placebo, after that definitive therapy. So in the group receiving nivolumab, the median disease-free survival was 22.4 months, compared to only 11 months in the patients getting the placebo. That was a hazard of 0.69 and a p value at 0.003. And, again, thinking about biomarkers here, there was a broad population of patients treated. But when you look at the breakdown of who benefited the most, the patients benefiting in this trial were almost entirely those patients who had a PD-L1 composite signature at greater than 5,  combined positive score (CPS) greater than 5. And so it's really the case that the PD-L1 positive patients with esophageal cancer seemed to benefit the most. And so I don't know how you think this doesn't impact the standard of care. In the total population there was a doubling of DFS, and in the PD-L1 high it was actually almost a tripling. And so I think, immediately, at least for PD-L1 high patients, they should go on to get adjuvant PD-1 after definitive chemotherapy, radiotherapy (RT), then surgery. And I think this is really exciting, when we think about, this is disease, obviously, it's very, very difficult to treat. And outcomes in metastatic disease are not what we want. And this really suggests we may be able to really benefit a lot of patients moving forward. ASCO Daily News: Excellent. So what are your takeaways from Abstract 9500, the KEYNOTE-054 trial of adjuvant pembrolizumab for melanoma? Dr. Jason Luke: Yeah. Thanks, so in melanoma we've had immunotherapy with checkpoint blockade now for a decade. And adjuvant clinical trials have been ongoing for most of that decade. And it's been standard of care to give our patients checkpoint blockade again for several years. I think what was really interesting about the update for KEYNOTE-054, which was the study of pembrolizumab (pembro)  versus placebo in stage III melanoma, was the authors on this update looked at the impact of crossover after initial progression. So in the clinical trial, patients were randomized one to one to either receive pembro or placebo. And at the time of progression, they could then cross over and get the other treatment, right? So this trial was the first trial to be designed to be able to ask that question, immunotherapy now versus immunotherapy later. And what we observed in this study was that the response rate to getting pembrolizumab in the metastatic setting, if you had gotten the placebo on the adjuvant trial, was approximately similar. It was right around 40% And that's actually what we saw on the KEYNOTE-006 study that got pembrolizumab registered. So that was really, really interesting. And it suggested that if patients progress in the adjuvant setting and get treatment with PD-1 in the frontline metastatic, and they're still in good shape, they actually can have similar outcomes than what we would have expected if they had not had that adjuvant experience. And so I think this is really important. It doesn't actually answer the question about overall survival, which is really what we want to know. Does adjuvant immunotherapy improve overall survival? But it does suggest that patients can have this benefit, even if they wait for treatment. One thing that was really interesting to see was that, for those patients who had pembrolizumab, in the adjuvant setting, and then had a progression event, who went on to get pembrolizumab again, actually had much lower outcomes. And so I think that that's something to be cautious about. I think if patients progress on adjuvant PD-1, the data from this trial really suggest that going back to PD-1, even if there's been a period of time, is not a real great idea. And many of us in the field have kind of advocated of going to CTLA-4 combination in those patients anyway. But I would think these data really do suggest that that's important. So broadly speaking, then, I think these data are important to suggest that if you wait to give immunotherapy, you can still get a good benefit, at least in melanoma. And what I thought was really interesting across all of these abstracts, so for kidney cancer, lung cancer, esophageal, melanoma, was we saw, I think, based on the investigator feedback, or the thought leaders in the field, was that disease-free survival or relapse-free survival was really interpreted somewhat differently in different settings. And so I think, in melanoma, I think we have for a long time thought that adjuvant therapy was important, despite the fact, we don't have overall survival for PD-1 antibodies. In the renal cell data, again, where immunotherapy has been a backbone, albeit with IL-2 and various different immunotherapies, again, a lot of enthusiasm. When we looked at lung cancer and esophageal cancer, where I think investigators are more used to biomarker selection, they were a little more nitpicky about which populations we should treat. And so I'm very interested to see how this entire field sort of develops, and how the thought leaders for each disease take these data in. But, if you take a step back, on a really high level, when we think about giving PD-1 checkpoint blockade, it's generally speaking a low-toxicity treatment. And there's a tremendous impact on recurrence and potentially cure in the adjuvant setting. And that is just so exciting when we think about truly making a difference on cancer. We're talking about people never having recurrence and never dying of metastatic disease. And if we think about the outliers among the thousands of patients that have these diseases, and just go out to 5 years, 10 years from now, that's going to be a lot of people alive because they got immunotherapy after surgery. ASCO Daily News: Well, that would be fantastic. Thanks, Dr. Luke, for your great analysis of the adjuvant setting. Let's focus now on the neoadjuvant setting. Abstract 8503, the CheckMate-816 trial, seems to be on everyone's radar. What can you tell us about it? Dr. Jason Luke: Absolutely, so I think we just got done talking about adjuvant therapy. But an alternative would be to say, is there a way that we can deliver this immunotherapy, perhaps to enhance the immunotherapy and either improve the surgery or actually maybe even avoid the surgery, moving into the future. And so that is a really exciting paradigm as well. And so the first of these was in non--small cell lung cancer, the CheckMate-816 study. And the initial results of this study were actually presented at AACR earlier this year, but now updated here at ASCO. And what we saw was that there was a major improvement, 10 times improvement, in pathologic complete response for giving nivolumab plus chemotherapy. I mean literally 2% pathologic complete response with chemotherapy, up to more than 20% with this combination with immunotherapy. And what the investigators updated here was a number of details around the surgical plans, showing that the surgeries were easier, and the patients had better time recovering, due to lower disease burden for those that got the combination with immunotherapy. And I think that's really, really exciting, because, I mean, it suggests a paradigm in the future where we can reduce the amount of surgery. So one of the things was they looked at the number of open thoracotomies versus VATS procedures. And a number of patients who got immunotherapy had a much lower surgical burden. So, I think those data are really exciting. They're not quite ready for prime time yet, because I think we need larger studies to prove this, but I think the trend is, we'll talk through these different disease settings, really does suggest that immunotherapy is going to really change all of oncology, in terms of surgical paradigms, how we follow patients, et cetera. ASCO Daily News: Excellent. Dr. Luke, you spoke earlier about the phase III study of relatlimab and nivolumab. There's another study, Abstract 9502 in the neoadjuvant setting, right? Dr. Jason Luke: Yep, and so, in addition to the phase III data for relatlimab, there was also a neoadjuvant study from The University of Texas MD Anderson Cancer Center group, which I think was really, really useful in helping us feel more confident actually about the metastatic disease data, and about understanding where the field in melanoma is going. So, in melanoma, that's where, sort of taking a step back quickly to note that there have been a whole bunch of neoadjuvant clinical trials done over the last 3 to 4 years, and actually so many that we've already started to have meta-analyses to look and see and observe, I should say, that those patients actually who have major pathologic responses, and those with complete responses, generally speaking, don't recur. And this is really exciting. It's actually even led to clinical trial designs where we're actually deferring surgery in melanoma, where we give neoadjuvant therapy. We take out one node. And if it's a complete response (CR) we don't even do the surgery. So in the Abstract 9502, again relatlimab, the anti-LAG-3 antibody was combined with nivolumab. And I think what the important thing to highlight here was that the rates of pathologic complete response and major partial response actually looked very similar to what we saw with nivo plus ipi in previous clinical trials. So if you remember, the relatlimab data in the metastatic setting was only the PFS data, due to the statistical plan. But what we see here is that in the neoadjuvant setting, very similar outcomes for relatlimab plus nivo as what would have been expected for ipi plus nivo. And I think that gives us, again, more strength and more confidence that this is a very active combo, again, with lower toxicity relative to nivo plus ipi. ASCO Daily News: OK, well, Abstracts 4503 and Abstract 4504 looked at alternative management strategies in bladder cancer. Can you tell us about these data? Dr. Jason Luke: So these were two really interesting abstracts, I thought, from my perspective. And they really looked at management, alternative management strategies for muscle invasive bladder cancer. And so the first one, 4503, was the Hoosier Oncology GU study 16-257. And this was a study that looked at neoadjuvant nivolumab plus gemcitabine and cisplatin, with an evaluation for clinical outcome. So what I mean by that was, after the patients got this treatment, they were evaluated for whether or not they had had a clinical complete response, and then they were offered the opportunity to either not pursue cystectomy, which obviously is highly morbid, or to continue to be followed. And, very interesting, the study, for those patients who were deemed to have had a complete clinical response, 70% of them did not recur. And that's really exciting, because if you think about the population of patients with bladder cancer, many of them elderly, those cystectomies are highly morbid surgeries. And this suggests that we may be able to move into a future where we could give them upfront medical therapy and actually potentially avoid that surgery. The other abstract I thought was really interesting was sort of married to that, which was the 4504 abstract. And that was a clinical trial that looked at the neoadjuvant administration of pembrolizumab plus gemcitabine chemotherapy and radiation treatment. And, again, what they observed in that study was very high rates of pathologic complete response, and longer term outcomes that looked very exciting. And I think what both of these studies show, as phase II studies, is the possibility that medical therapy might actually be curative in some patients. And there are a number of phase III efforts now ongoing to try to amplify these trials and actually confirm them on a larger scale. ASCO Daily News: Shifting our focus now to practice-changing trials in metastatic disease, GI oncologists were very pleased to see the data from CheckMate-648. What was observed in this trial, LBA 4001? Dr. Jason Luke: So CheckMate-648 in esophageal cancer was a study in the frontline metastatic setting, looking at the impact of immunotherapy plus chemotherapy, or immunotherapy alone versus chemotherapy. And so what I mean by that was one arm in the study looked at nivolumab with standard chemotherapy, compared to chemotherapy, and the other arm looked at nivolumab plus ipilimumab versus chemotherapy. And, very briefly, what was observed was that both of the active arms, so the immunotherapy containing arms, the nivo plus chemotherapy or the nivo plus ipi, both of them improved outcomes compared with chemotherapy. And so, moving forward, there's really no question now that the standard of care in the frontline management of esophageal cancer should include immunotherapy, either as a combination with chemotherapy, or possibly with leaving out the chemotherapy and giving just nivolumab plus ipilimumab. Now the sub-stratification of patients and their outcomes by sub-stage was important in this study, and again emphasized that it's mostly the PD-L1 positive patients who benefited the most from immunotherapy. So but the idea of potentially having a regimen that's chemotherapy-free for frontline esophageal cancer, I think is really exciting. And I'd be really interested to follow where this field goes in terms of which patients are getting selected for the nivo chemotherapy versus ipi plus nivo arms, in standard practice kind of moving into the future. And obviously further biomarkers will be really important. But I think this is really a practice-changing trial, again, to emphasize that all patients with esophageal cancer should be getting immunotherapy in the frontline, moving forward. ASCO Daily News: Indeed, what can you tell us about Abstract 6000 using camrelizumab for nasopharyngeal carcinoma (NPC)? Dr. Jason Luke: Yeah, absolutely. So I think that this is a really interesting study and I think important. This is a study actually looking at the impact of adding immunotherapy to chemotherapy in nasopharyngeal carcinoma. So all the oncologists in the United States will be like NPC, oh, yeah, I heard about that during fellowship. But this is actually a major source of morbidity and mortality throughout the rest of the world, especially in the developing world. And so this clinical trial to me is very interesting. So the short story here is that adding camrelizumab improved outcomes relative to chemotherapy, which I think is probably not surprising, because across many other settings we've seen that adding PD-1 to chemotherapy would improve outcomes. I think the difference here was that this is an antibody that was developed in China. And is it part of a growing trend to see competitor PD-1 PD-L1 antibodies entering the space. So to close the loop on NPC, I think these data really strongly suggest that we should be giving immunotherapy in combination with chemotherapy in the frontline to these patients. But I think, more broadly, start to open this conversation about how are we going to evaluate new drugs that are getting developed, say, only in China, or in other parts of the world where there are no patients from the United States that are actually participating in the clinical trial. Are those drugs going to get approved by the U.S Food and Drug Administration (FDA)? And if they do get approved by the FDA, how are they going to get priced, because as we're moving into the era now of more than 10 anti-PD-1, PD-L1 antibodies that have shown a benefit in the metastatic setting in phase III trials, one could imagine the time has finally come for price control, and not control, but price competition. It'll be really interesting to see whether or not that actually comes true. I don't know the answer yet. But this trial, I think, is very important in that regard. ASCO Daily News: And back to melanoma, can you tell us about advances in the metastatic setting? Dr. Jason Luke: Absolutely. So I think there were two to hit on quickly. Obviously there were more, but two quickly to hit on. One was Abstract 9506, which was the long term update, 6 and a half years of CheckMate-067, which people remember was the nivolumab plus ipilimumab versus ipi trial. And just to summarize this quickly, it really was amazing to see that now at 6 and a half years, we finally hit the median for overall survival for patients with metastatic melanoma in the frontline setting. And the median was 49%. So it just barely went under the median. But I just can't emphasize, when I was a fellow, and actually I'm a melanoma oncologist, and coming into this, the outcomes for patients at that time, the median survival was 9 months. And now we're talking about 10 years later, and the median is basically, it's 6 and a half years, almost 50%. So it's just outstanding. And I can't emphasize it enough. Clearly not good enough. We still have 50% of patients who need better treatments. But it's pretty exciting. The other abstract I wanted to highlight, because I think it differentiates where things stand, was the Abstract 9505, which was the tumor infiltrating lymphocyte (TIL) lifileucil in melanoma. And, again, just to highlight this, 36.5% response rate to re-infusion of TIL with interleukin-2. And I think that that's going to be an important part of the armamentarium for melanoma management, moving into the future. One final metastatic disease abstract to highlight was the development of T cell receptor (TCR) T cells for synovial sarcoma. So this was a really important abstract as well, going along with the lifileucil abstract, because I think this showed that this is a really active regimen with adoptive cell transfer for synovial sarcoma. And I would very much expect to see that both the TCR T cells and the TIL product get approved by the FDA within the coming year. ASCO Daily News: Excellent, well, before we wrap up the podcast, can you share some highlights from your main research area, developmental therapeutics? Dr. Jason Luke: Yeah, finally, so in the realm of developmental therapeutics, which is my major research area, there's always a lot going on. And I think this year's ASCO Annual Meeting I would just highlight a few things. So one is the continued development of VEGFR2 tyrosine kinase inhibitors (TKIs) with immunotherapy, we saw long term updates with lenvatinib and pembrolizumab in melanoma (Abstract 9504). And we saw other updates with new combinations in colorectal cancer. Another area in terms of considerations were small molecule inhibitors. And so there was a really interesting abstract about an MDM2 inhibitor. And people will remember that's a regulator of P-53, being combined with pembrolizumab. And preclinically and translationally, in this abstract, it appears that modulating the P-53 pathway via MDM2 actually has immunomodulatory effects. So it'll be very interesting to see where alrizomadlin goes (Abstract 2506).  There are a number of other novel targets. And there's so many abstracts on these that I'm not going to really go through them in a lot of detail. But TLR-7/8 agonism with checkpoint blockade looks interesting (Abstract 2512). There were a number of abstracts around transforming growth factor, TGF beta. And this is a really important target in cancer. And it'll be interesting to see how that gets developed out further. There were a number of approaches looking at targeting of human papillomavirus or HPV, one of them, which was a triplet regimen of an HPV vaccine plus a cytokine plus a PD-L1 antibody, and another one which was some viral vectors expressing HPV proteins. So all of this, I think, very interesting and taking sort of orthogonal to checkpoint approaches in terms of immunotherapy, vaccines, cytokines, viral vectors, et cetera. And then the final area, just to highlight, there was one very interesting Abstract 2507, which was a novel CAR T-cell product, which included a 41BB activation domain, attached actually to a bispecific CAR that binds to both CD19 and CD20. And this was Abstract 2507, and what I thought was very interesting was the rates of response for this molecule are really high, almost 100%. And that even included patients who had previously progressed on other CAR T products. So not enough time to go and give justice to any of these, but there's so much going on in developmental therapy for immuno-oncology. And I think that just emphasizes how bright the future is, building on this tremendous benefit in the standard of care setting in the adjuvant and metastatic settings. So, very excited to see where all these molecules go, and hopefully to advance the outcomes for all of our patients. ASCO Daily News: Indeed. Dr. Luke, thank you, as always, for your fantastic insight on some tremendous advances in immunotherapy, across the spectrum of malignancies. Our listeners will find links to all of the studies that you discussed in the transcript of this episode. Thank you, Dr. Luke. Dr. Jason Luke: Well, thanks so much for the opportunity. ASCO Daily News: And thanks to our listeners for joining us today. If you enjoyed this episode of the podcast, please take a moment to rate and review us wherever you get your podcasts.   Disclosures: Dr. Jason Luke Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical, Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, and Arch Oncology Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, Immunocore, KSQ Therapeutics, Inzen, Pfizer, Silicon Therapeutics, TRex Bio Research Funding (Institution): Merck, Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Research Funding: Array BioPharma, Agios, Astellas Pharma, EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., Trishula Therapeutics, BioNTech AG, Scholar Rock Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof) Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

While the NHS rose to the challenge of the Covid crisis, the impact of the pandemic on the nation's health is now becoming clear, with millions missing out on hospital treatment, and thousands more suffering Covid-related health problems. Liam Sloan and Dr Mark Simpson are joined by James Swaffield from Impower, a consultancy working to improve public services in the UK, to discuss the post-Covid outlook for the NHS and public health including:   Immediate challenges faced by the NHS How the NHS is managing ‘burnout' among staff Tackling the pandemic backlog of ‘missing patients' Addressing patient health inequalities The role of employers in supporting workforce health post-pandemic Presented by Liam Sloan and Dr Mark Simpson. With James Swaffield. Produced by James Seton. Production and editing by Nick Hilton for Podot.

Rob Moyer is the Co-Founder and President of Agility Partners, LLC an IT recruiting and consulting company headquartered in Columbus. In this episode, we talk with Rob about his path to tech, building a new business, and taking risk for greater upside.  Founded in 2017 in his spare bedroom, Rob (and his partner Alan) self-funded AP and immediately began to disrupt the industry by building a greenfield, referral-based technology platform called Connect. In 2020, Agility Partners formally stood up its automation consulting division, Impower.ai.  Over those four years, AP has grown to 100+ employees in several states and has been recognized by the community and the industry for their innovation, diversity, and culture.Rob lives in Grandview Heights, is a member of the Information Systems Advisory Board at Ohio University where he graduated, and is intimately involved in the tech community in Columbus and beyond.  In his free time, Rob invests, travels, acts like he golfs, and enjoys a stiff, smoked Old Fashioned at No Soliciting.Connect with Rob on LinkedIn: https://www.linkedin.com/in/robmoyer/For more information on Agility Partners, please visit: https://agilitypartners.io/

Join me on this weeks episode as I talk with  Gary Doherty, Founder of Think Network, TedTalk speaker and author.Be prepared to get fired up as he digs into what it really looks like to live an empowered life and take empowerment everywhere you go. You can follow Gary on Instagram @garydohertyofficialCheck out www.thinknetwork.coMentions Find out more about The Colourful Biz SocietyhereFind out more about the IMPower community membershiphere

In this episode I invite Alice Cherno, a member of the IMPower community for a coaching session about her work, her developing artistry and building boundaries on her growing journey.This is a real life coaching session. Listen in and enjoy. Find out more about The Colourful Biz Society here Find out more about our community membership here 

Rachel Zhou and Angelina Del Favero were just 14 when they started publishing imPower magazine. The first two editions – focusing on family harm and modern slavery – were sent to every secondary school in the country. Now 17, they're working on a third all about body image. See acast.com/privacy for privacy and opt-out information.

Interviewed J-Black coach from Brighton High School. We talked on Sports & Politics & Marginalized Athletes. J-Black message is to Impower our youth for tomorrow. --- Support this podcast: https://anchor.fm/6seventeenpodcast/support

“I want to empower women through education, leadership development, and community engagement”   In episode 5, Lori sits down with Produce Industry Legend, Margaret D'Arrigo-Martin. Margaret has been an advocate, inspiration, and example for women her entire career. She has made a positive difference in the community, the nonprofit sector, and the agriculture industry, both locally and globally.   “What you're putting in your body makes a huge impact on your ability to think, function, and feel your best”   Margaret spent 22 years as executive vice president of sales and marketing at D'Arrigo Bros. She has more recently spent the last several years as vice president of community development at Taylor Farms. She served as Director of the industry's leading trade organization-- Produce Marketing Association. She was named Woman of the Year by Ag Against Hunger. Her leadership in the non-profit sector includes President of the Grower Shipper Association Foundation, Vice President for Hartnell College Foundation and president of the Salinas City Elementary Educational Foundation.   “My journey didn't come easy. I had to push and climb, but I never gave up”   Margaret serves on the board of directors Children's Council of Monterey County, Literacy Campaign for Monterey County, Thrive Foundation, Salinas City Center Improvement District,  and Steinbeck Innovation Foundation. She is co-founder of IMPOWER, a primarilyy woman-focused group whose purpose is to get others involved in making our community a better place. She also currently serves as Secretary of Salinas Valley Memorial Health Care System.   These accomplishments are testimony to the passion Margaret feels for her community and industry. She has a vision for what is possible and has proven that it is also achievable.   Some Topics we talk about in this episode:   Introduction // Margaret D'Arrigo-Martin - 0:45 Margaret's Background and Experience in Produce - 2:45 How Fresh Produce Can Help You Reach Your Full Potential - 7:30 Margaret's Role in the Produce Industry - 9:43 The Importance of Having Mentors - 14:01 What is the One Thing Moms need to know about Fresh Produce - 18:35 Advice from Margaret - 19:20 Wrap-up - 21:40   For more information about Margaret D'Arrigo-Martin and the work she is doing to empower women and make waves in the produce industry, visit https://www.margaret-inc.com/ and https://www.impowerwomen.org/ to connect with her and her team.   How to get involved   Join The Produce Moms Group on Facebook and continue the discussion every week! https://www.facebook.com/groups/316715662104709/ Reach out to us - we'd love to hear more about where you're at in life and business! Find out more at www.theproducemom.com   If you liked this episode, be sure to subscribe and leave a quick review on iTunes. It would mean the world to hear your feedback and we'd love for you to help us spread the word!

We have have returning guest Kevin Ramirez head coach at Impower. We talk about his new amino supplement. Kevin is a vision and neuro coach. Check out his web site www.impower.ca

Today we have Kevin Ramirez head coach at Impower. Kevin uses the latest neuroscience and sports vision to optimize performance. You can find him at www.impower.ca.