Podcasts about Abstract

In this episode of Behind the Knife, Dr. Patrick Georgoff sits down with Dr. Keri Seymour and Dr. Joey Lew to tackle the complex world of gastrostomy tubes. What may seem like a routine and straightforward procedure is anything but—full of nuanced patient considerations, timing dilemmas, technical challenges, and potential complications that can turn a “simple” consult into a 2 a.m. call you won't forget. From who truly needs a G tube and when to managing difficult post-op issues like dislodgement and buried bumper syndrome, this episode breaks down the practical, evidence-based approach every surgeon should know. Whether you're managing stroke patients, trauma cases, or navigating the tricky administrative obstacles around enteral access, this episode will equip you with the insights and strategies to confidently dominate your G tube consults. Hosts:  ·      Dr. Patrick Georgoff (Acute Care Surgeon, Duke University) ·      Dr. Keri Seymour (Minimally Invasive & Acute Care Surgeon, Duke Regional) ·      Dr. Joey Lew (Surgical Resident, BTK MIS Team) Learning Goals: By the end of this episode, listeners will be able to:  ·      Understand the nuanced indications for gastrostomy tube (G tube) placement. ·      Learn which patients truly benefit from G tubes, and when enteral access is not appropriate or indicated. ·      Appreciate the importance of goals of care discussions, assessment of comorbidities, and decision-makers—especially in neurocritical and elderly populations. ·      Know evidence-based timing for gastrostomy tube placement in stroke, TBI, and other complex scenarios. ·      Understand guideline recommendations and the clinical reasoning behind trial periods of nasogastric feeding versus early G tube placement. ·      Describe technical approaches to G tube placement and how to tailor the method to patient anatomy and clinical context. ·      Solidify knowledge of when to choose endoscopic, laparoscopic, open, or interventional radiology-guided placement. ·      Recognize, manage, and strive to prevent common and serious complications of G tubes, including early and late dislodgement, buried bumper syndrome, infection, bleeding, and gastrocutaneous fistula. ·      Discuss perioperative considerations, including anticoagulation, patient stability, and post-procedural care. ·      Understand why routine suturing of the G tube or bumper is not recommended, and how administrative and facility factors can drive clinical decisions. ·      Gain practical pearls and quick decision trees to dominate G tube consults and troubleshooting, day or night. References: ·      Braun R, Han K, Arata J, Gourab K, Hearn J, Gonzalez-Fernandez M. Establishing a clinical care pathway to expedite rehabilitation transitions for stroke patients with dysphagia and enteral feeding needs. Am J Phys Med Rehabil. 2024;103(5):390-394. doi:10.1097/PHM.0000000000002387 https://pubmed.ncbi.nlm.nih.gov/36867953/ ·      Burgermaster M, Slattery E, Islam N, Ippolito PR, Seres DS. Regional comparison of enteral nutrition-related admission policies in skilled nursing facilities. Nutr Clin Pract. 2016;31(3):342-348. doi:10.1177/0884533616629636 https://pubmed.ncbi.nlm.nih.gov/26993318/ ·      Chaudhry R, Kukreja N, Tse A, Pednekar G, Mouchli A, Young L, Didyuk O, Wegner RC, Grewal N, Williams GW. Trends and outcomes of early versus late percutaneous endoscopic gastrostomy placement in patients with traumatic brain injury: Nationwide population-based study. J Neurosurg Anesthesiol. 2018;30(3):251-257. doi:10.1097/ANA.0000000000000434 https://pubmed.ncbi.nlm.nih.gov/28459729/ ·      Cleverdon SA, Costantini TW, McGrew TM, Santorelli JE, Berndtson AE, Haines LN. Dysphagia in patients with traumatic brain injury, how often do they really need feeding access? Presented at: Academic Surgical Congress; February 2025; Washington, DC. Abstract 92.33. ·      Cmorej P, Mayuiers M, Sugawa C. Management of early PEG tube dislodgement: simultaneous endoscopic closure of gastric wall defect and PEG replacement. BMJ Case Rep. 2019;12(9):e230728. doi:10.1136/bcr-2019-230728 https://pubmed.ncbi.nlm.nih.gov/31488448/ ·      Galovic M, Stauber AJ, Leisi N, et al. Development and validation of a prognostic model of swallowing recovery and enteral tube feeding after ischemic stroke. JAMA Neurol. 2019;76(5):561-570. doi:10.1001/jamaneurol.2018.4858 https://pubmed.ncbi.nlm.nih.gov/30742198/ ·      Gallo RJ, Wang JE, Madill ES. Things we do for no reason™. J Hosp Med. 2024;19(8):728-730. doi:10.1002/jhm.13263 https://pubmed.ncbi.nlm.nih.gov/38180160/ ·      George BP, Hwang DY, Albert GP, Kelly AG, Holloway RG. Timing of percutaneous endoscopic gastrostomy for acute ischemic stroke. Stroke. 2017;48(2):420-427. doi:10.1161/STROKEAHA.116.015119 https://pubmed.ncbi.nlm.nih.gov/27965430/ ·      Goldberg LS, Altman KW. The role of gastrostomy tube placement in advanced dementia with dysphagia: a critical review. Clin Interv Aging. 2014;9:1733-1739. doi:10.2147/CIA.S53153 https://pubmed.ncbi.nlm.nih.gov/25342891/ ·      Hartford A, Li W, Qureshi D, et al. Use of feeding tubes among hospitalized older adults with dementia. JAMA Netw Open. 2025;8(2):e2460780. doi:10.1001/jamanetworkopen.2024.60780 https://pubmed.ncbi.nlm.nih.gov/39976967/ ·      Hochu G, Soule S, Lenart E, Howley IW, Filiberto D, Byerly S. Synchronous tracheostomy and gastrostomy placement results in shorter length of stay in traumatic brain injury patients. Am J Surg. 2024;227:153-156. doi:10.1016/j.amjsurg.2023.10.012 https://pubmed.ncbi.nlm.nih.gov/37852846/ ·      Kobzeva-Herzog AJ, Nofal MR, Bodde J, et al. Implementation of a quality improvement initiative reduced adult inpatient gastrostomy tube dislodgements. Am J Surg. 2025;(article 116522). doi:10.1016/j.amjsurg.2025.116522 https://pubmed.ncbi.nlm.nih.gov/40782502/ ·      Kurt Boeykens, Ivo Duysburgh. Prevention and management of major complications in percutaneous endoscopic gastrostomy. BMJ Open Gastroenterol. 2021;8:e000628. https://pubmed.ncbi.nlm.nih.gov/33947711/ ·      Murphy LM, Lipman TO. Percutaneous endoscopic gastrostomy does not prolong survival in patients with dementia. Arch Intern Med. 2003;163(11):1351-1353. doi:10.1001/archinte.163.11.1351 https://pubmed.ncbi.nlm.nih.gov/12796072/ ·      Papavramidis TS, Mantzoukis K, Michalopoulos N. Confronting gastrocutaneous fistulas. Ann Gastroenterol. 2011;24(1):16-19. https://pubmed.ncbi.nlm.nih.gov/24714282/ ·      Rajan A, Wangrattanapranee P, Kessler J, Kidambi TD, Tabibian JH. Gastrostomy tubes: fundamentals, periprocedural considerations, and best practices. World J Gastrointest Surg. 2022;14(4):286-303. doi:10.4240/wjgs.v14.i4.286 https://pubmed.ncbi.nlm.nih.gov/35664365/ ·      Reddy KM, Lee P, Gor PJ, Cheesman A, Al-Hammadi N, Westrich DJ, Taylor J. Timing of percutaneous endoscopic gastrostomy tube placement in post-stroke patients does not impact mortality, complications, or outcomes. World J Gastrointest Pharmacol Ther. 2022;13(5):77-87. doi:10.4292/wjgpt.v13.i5.77 https://pubmed.ncbi.nlm.nih.gov/36157266/ ·      Singh D, Laya AS, Vaidya OU, Ahmed SA, Bonham AJ, Clarkston WK. Risk of bleeding after percutaneous endoscopic gastrostomy (PEG). Dig Dis Sci. 2012;57(4):973-980. doi:10.1007/s10620-011-1965-7 https://pubmed.ncbi.nlm.nih.gov/22138961/ ·      Thosani N, Rashtak S, Kannadath BS, et al. Bleeding risk and mortality associated with uninterrupted antithrombotic therapy during percutaneous endoscopic gastrostomy tube placement. Am J Gastroenterol. 2021;116(9):1868-1875. doi:10.14309/ajg.0000000000001348 https://pubmed.ncbi.nlm.nih.gov/34158462/ ·      Ward EC, Green K, Morton AL. Patterns and predictors of swallowing resolution following adult traumatic brain injury. J Head Trauma Rehabil. 2007;22(3):184-191. doi:10.1097/01.HTR.0000271119.96780.f5 https://pubmed.ncbi.nlm.nih.gov/17510594/ ·      Wick B. Timing of PEG tube placement in stroke patients with dysphagia: a multi-center retrospective cohort analysis using the TriNetX database. Am J Gastroenterol. 2024;119(10 Suppl):S1146-S1147. doi:10.14309/01.ajg.0001035684.98119.d5 Please visit https://behindtheknife.org to access other high-yield surgical education podcasts, videos and more.   If you liked this episode, check out our recent episodes here: https://behindtheknife.org/listen BTK Fan Favorites:  General Surgery Oral Board Review Course: https://behindtheknife.org/premium/general-surgery-oral-board-review Trauma Surgery Video Atlas: https://behindtheknife.org/premium/trauma-surgery-video-atlas Dominate Surgery: A High-Yield Guide to Your Surgery Clerkship: https://behindtheknife.org/premium/dominate-surgery-a-high-yield-guide-to-your-surgery-clerkship Download our App: Apple App Store: https://apps.apple.com/us/app/behind-the-knife/id1672420049 Android/Google Play: https://play.google.com/store/apps/details?id=com.btk.app&hl=en_US

Background Music for Sleep, Meditation, Relaxation, Massage, Yoga, Studying and Therapy - Deep Energy 2132 -2134 - Angels in the Abstract - Parts 1 - 3 AD FREE VERSIONS OF ALL THE PODCASTS ARE HERE: www.jimbutler.bandcamp.com …… Please remember to turn on automatic downloads, like and subscribe, tell a friend, share with your family and leave a review. All of those things help build the podcast. Thank you so much!! ………. This podcast is ad supported. We try the best we can to keep all of the ads at the front and the back of the podcast, but depending on the length of the podcast, there maybe ads in the middle. Please check my Bandcamp page for ad free podcasts. www.jimbutler.bandcamp.com ……………………….. Watch me play live on TikTok @jimbutlermusic or On the Insight Timer App as Jim Butler Links for all of the podcasts in the Deep Energy Podcast Network: Deep Energy Podcast (Current Episodes) https://podcasts.apple.com/us/podcast/deep-energy-podcast-music-for-sleep-meditation-yoga/id511265415 https://open.spotify.com/show/1DhN56DzDKc0FhQqR23v9c Deep Energy Classics - All of the ORIGINAL Episodes  https://podcasts.apple.com/us/podcast/deep-energy-classics-original-episodes/id1734274408 https://www.spreaker.com/podcast/deep-energy-classics-original-episodes--6108618 https://open.spotify.com/show/7BjEFnqcyKWUkHcYdtFS25?si=05aeab39b5bc4a00 Deep Energy Daily Affirmations - Daily Affirmations to get you through the day https://podcasts.apple.com/us/podcast/deep-energy-daily-affirmations/id1729162791 https://open.spotify.com/show/0oaA8dRsWDQLkqeXmykGvu?si=461c7b47417b4e55 Deep Energy Guided Meditations - Guided Meditations to help through your day https://podcasts.apple.com/us/podcast/deep-energy-guided-meditations-with-michelle-davis-jim/id1732674561 https://open.spotify.com/show/1Kg2LTaFux10Ul94phybp8?si=ebbbf33757d64c13 https://www.spreaker.com/podcast/deep-energy-guided-meditations-with-michelle-davis-jim-butler--6098026 Slow Piano for Sleep - Solo Piano Pieces https://podcasts.apple.com/us/podcast/slow-piano-for-sleep-music-for-sleep-meditation-and/id1626828397 https://www.spreaker.com/podcast/slow-piano-for-sleep-music-for-sleep-meditation-and-relaxation--5572963 ………… www,jimbutlermusic.com jimbutlermusic@gmail.com All Social Media (FB - IG - YT - TT) is: @jimbutlermusic Merch: www.deepenergy.threadless.com Bandcamp Monthly No Ads Subscription/Patreon: www.jimbutler.bandcamp.com Custom Made Music: jimbutlermusic@gmail.com ………………….. Thank you for listening. All music is created, performed and composed by Jim Butler. AI IS NEVER USED TO CREATE MY MUSIC. Until the next time, please be kind to one another, peace, bye… …….. Original Image by the Dream App (not sponsored) or Canva (not sponsored) …………………. Become a supporter of this podcast: https://www.spreaker.com/podcast/deep-energy-podcast-music-for-sleep-meditation-yoga-background-music-and-studying--4262945/support.

Dark ObsessionPrepare yourself for a whirlwind journey through the highs and lows of life in Dark Obsession. India Ward seems to have it all by society's standards, but her personal life is unraveling beneath the surface. When faced with the realization that she merely exists rather than truly living, India must confront the pivotal choices that could alter her destiny forever.This compelling novella delves into themes of love, self-discovery, and resilience. As India navigates her tumultuous world, she encounters Mykell Hope—a suave, intelligent man who understands the game of life and its intricate rules. Together, they explore the delicate balance between heart and mind, teaching us profound lessons about life and love along the way.Dark Obsession is more than a story; it's a reflection on the complexities of the human experience, urging readers to embrace the transformative power of choice and authenticity. Dive in and discover what it truly means to live. Hosted on Acast. See acast.com/privacy for more information.

Can estranged family relationships actually be repaired? Drawing from research on reconciliation, Whitney outlines the five core ingredients necessary for genuine repair - active empathetic listening, accountability, behavioral change, mutual willingness, and safety. Whitney distinguishes between genuine repair efforts and surface-level compliance, explains when relationships are likely unsalvageable, and provides practical guidance for assessing whether reconciliation is truly possible or if it's time to accept the relationship's limitations. Whitney Goodman is a Licensed Marriage and Family Therapist (LMFT) and the founder of Calling Home, a membership community that helps people navigate complex family dynamics and break harmful cycles. Join the Family Cyclebreakers Club⁠⁠ Follow Whitney on Instagram | sitwithwhit Follow Whitney on YouTube | @whitneygoodmanlmft ⁠⁠Order Whitney's book, Toxic Positivity⁠⁠ This podcast is for informational purposes only and is not a substitute for professional mental health advice. 03:42 The Five Core Ingredients of Family Repair 13:09 When Relationships Are Unsalvageable 23:05 Genuine Repair vs Surface-Level Compliance 28:33 Assessing Capacity for Change https://callinghome.co/topics/family-estrangement/how-to-begin-reconciliation-with-an-estranged-family-member https://callinghome.co/topics/family-estrangement/should-we-be-estranged-checklist  https://callinghome.co/topics/accepting-your-parents/i-m-estranged-from-my-dying-parent-should-i-reconnect-and-help-them  [1] Kelley, D. L., Waldron, V. R., & Kloeber, D. N. (2019). A Communicative Approach to Conflict, Forgiveness, and Reconciliation. Routledge. https://www.routledge.com/A-Communicative-Approach-to-Conflict-Forgiveness-and-Reconciliation-Reimagining-Our-Relationships/Kelley-Waldron-Kloeber/p/book/9781138052666?srsltid=AfmBOoq4iGgtwMAvbAv4-FKP9EOORNLadpnlRmmGIY_rXYPEvirm7Ymr  [2] Tomm, K. (2002). Enabling Forgiveness and Reconciliation in Family Therapy. The International Journal of Narrative Therapy and Community Work. https://dulwichcentre.com.au/wp-content/uploads/2016/12/13-KarlT2.pdf  [3] Blood, P. (2012). The Repair and Restoration of Relationships. In Springer eBook (pp. 349-370). https://link.springer.com/chapter/10.1007/978-94-007-2147-0_17  [4] vanOyen Witvliet, C., Root Luna, L. M., Worthington, E. L., & Tsang, J. (2020). Apology and Restitution: The Psychophysiology of Forgiveness After Accountable Relational Repair Responses. Frontiers in Psychology, 11. https://journals.sagepub.com/doi/abs/10.1177/0091647120915181#:~:text=Abstract,promoting%20their%20empathy%20and%20forgiveness.  [5] Fishbane, M. D. (2019). Healing Intergenerational Wounds: An Integrative Relational–Neurobiological Approach. Family Process, 59(3), 1043-1063. https://pubmed.ncbi.nlm.nih.gov/31518458/  [6] De Mol, J., Lemmens, G., Verhofstadt, L., & Kuczynski, L. (2013). Intergenerational transmission in a bidirectional context. Psychologica Belgica, 53(3), 7–23. https://doi.org/10.5334/pb-53-3-7  [8] Byng-Hall, J. (2008). The significance of children fulfilling parental roles: implications for family therapy. Journal of Family Therapy, 30(2), 147-162. https://doi.org/10.1111/j.1467-6427.2008.00423.x[9] Paleari, F. G., Tagliabue, S., & Lanz, M. (2011). Empathic Perspective Taking in Family Relationships: A Social Relations Analysis. https://www.researchgate.net/publication/236587449_Empathic_Perspective_Taking_in_Family_Relationships_A_Social_Relations_Analysis Learn more about your ad choices. Visit podcastchoices.com/adchoices

What if Flight MH370 wasn't just lost, but simply became hidden from view? In this episode with controversial youtuber Ashton Forbes, we take the mystery seriously: not as magic, but as a challenge to what we think we know about plasma, quantum mechanics, and fusion. The question isn't about belief, but about possibility: if teleportation happened, what physical mechanisms could explain it? We're at the edge of reason for this one, where mystery bashes up again rationality.PATREON https://www.patreon.com/c/demystifysciPARADIGM DRIFThttps://demystifysci.com/paradigm-drift-showOUR HOMEBREWED MUSICCheck out our band's new album:https://secretaryofnature.bandcamp.com/album/everything-is-so-good-hereVinyl pre-orders available now: https://buy.stripe.com/14A5kC3Od5d21Ms7zPdEs09Ashton's YT Channel: https://www.youtube.com/@UCHmFQzkpaJBSDD1PPFhPPSg 00:00 Go! Introduction to Mysteries and Theories 00:06:09 Shadowy Experiences with NASA and LENR 00:10:53 Exploring Alternative Models for Energy Production 00:15:12 Secrecy and the Potential of Fusion Technologies 00:19:04 Enthusiasm and Skepticism in Energy Research 00:19:33 Fusion Funding and Accountability 00:23:02 Hypothetical Fusion and UFOs 00:29:07 Teleportation Theories and Their Implications 00:34:00 Espionage and Disappearance of Flight MH370 00:37:41 MH370 Emergency Communication and Eyewitness Accounts 00:40:00 Analysis of the Standard Narrative and Government Response 00:44:00 Military Tracking and Discrepancies in Reports 00:48:00 Satellite Evidence and Pinging Issues 00:52:00 Theories of Time Manipulation and Disappearance 00:54:00 Controversy Over Diego Garcia and Missing Evidence 00:56:00 Examination of Internet Misinformation 01:01:00 Impact of War and Accountability 01:05:00 Perception of Reality and The Nature of Truth 01:09:00 Gatekeeping Technological Advances 01:17:00 Aspirations in Technology and Public Perception 01:20:00 Public Distrust and Technology Disclosure 01:24:00 Alien Technology and Interstellar Travel 01:27:00 Theoretical Physics and Mediums of Travel 01:30:00 Teleportation and Energy Conversion Theories 01:32:07 Medium of Travel and Ether Concept 01:34:51 The Nature of Invisibility and Coupling 01:39:12 Theoretical Concepts of Wormholes and Energy Requirements 01:41:28 Material vs. Abstract in Physics 01:46:05 Validity of Advanced Technologies and Science 01:48:45 Understanding Electricity's Nature 01:50:51 Energy and Motion in Physics 01:52:41 Magic vs. Physics 01:54:58 Perception and Quantum Reality 01:58:01 Connectivity and Spacetime 02:01:30 The Role of Medium and Interpretation 02:05:54 Future of Rational Inquiry 02:09:15 Understanding Substructure in Physics 02:12:31 The Search for Ether 02:14:49 Advancements in Fusion Technology 02:18:18 Free Energy Challenges and Insights 02:20:38 Government and Scientific Disinformation 02:25:01 The Intersection of Physics and Secrecy 02:27:06 Disclosure and New Technologies 02:30:06 Innovations in Free Energy Technologies 02:35:01 Merging Physics and Spirituality 02:40:06 Open Dialogue and Friendship #quantumphysics, #quantummechanics , #Astrophysics, #TheoreticalPhysics, #PlasmaPhysics, #Teleportation, #AviationMystery, #FlightMH370, #PhysicsExplained, #NewPhysics, #fusion , #PhysicsCommunity, #BigQuestions #philosophypodcast , #sciencepodcast, #longformpodcast

Jon Jordan and Jenny Jordan talk through the week's news including:[0:35] Proof of Play is shutting down fully onchain game Pirate Nation.[3:08] As well as combat, it had a deep crafting system but never attracted enough players. [4:00] Its play-to-airdrop seasons artificially boosted audience but not revenues. [6:06] The main reason it shut was it cost $150,000 a month to run the underlying blockchains.[7:45] The PVE mode from the game is now available to play on the Abstract blockchain. [8:40] NFT holders will get a final airdrop of PIRATE tokens.[9:00] Proof of Play will continue to operate, focusing on "profitable business operations".[14:30] Ronin strategy game Wild Forest is rebooting, including a new PVE campaign. [18:45] The WF token is up 400% but still down 80% from its original launch.[21:26] South Korean game item marketplace Overtake has raised $7 million.[24:52] It's a web3 project based on existing web2 markets ItemBay and ItemMania. [25:33] Splinterlands has launched its cheeky $500,000 Crypto Game Recovery Fund.[27:35] It's giving assets to holders of NFTs from games which have shut down. [32:53] TGC Project O has been announced for Immutable.

Pudgy Penguins, the NFT project that once dominated the early 2021 NFT scene, has undergone a significant transformation, evolving from a digital collectible into a multifaceted ecosystem with physical products, social media influence, and a new digital token. ~This episode is sponsored by Tangem~Tangem ➜ https://bit.ly/TangemPBNUse Code: "PBN" for Additional Discounts!Guest: Luca Netz - Founder of Pudgy PenguinsPudgy Penguins Website➜ https://bit.ly/PudgyPBN00:00 intro00:07 Sponsor: Tangem00:40 Pudgy Surpasses Disney01:08 Abstract Chain Growth01:30 Could $PENGU flip $DOGE?05:20 Kanye Launches $YZY Token08:46 What if Labubu Launched a Token?11:32 Abstract on Phantom Wallet11:54 Phantom Stablecoin Coming?12:31 MetaMask Stablecoin12:49 Coinbase is an Offramp Now14:19 Polymarket, Pump.Fun, & Courtyard16:25 Death.Fun17:41 HyperFinance Gaming Potential19:39 Xbox Ally is An Open Platform21:07 Abstract Handheld Gaming21:40 XReal AR glasses22:41 AR is Now23:04 Meme Coin Shopping on Abstract24:42 $PENGU & $BONK Are The Top New Meme Coins27:56 Live Streaming on Abstract28:32 outro#Crypto #~Could $PENGU Actually Flip $DOGE?

✨ **Grab my Creative Direction template for FREE** ✨Curious what the first stage of my brand design projects looks like? Grab the Figma template (and four bonus audio trainings walking you through how to populate it!) below! I'll send it out September 1, 2025 (or automatically after that date) - are you ready?

Featuring an interview with Dr Jacob Sands, including the following topics: TROPION-Lung05 Trial: Datopotamab Deruxtecan for Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) with Actionable Genomic Alterations (0:00) Sands J et al. Datopotamab deruxtecan in advanced or metastatic non-small cell lung cancer with actionable genomic alterations: Results from the phase II TROPION-Lung05 study. J Clin Oncol 2025;43(10):1254-65. Abstract Phase III Randomized Clinical Trial Data with TROP2-Targeting Antibody-Drug Conjugates for Previously Treated Advanced NSCLC (6:52) Ahn M-J et al. Datopotamab deruxtecan versus docetaxel for previously treated advanced or metastatic non-small cell lung cancer: The randomized, open-label phase III TROPION-Lung01 study. J Clin Oncol 2025;43(3):260-72. Abstract Reinmuth N et al. Longer follow-up for survival and safety from the EVOKE-01 trial of sacituzumab govitecan (SG) vs docetaxel in patients (pts) with metastatic non-small cell lung cancer (mNSCLC). ASCO 2025;Abstract 8599. Paz-Ares LG et al. Sacituzumab govitecan (SG) vs docetaxel (doc) in patients (pts) with metastatic non-small cell lung cancer (mNSCLC) previously treated with platinum (PT)-based chemotherapy (chemo) and PD(L)-1 inhibitors (IO): Primary results from the phase 3 EVOKE-01 study. ASCO 2024;Abstract LBA8500. Evaluating TROP2 Expression Levels Through Normalized Membrane Ratio of TROP2 in the TROPION-Lung01 Trial (12:26) Garassino MC et al. Normalized membrane ratio of TROP2 by quantitative continuous scoring is predictive of clinical outcomes in TROPION-Lung01. WCLC 2024;Abstract PL02.11. CME information and select publications

On today's show, Episode 182, this is PART 1 of a Hebrew Scripture discussion that I had with Jeff Benner, who has authored over twenty books related to biblical studies. His works include The Ancient Hebrew Lexicon of the Bible and His Name is One. Jeff Benner founded the Ancient Hebrew Research Center in 1999. The stated objective is to help serious Bible readers break free from a surface-level understanding of scripture and to begin reading the Bible through the lens of its original language, culture, and context. Join me now for my discussion with Jeff Benner as we explore the rich nuances of the biblical texts. On today's program, we will study the Hebrew language from the perspective of its two-letter (parental) Hebrew root system. We will study words like Shalom, Faith, King, Abstract versus Concrete Thought, Righteousness, and many more concepts.  

On this episode, Paige chats with Jennifer Mullin - aka the “Occasional Creative”. Jennifer is a Madison, Wisconsin based mixed media artist, author, and art instructor whose whose love affair with the ballpoint pen has inspired artists all over the world.Jennifer shares how her creative practice shifted when limited time and space pushed her toward a sketchbook and a simple pen - an approachable medium she could explore anywhere, even from her couch. In 2016, her abstract ballpoint drawings went viral on Pinterest, leading to a flood of requests for tutorials and the birth of her popular “Jen & Ink” e-courses.This year, Jennifer added “author” to her list of titles with the release of her debut book, Me & My Ballpoint Pen. She takes us behind the scenes of what it's really like to publish a book - from working with a publisher to navigating the editing process, and opens up about the emotional journey of putting her work into print.Paige and Jennifer dive into a heartfelt conversation about mental health, how finding an approachable creative outlet became a lifeline, and the ways art has helped her focus, heal, and reconnect with herself. If you've ever wondered how to turn a personal creative practice into something that inspires and supports others or what it takes to bring a book idea to life - this episode is a must-listen!

In this episode of The Abstract, Tyler Finn is joined by Tina Hwang, Head of Legal at ClassDojo, whose career spans Google, WhatsApp, Ancestry, and Twitter. She built a career by staying curious, stepping outside her remit, and proactively solving legal and product challenges. She talks about starting out as a commercial attorney, finding her way into privacy and regulatory strategy, and how she learned to lead initiatives without being asked. Tina also shares actionable advice for junior and senior lawyers on navigating career growth, finding the right environments, and redefining legal's value in cross-functional teams.Read detailed summary: https://www.spotdraft.com/podcast/episode-110 Topics Introduction – 00:00Finding fit in the legal profession: from courts to Google—01:05Discovering the business side of legal at Google—04:56From Google to WhatsApp: chasing the excitement of building —07:20Scaling the legal team at WhatsApp: lessons in hiring and growth – 10:44Leadership evolution: from problem solver to team developer – 13:46Mindful management: a four-part framework for legal leaders – 18:54Evaluating new opportunities: people, trust, and executive chemistry – 22:00Building the legal function from scratch at ClassDojo – 25:42People, process, tech: where to start when scaling legal—28:26Metrics that matter: proving legal's impact to the business – 33:10Hiring for adaptability and stage-fit in legal teams – 42:21Rapid-fire Questions – 49:32 Connect with us:Tina Hwang - https://www.linkedin.com/in/tina-hwang-a9556a19/ Tyler Finn - https://www.linkedin.com/in/tylerhfinn SpotDraft - https://www.linkedin.com/company/spotdraft SpotDraft is a leading contract lifecycle management platform that solves your end-to-end contract management issues. Visit https://www.spotdraft.com to learn more.

Donovan PyleHealth Insurance Whistleblower & Author of "Fixing Healthcare: How Executives Can Save Their People, Their Business, and the EconomyDonovan Pyle: Health Insurance Whistleblower Dismantling the $300 Billion Scam. I broke ranks to expose the industry's dirty secrets, and now I'm leading the fight against health insurance and healthcare waste. As a CEO, author, and advocate, I empower businesses to reclaim what's theirs and transform their employee benefits. Ready to expose the truth behind the healthcare insurance racket and find real solutions for change? Let's talk. Hosted on Acast. See acast.com/privacy for more information.

Colleen Robinson And Dana PembertonFounders behind The Digital Dojo, The Black Belt Mind (TBBM), Your Integral Medicine (YIM), NAP (New Agreement Process), and The White Belt MindIn a world where people are struggling to maintain their wellness, navigate trauma, and find their true path to healing, Dana Pemberton and Colleen Robinson are on a mission to change the narrative—one person, one group, and one business at a time!Together, they are the powerhouse duo and Founders of The Digital Dojo, The Black Belt Mind (TBBM), NAP (New Agreement Process) and YIM (Your Integral Medicine). With the collective goal of making wellness, healing, and personal evolution normalised and accessible to everyone.A Powerhouse of Expertise and Experience:Dana, a martial artist turned life coach and consultant, developed the Black Belt Mind as a transformative tool to help individuals and organizations shift their mindset, make empowered choices, and embrace change. Dana's journey from a martial arts dojo owner and athlete to a consultant on change management and personal empowerment is the foundation of The Black Belt Mind. His teachings help individuals navigate challenges with simplicity and power. Hosted on Acast. See acast.com/privacy for more information.

"This month's mix showcases a solid selection of fresh deep and progressive tracks, perfect for some late-night listening 1. Martin Roth - Keep It Movin (Anjunadeep) 2. Danny Howells, Matt Masters - Elevate (Lazy Days) 3. Martin Eyerer, Sergio Parrado - Fiesta Loca [Julian Millan Remix] (Kling Klong Music) 4. Spencer Brown - The Bow (Diviine) 5. Yuvee - Outcome (Anjunadeep Explorations) 6. Dilby - Lost (Sudbeat) 7. Steve Parry - Be Happy (Selador) 8. Remcord - GG (Reba) 9. Lonya - Sadness (Mango Alley) 10. Magitman - Taraazed (Proton Music) 11. D-Nox - Heartbeat (Sprout) 12. Audiojack - Are We Here (8Bit) 13. Kevin Di Serna, Gerbas - Feel It (The Soundgarden) Thank you to the artists and labels for all the amazing music

Featuring an interview with Dr Erika Hamilton, including the following topics: Optimal selection and sequencing of available antibody-drug conjugates for HR-positive metastatic breast cancer (0:00) Bardia A et al. Datopotamab deruxtecan versus chemotherapy in previously treated inoperable/metastatic hormone receptor-positive human epidermal growth factor receptor 2-negative breast cancer: Primary results from TROPION-Breast01. J Clin Oncol 2025;43(3):285-96. Abstract  Pistilli B et al. Datopotamab deruxtecan (Dato-DXd) vs chemotherapy in previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative breast cancer: Final overall survival from the Phase III TROPION-Breast01 trial. ESMO Virtual Plenary 2025;Abstract VP1-2025. First-line use of sacituzumab govitecan in combination with pembrolizumab for advanced triple-negative breast cancer (8:02) Tolaney SM et al. Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in previously untreated PD-L1–positive advanced triple-negative breast cancer (TNBC): Primary results from the randomized phase 3 ASCENT-04/KEYNOTE-D19 study. ASCO 2025;Abstract LBA109. Ongoing trials evaluating datopotamab deruxtecan in earlier lines of therapy (12:06) Dent RA et al. TROPION-Breast02: Datopotamab deruxtecan for locally recurrent inoperable or metastatic triple-negative breast cancer. Future Oncol 2023;19(35):2349-59. Abstract McArthur HL et al. TROPION-Breast04: A randomized phase III study of neoadjuvant datopotamab deruxtecan (Dato-DXd) plus durvalumab followed by adjuvant durvalumab versus standard of care in patients with treatment-naïve early-stage triple negative or HR-low/HER2- breast cancer. Ther Adv Med Oncol 2025;17:17588359251316176. Abstract Bardia A et al. TROPION-Breast03: A randomized phase III global trial of datopotamab deruxtecan ± durvalumab in patients with triple-negative breast cancer and residual invasive disease at surgical resection after neoadjuvant therapy. Ther Adv Med Oncol 2024;16:17588359241248336. Abstract Schmid P et al. TROPION-Breast05: A randomized phase III study of Dato-DXd with or without durvalumab versus chemotherapy plus pembrolizumab in patients with PD-L1-high locally recurrent inoperable or metastatic triple-negative breast cancer. Ther Adv Med Oncol 2025;17:17588359251327992. Abstract Available data with and ongoing trials of sacituzumab tirumotecan for HR-positive, HER2-negative and triple-negative breast cancer (16:53) Yin Y et al. Sacituzumab tirumotecan (sac-TMT) as first-line treatment for unresectable locally advanced/metastatic triple-negative breast cancer (a/mTNBC): Initial results from the phase II OptiTROP-Breast05 study. ASCO 2025;Abstract 1019. Xu B et al. Sacituzumab tirumotecan in patients with previously treated locally recurrent or metastatic triple-negative breast cancer (TNBC): Results from the Phase III Opti-TROP-Breast01 study. ASCO 2024;Abstract 104. Yin Y et al. Sacituzumab tirumotecan in previously treated metastatic triple-negative breast cancer: A randomized phase 3 trial. Nat Med 2025;31(6):1969-1975. Abstract Garrido-Castro AC et al. SACI-IO HR+: A randomized phase II trial of sacituzumab govitecan with or without pembrolizumab in patients with metastatic HR+/HER2-negative breast cancer. ASCO 2024;Abstract LBA1004. CME information and select publications

Rip bits up and stick bits down in today's abstract collage-along with PemaSunday episode of Yoto Daily - the mini podcast from the people at yotoplay.com.If you loved this episode, download the Yoto app to listen to the rest of the week's Yoto Daily episodes for free.If you want to share your artwork with Jake, or contribute your own joke for the Friyay jokes round up, check out yoto.space!Did you know you can tune into Yoto Daily for fun facts and trivia, jokes, and riddles each and every day? Access all episodes of Yoto Daily by downloading the Yoto App. You'll find loads of a world of free kids' radio, and you don't need a Yoto Player to use it.Follow us at @yotoplay on Instagram and Facebook! Hosted on Acast. See acast.com/privacy for more information.

Welcome to Episode 60 of the QR Lab Podcast — Consciousness & the Seven Fields of Reality: From the Abstract to the AbsoluteIn this milestone episode, we dive deep into one of the most profound and mysterious frontiers of human inquiry: consciousness — not just as a state of awareness, but as a multi-dimensional field with complex subdivisions that reflect the very structure of reality itself.We explore a framework of seven interconnected fields that encompass:Mind,Physical Space,Information,Knowledge,Probability,Meaning, andConsciousness itself.This episode focuses specifically on information fields—a concept that forces us to reimagine what reality is, and how mathematics, computation, and even the origin of physical space may emerge from deeper informational substrates.How do abstract fields like probability and meaning interlace with the tangible aspects of our experience? What does it mean to say that information is more fundamental than matter? And how can contemplating these abstract concepts provide pragmatic insights into how we live, perceive, and act in the world?From quantum fields to the architecture of thought, from the metaphysical to the mathematical—we invite you into a bold exercise in abstract exploration with very real implications for your life and our shared reality.Website: https://www.qrlabpod.com/YouTube: https://www.youtube.com/@qrlabpod/shortsInstagram: https://instagram.com/qrlabpodEMAIL: qrlabpod@gmail.comThe unfolding of consciousness isn't just a mystery to be solved—it's a space to be entered. Join us.

Raucous rumblings and club centered grooves are the name of the proverbial game today as we premiere the latest from English imprint, Crescent London. The four tracker adeptly displays a wide array of auditory scope from a duo known as Abstract man. Ranging from the half-time thematic opening through to a thumping finish, it's a well rounded release that works in many situations. Flux, the title track of the release, brings the energy up a notch with steady percussion and bouncing saw-like synths that seem to shift and move through the beginning of the tune. Progressing on, a dark growl starts to emerge providing an aggressive edge that persists and compliments an atonal siren element. Flux and the rest of Abstract Man's release will be released on August 1st. @abstract_man www.instagram.com/abstractman_london/ @crescent-london www.instagram.com/crescent.london/ Write up by @huedj Follow us on social media: @itsdelayed linktr.ee/delayed www.delayed.nyc www.facebook.com/itsdelayed www.instagram.com/_____delayed www.youtube.com/@_____delayed Contact us: info@delayed.nyc

My guest today is Ramtin Naimi. Ramtin is the founder of Abstract Ventures, one of the most talked-about seed funds in Silicon Valley. What makes Ramtin's story so compelling isn't just his firm's remarkable track record—including early investments in Rippling, Solana, and dozens of unicorns—but also the unconventional path he took to get there. From running a hedge fund straight out of high school to filing for bankruptcy at 24, then bootstrapping his way to building a $2 billion AUM venture firm using AngelList and relentless hustle. Our conversation begins in an unexpected place—the art world—where Ramtin has become a sophisticated collector, learning from mentors like Michael Ovitz about market dynamics that surprisingly mirror venture capital. We dive deep into how the art world actually works, and Ramtin explains how these lessons about "masterpieces" apply directly to identifying power-law companies in venture. We go deep on his approach to early-stage investing and how he built Abstract as a co-investment vehicle alongside firms like Sequoia, Benchmark, and Andreessen Horowitz. We explore his portfolio construction model, his philosophy on dilution-sensitive founders, and why he takes upwards of 30 pitch meetings per week to build his "frame of reference." We discuss why Abstract has the highest graduation rate from seed to Series A among all seed funds, and how this competitive advantage compounds over time. This is his first time telling his story, and we discuss the power of pattern recognition, relentless work ethic, and the unique opportunities available to those willing to start from scratch in Silicon Valley. Please enjoy this great conversation with Ramtin Naimi. Colossus Review Profile: Ramtin Naimi For the full show notes, transcript, and links to mentioned content, check out the episode page⁠⁠⁠⁠ ⁠⁠⁠⁠⁠⁠here⁠⁠.⁠⁠⁠⁠⁠⁠⁠⁠ ----- This episode is brought to you by⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Ramp⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠. Ramp's mission is to help companies manage their spend in a way that reduces expenses and frees up time for teams to work on more valuable projects. Go to⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Ramp.com/invest⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ to sign up for free and get a $250 welcome bonus. – This episode is brought to you by⁠⁠⁠⁠⁠⁠ AlphaSense⁠⁠⁠⁠⁠⁠. AlphaSense has completely transformed the research process with cutting-edge AI technology and a vast collection of top-tier, reliable business content. Invest Like the Best listeners can get a free trial now at⁠⁠⁠⁠⁠⁠ Alpha-Sense.com/Invest⁠⁠⁠⁠⁠⁠ and experience firsthand how AlphaSense and Tegus help you make smarter decisions faster. – This episode is brought to you by⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Ridgeline⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠. Ridgeline has built a complete, real-time, modern operating system for investment managers. It handles trading, portfolio management, compliance, customer reporting, and much more through an all-in-one real-time cloud platform. Head to⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ ridgelineapps.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ to learn more about the platform. ----- Editing and post-production work for this episode was provided by The Podcast Consultant (⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠https://thepodcastconsultant.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠). Show Notes: (00:00:00) Welcome to Invest Like the Best (00:05:40) Learning from Mentors and Starting to Collect (00:08:50) Parallels Between Art and Venture Capital (00:12:57) Challenges in Art Collecting (00:20:45) The Role of Status in the Art World (00:25:00) Who Makes the Most Money in the Art World? (00:28:19) Abstract Ventures: Early Stage Investing (00:42:34) Starting a Venture Capital Firm from Scratch (00:43:12) Overcoming Bankruptcy and Early Struggles (00:50:34) Evaluating Technical Capabilities and Momentum (01:02:53) Competing for Deals and Building Relationships (01:15:25) The Role of Brand in Venture Capital (01:22:39) Early Life and Entrepreneurial Beginnings (01:28:40) Starting a Hedge Fund and Learning Hard Lessons (01:31:26) Transition to Venture Capital (01:37:19) Building Abstract and Family Life (01:52:03) The Kindest Thing Anyone Has Done For Ramtin

Black Sabbath "Embryo"Black Sabbath "Children Of The Grave"Melvins "Symptom Of The Universe"Sleep "Snowblind"Graves At Sea "Orchid / Lord Of This World"Cathedral "Wheels Of Confusion"Goatsnake "Who Are You"Eyehategod "Sabbath Jam"Ozzy Osbourne "Mr. Crowley" (Live)

This is a unique space where abstraction encourages us to look beyond what we see, to feel the artist's expression of emotion and imagination formed by using fabric, techniques involving a needle and thread and a whole bucketload of intuition.What does abstraction in embroidery mean?  How do artists use stitches as their expressive tools?  Who are some of the artists working in this arena of embroidery, and what ideas are they exploring?  Finally, how can you begin to embrace embroidery in your unique creative journey?Join me now as I explore this complex yet highly expressive world of abstract embroidery.Show Notes: https://stitchsafari.com/abstract-embroidery/

At the 2025 Kidney Cancer Research Summit hosted by KidneyCAN, CancerNetwork® spoke with a variety of leading experts about key developments in the research and management of kidney cancer. Throughout the meeting, presenters shared their findings related to updated clinical trial results, personalized cancer vaccines, potential biomarkers of interest, and other advancements in the field. Thomas Powles, MBBS, MCRP, MD, discussed outcomes from a quality-adjusted survival time without symptoms or toxicity (Q-TWiST) analysis of the phase 3 LITESPARK-005 trial (NCT04195750), in which investigators evaluated treatment with belzutifan (Welireg) vs everolimus (Afinitor) among patients with advanced renal cell carcinoma (RCC). Powles, a professor of genitourinary oncology, lead for Solid Tumor Research, and director of Barts Cancer Institute at St. Bartholomew's Hospital, Queen Mary University of London, stated that these data demonstrate how belzutifan is more active and better tolerated than everolimus in this patient population. David A. Braun, MD, PhD, assistant professor at Yale School of Medicine and member of the Center of Molecular and Cellular Oncology within the Yale Cancer Center, detailed his presentation on a personalized neoantigen cancer vaccine as a treatment for those with RCC. Based on his presentation, Braun highlighted how neoantigen vaccines may effectively yield T-cell responses in patients, illustrating a need for additional, larger studies to elucidate the clinical activity of this modality in an adjuvant setting. Additionally, Wenxin (Vincent) Xu, MD, a medical oncologist at Dana-Farber Cancer Institute and an assistant professor of medicine at Harvard Medical School, spoke about his presentation on how kidney injury molecule-1 (KIM-1) may serve as a prognostic biomarker of response to therapy in patients with RCC. His research posed questions on how KIM-1 can inform the use of adjuvant therapy or specific therapeutic combinations like nivolumab (Opdivo) plus ipilimumab (Yervoy) for this patient population. Eric Jonasch, MD, gave an overview of his presentation focused on the Kidney Cancer Research Consortium, a research partnership spanning 7 institutions dedicated to facilitating mechanistic, hypothesis-testing clinical trials in RCC. Jonasch, a professor in the Department of Genitourinary Medical Oncology of the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, described how this collaboration aims to link identifiable biological characteristics of RCC subtypes to specific treatment strategies while developing predictive biomarkers. KidneyCAN is a nonprofit organization with a mission to accelerate cures for kidney cancer through education, advocacy, and research funding. You can learn more about KidneyCAN's work here: https://kidneycan.org/ References 1. Powles T, de Velasco G, Choueiri TK, et al. Quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis of belzutifan versus everolimus in previously treated advanced renal cell carcinoma (RCC): LITESPARK-005 (LS-005). Presented at the 2025 Kidney Cancer Research Summit; July 17-18, 2025; Boston, MA. Abstract 13. 2. Braun DA. Personalized vaccines in kidney cancer: a journey from concept to clinic. Presented at the 2025 Kidney Cancer Research Summit; July 17-18, 2025; Boston, MA. 3. Xu W. From bench to bedside: advancing KIM-1 as a tool for clinical decision-making. Presented at the 2025 Kidney Cancer Research Summit; July 17-18, 2025; Boston, MA. 4. Jonasch E. Building the infrastructure for discovery: a clinical trial consortium to accelerate kidney cancer research. Presented at the 2025 Kidney Cancer Research Summit; July 17-18, 2025; Boston, MA.

Welcome to Start The Beat—a podcast documenting the Pittsburgh music scene's past, present, and future. This episode is available on YouTube, Spotify, Apple, and wherever you listen to podcasts. Links available at https://briansikeshowe.com/startthebeat. Start The Beat is proudly sponsored by Hellbender Vinyl.

During our summer break, we are re-airing some of our favorite episodes. What do you do when hope feels lost? Abstract artist Lanecia Rouse Tinsley is no stranger to the hopelessness that comes with grief. In extended isolation because of the pandemic, a nationwide reckoning with race, and our own personal losses, we could all use a bit of what Lanecia calls holy seeing. In this episode, Kate and Lanecia discuss how creativity can be an act of resistance and the hope she discovered on a blank canvas. CW: Miscarriage, death of a child, racism Watch clips from this conversation, read the full transcript, and access discussion questions by clicking here or visiting katebowler.com/podcasts. Follow Kate on Instagram, Facebook, or X (formerly known as Twitter)—@katecbowler. Links to social pages and more available at linktr.ee/katecbowler.See omnystudio.com/listener for privacy information.

“What is the sound of one hand clapping?”— Zen KoanLet's start with a confession.Developing the Unified Behavioral Model (UBM) revealed, in many ways, a side quest I didn't expect: Helping large language models (LLMs) navigate the mental spaghetti we humans lovingly call “logic”—which, if followed faithfully, often leads straight to paradox.You know—the deep, crunchy stuff:Body vs. environmentEmotion vs. feelingSkill vs. habitLogic vs. illogicThese aren't just philosophical speed bumps.They're full-blown conceptual cul-de-sacs.Every time the system—human or machine—hits one, it either freezes or splinters into a dozen confident-but-confused directions.What Is Abstract Thought, Anyway?Get it? To “draw away”It's not about sounding smart or solving puzzles.Frankly, it's your one real edge over AI—for now.It's about seeing things and thinking differently, especially when the pieces don't fit.It's Picasso and Pollock pulling apart realism.It's Einstein “riding a beam of light”.It's Lao Tzu explaining how “The soft and the weak overcome the hard and the strong.”Abstract thinking is cognitive flexibility —it's a different lens to process, beyond logic.It's the ability to zoom out and remove the frame.To hold logic and contradiction in the same hand, without blowing a fuse.So, we deliberately choose to go back to FUNDAMENTALS.Not to simplify, but to clarify.Not to dumb down, but to dissolve—to draw away from false binaries.Because here's the thing about dichotomies: Most aren't real.They're often tradition wrapped in Latin, handed down like sacred scrolls, passed around in conference halls and research papers.They survive not because they're accurate, but because they're familiar.“If you can't explain it simply, you don't understand it well enough.” ~EinsteinAnd that's how the Unified Behavioral Model emerged: Not from divine inspiration, but moderate exasperation.Not from clarity, but from watching both brilliant humans and state-of-the-art LLMs get trapped in mental corners built by… You guessed it: LOGIC.Behaviorally speaking:Is the environment separate from the body?Not really. Both are environmental stimulants.If a headache doesn't change your mood and behavior, just like an idiot screaming at a baseball game, let me know.Are emotions and feelings different?Functionally perhaps? Not elementally. Both relay information.They're conduits—waves influencing your Behavior Echo-System.What about habits and skills?Turns out, they're more alike than different. Both are behaviors shaped through repetition, refined over time until they become automatic. Intentional or not, they're built the same way.How do we reconcile logic and illogic?Reconcile? Even the most “logical” among us do spectacularly irrational things—because we're driven by meaning, by narrative, by the stories we tell ourselves.Logic and illogic aren't separate. They're co-pilots.So if you want to teach a machine how behavior works, we first have to ‘draw away' the various dichotomies logic has constructed.And once those dissolve?The behavior model doesn't need to be built.It simply... emerges.Google: “Why doesn't a unified behavior model exist?”The answer begins with complexity.Complexity created by distinctions (above) that are both very important AND fundamentally (behaviorally speaking), not so important.Like jiggling the old TV antenna for the hundredth time, and suddenly the picture locks in—clear as day, as though it was never scrambled at all.Turns out, it —A UNIFIED BEHAVIOR MODEL—does exist. ☝️It just had to be excavated from under layers of distinctions, logic, and dichotomies.Logic is linear.Behavior, like the human experience, is abstract.This is elemental behavioral literacy. This is the Unified Behavioral Model (UBM)We didn't invent it—we excavated it.It was buried.Habits 2 Goals Premium by Martin Grunburg is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber.“What is your face before your parents were born?” — Zen KoanBecause while machines crunch data, humans connect dots.While models can simulate logic, you can sit with uncertainty.When you can envision a bigger picture, the frames dissolve.“Reflection” (Man Sitting) M. Grunburg 1987Elemental behavioral science shouldn't be reserved for labs and lectures. We teach adolescents the ABCs and 123s —elemental math and grammar. We can, and should, teach elemental behavior. Maybe abstract thinking will come along for the ride.“Experience and knowledge don't arrive with labels, silos, or departments—we create those. Sometimes those distinctions are incredibly useful (like language itself). And sometimes—also like language—they make problem-solving harder than it needs to be.”

Luca Netz, founder of Pudgy Penguins, opens up about surviving crypto's most brutal crashes and building one of the industry's biggest ecosystems.From being down 90% to launching one of crypto's largest airdrop to 6 million wallets, Luca shares the emotional reality of building billion-dollar projects under extreme pressure. The conversation also covers Ethereum Foundation's surprising cultural shift toward builders, Abstract bockchain's competition with Coinbase Base, and why NFTs will make a massive comeback with stablecoin adoption.__________________________________PARTNERS

Can you be too nice to lead?In this episode, Michael Leibovich, GM and Head of Growth at Adobe, shares the career pivots, personal awakenings, and leadership lessons that shaped his unconventional journey from touring musician to executive. Michael opens up about getting fired, receiving feedback that questioned his approach to leadership, and learning how to balance empathy with outcomes. From scaling growth teams at Vimeo, Mindbody, AppFolio, and Abstract to navigating the emotional weight of letting someone go, Michael brings clarity to the messy, human side of leadership.We explore how feedback becomes identity-shaping, what it means to truly “drive clarity” in a role, and why building a career is more about learning from missteps than chasing perfection.In this conversation, you'll learn:Why “you're too nice” was the critique that stuck—and how Michael worked through itThe surprising lesson a failed VP stint taught him about agency and self-worthA simple question that brings clarity to tough calls as a managerThings to listen for:(00:00) Intro(01:24) Growing up in an artistic blue-collar SoCal home(02:30) First jobs and career aspirations(04:29) Journey into music and touring(05:44) Transitioning to tech and SaaS(07:24) How being in a band helped in learning business(11:02) Thank you to our sponsor, ThriveStack(12:20) Being too nice as a leader and finding a balance(21:27) Paying impactful feedback forward(23:38) Navigating imposter syndrome(26:46) Leadership challenges and job insecurity(29:27) Reflecting on career transitions(31:45) A costly mistake and learning experience(36:17) Managing team dynamics as a leader(44:42) A useful shift in perspective(46:46) Driving clarity and embracing intuitionA huge thanks to this episode's sponsor:ThriveStack: Measure Growth. Find Drivers. Fix Leaks. https://www.thrivestack.ai/Resources:Connect with Michael:LinkedIn: https://www.linkedin.com/in/michaelleibovich/ Adobe: https://www.adobe.com Connect with Andrew:LinkedIn: https://www.linkedin.com/in/andrewcapland/ Substack: https://media.deliveringvalue.coHire Andrew as your coach: https://deliveringvalue.co/coaching

Thorn Wych "Ramble In The Bramble"Archimedes Badkar "Wago Gozeze"Sun City Girls "The Venerable Uncle Tompa"Linda Perhacs "Call Of The River"Satomimagae "Uchu"Pelt "Hippy War Machine" 

This week we're excited to bring back Richard Jackson, filmmaker and best friend, to talk about:

HEATHER ECK is a multimedia abstract artist and writer. An intuitive artist and painter, Heather interprets people, places, and experiences through color, a condition known as synesthesia. Like an enormous box of crayons, her gift operates by categorizing through intricate but specific shades of color.  While this condition enables her to experience color, she responds to these encounters with people, things, emotions, and spaces by understanding the particular shade of experience that a person dwells in. She uses her gift to detect the most healing color for them to remedy their wounds. Guided by the chakra system and inspired by spirituality and the mysteries of the universe, Heather transforms these vibrant energies into captivating paintings that uplift, inspire, and, ultimately, heal. Each canvas becomes a symphony of color and emotion, a visual representation of the unseen connections that weave through our lives. Heather's work is more than art; it's a medium of healing, a testament to the profound influence of color on our well-being.

New music from ACTUAL, PROC FISKAL, REX THE DOG, LEON VYNEHALL, CALIBRO 35 + more on this ABSTRACT SCIENCE podcast, hosted by BILL BEARDEN aka WHOA-B + HENRY SELF. BILL begins the program with a mix of jungle + drum n bass. For hour 2, HENRY follows with a clubby set of house, techno, boogie... The post abstract science radio 1373 – whoa-b + henry self appeared first on abstract science >> future music chicago.

The Official Corporate Podcast of Antioch, The Apostolic Church

Welcome to episode 186 of Growers Daily! We cover: prepping soil for heavy feeders, the wild world of rhizosheaths, and sowing a crop into a standing cover crop. We are a Non-Profit! 

Mgła "Exercises In Futility"Robbie Basho "The Grain & The Lotus"Current 93 "The Mystical Body of Christ..."Kyrian's Circle "Kun Puhu Myrskyn Henki"Trees "Ashes"Deathspell Omega "Carnal Malefactor" 

Dr. Diwakar Davar and Dr. Jason Luke discuss novel agents in melanoma and other promising new data in the field of immunotherapy that were presented at the 2025 ASCO Annual Meeting. TRANSCRIPT Dr. Diwakar Davar: Hello. My name is Diwakar Davar, and I am welcoming you to the ASCO Daily News Podcast. I'm an associate professor of medicine and the clinical director of the Melanoma and Skin Cancer Program at the University of Pittsburgh's Hillman Cancer Center. Today, I'm joined by my colleague and good friend, Dr. Jason Luke. Dr. Luke is a professor of medicine. He is also the associate director of clinical research and the director of the Phase 1 IDDC Program at the University of Pittsburgh's Hillman Cancer Center. He and I are going to be discussing some key advancements in melanoma and skin cancers that were presented at the 2025 ASCO Annual Meeting. Our full disclosures are available in the transcript of this episode.  Jason, it is great to have you back on the podcast. Dr. Jason Luke: Thanks again so much for the opportunity, and I'm really looking forward to it. Dr. Diwakar Davar: Perfect. So we will go ahead and start talking a little bit about a couple of key abstracts in both the drug development immunotherapy space and the melanoma space. The first couple of abstracts, the first two, will cover melanoma. So, the first is LBA9500, which was essentially the primary results of RELATIVITY-098. RELATIVITY-098 was a phase 3 trial that compared nivolumab plus relatlimab in a fixed-dose combination against nivolumab alone for the adjuvant treatment of resected high-risk disease. Jason, do you want to maybe give us a brief context of what this is? Dr. Jason Luke: Yeah, it's great, thanks. So as almost all listeners, of course, will be aware, the use of anti–PD-1 immunotherapies really revolutionized melanoma oncology over the last 10 to 15 years. And it has become a standard of care in the adjuvant setting as well. But to review, in patients with stage III melanoma, treatment can be targeted towards BRAF with BRAF and MEK combination therapy, where that's relevant, or anti–PD-1 with nivolumab or pembrolizumab are a standard of care. And more recently, we've had the development of neoadjuvant approaches for palpable stage III disease. And in that space, if patients present, based on two different studies, either pembrolizumab or nivolumab plus ipilimumab can be given prior to surgery for somewhere in the 6- to 9-week range. And so all of these therapies have improved time-to-event endpoints, such as relapse-free or event-free survival. It's worth noting, however, that despite those advances, we've had a couple different trials now that have actually failed in this adjuvant setting, most high profile being the CheckMate-915 study, which looked at nivolumab plus ipilimumab and unfortunately was a negative study. So, with RELATIVITY-047, which was the trial of nivolumab plus relatlimab that showed an improvement in progression-free survival for metastatic disease, there's a lot of interest, and we've been awaiting these data for a long time for RELATIVITY-098, which, of course, is this adjuvant trial of LAG-3 blockade with relatlimab plus nivolumab. Dr. Diwakar Davar: Great. So with that, let's briefly discuss the trial design and the results. So this was a randomized, phase 3, blinded study, so double-blinded, so neither the investigators knew what the patients were getting, nor did the patients know what they were getting. The treatment investigational arm was nivolumab plus relatlimab in the fixed-dose combination. So that's the nivolumab standard fixed dose with relatlimab that was FDA approved in RELATIVITY-047. And the control arm was nivolumab by itself. The duration of treatment was 1 year. The patient population consisted of resected high-risk stage III or IV patients. The primary endpoint was investigator-assessed RFS. Stage and geography were the standard stratifying factors, and they were included, and most of the criteria were balanced across both arms. What we know at this point is that the 2-year RFS rate was 64% and 62% in the nivolumab and nivolumab-combination arms, respectively. The 2-year DMFS rate was similarly equivalent: 76% with nivolumab monotherapy, 73% with the combination. And similar to what you had talked about with CheckMate 915, unfortunately, the addition of LAG-3 did not appear to improve the RFS or DMFS compared to control in this patient population. So, tell us a little bit about your take on this and what do you think might be the reasons why this trial was negative? Dr. Jason Luke: It's really unfortunate that we have this negative phase 3 trial. There had been a lot of hope that the combination of nivolumab with relatlimab would be a better tolerated combination that increased the efficacy. So in the metastatic setting, we do have 047, the study that demonstrated nivolumab plus relatlimab, but now we have this negative trial in the adjuvant setting. And so as to why exactly, I think is a complicated scenario. You know, when we look at the hazard ratios for relapse-free survival, the primary endpoint, as well as the secondary endpoints for distant metastasis-free survival, we see that the hazard ratio is approximately 1. So there's basically no difference. And that really suggests that relatlimab in this setting had no impact whatsoever on therapeutic outcomes in terms of efficacy. Now, it's worth noting that there was a biomarker subanalysis that was presented in conjunction with these data that looked at some immunophenotyping, both from circulating T cells, CD8 T cells, as well as from the tumor microenvironment from patients who were treated, both in the previous metastatic trial, the RELATIVITY-047 study, and now in this adjuvant study in the RELATIVITY-098 study. And to briefly summarize those, what was identified was that T cells in advanced melanoma seemed to have higher expression levels of LAG-3 relative to T cells that are circulating in patients that are in the adjuvant setting. In addition to that, there was a suggestion that the magnitude of increase is greater in the advanced setting versus adjuvant. And the overall summary of this is that the suggested rationale for why this was a negative trial may have been that the target of LAG-3 is not expressed as highly in the adjuvant setting as it is in the metastatic setting. And so while the data that were presented, I think, support this kind of an idea, I am a little bit cautious that this is actually the reason for why the trial was negative, however. I would say we're not really sure yet as to why the trial was negative, but the fact that the hazard ratios for the major endpoints were essentially 1 suggests that there was no impact whatsoever from relatlimab. And this really makes one wonder whether or not building on anti–PD-1 in the adjuvant setting is feasible because anti–PD-1 works so well. You would think that even if the levels of LAG-3 expression were slightly different, you would have seen a trend in one direction or another by adding a second drug, relatlimab, in this scenario. So overall, I think it's an unfortunate circumstance that the trial is negative. Clearly there's going to be no role for relatlimab in the adjuvant setting. I think this really makes one wonder about the utility of LAG-3 blockade and how powerful it really can be. I think it's probably worth pointing out there's another adjuvant trial ongoing now of a different PD-1 and LAG-3 combination, and that's cemiplimab plus fianlimab, a LAG-3 antibody that's being dosed from another trial sponsor at a much higher dose, and perhaps that may make some level of difference. But certainly, these are unfortunate results that will not advance the field beyond where we were at already. Dr. Diwakar Davar: And to your point about third-generation checkpoint factors that were negative, I guess it's probably worth noting that a trial that you were involved with, KeyVibe-010, that evaluated the PD-1 TIGIT co-formulation of vibostolimab, MK-4280A, was also, unfortunately, similarly negative. So, to your point, it's not clear that all these third-generation receptors are necessarily going to have the same impact in the adjuvant setting, even if they, you know, for example, like TIGIT, and they sometimes may not even have an effect at all in the advanced cancer setting. So, we'll see what the HARMONY phase 3 trial, that's the Regeneron cemiplimab/fianlimab versus pembrolizumab control with cemiplimab with fianlimab at two different doses, we'll see how that reads out. But certainly, as you've said, LAG-3 does not, unfortunately, appear to have an impact in the adjuvant setting. So let's move on to LBA9501. This is the primary analysis of EORTC-2139-MG or the Columbus-AD trial. This was a randomized trial of encorafenib and binimetinib, which we will abbreviate as enco-bini going forward, compared to placebo in high-risk stage II setting in melanoma in patients with BRAF V600E or K mutant disease. So Jason, you know, you happen to know one or two things about the resected stage II setting, so maybe contextualize the stage II setting for us based on the trials that you've led, KEYNOTE-716, as well as CheckMate-76K, set us up to talk about Columbus-AD. Dr. Jason Luke: Thanks for that introduction, and certainly stage II disease has been something I've worked a lot on. The rationale for that has been that building off of the activity of anti–PD-1 in metastatic melanoma and then seeing the activity in stage III, like we just talked about, it was a curious circumstance that dating back about 7 to 8 years ago, there was no availability to use anti–PD-1 for high-risk stage II patients, even though the risk of recurrence and death from melanoma in the context of stage IIB and IIC melanoma is in fact similar or actually higher than in stage IIIA or IIIB, where anti–PD-1 was approved. And in that context, a couple of different trials that you alluded to, the Keynote-716 study that I led, as well as the CheckMate 76K trial, evaluated pembrolizumab and nivolumab, respectively, showing an improvement in relapse-free and distant metastasis-free survival, and both of those agents have subsequently been approved for use in the adjuvant setting by the US FDA as well as the European Medicines Agency.  So bringing then to this abstract, throughout melanoma oncology, we've seen that the impact of anti–PD-1 immunotherapy versus BRAF and MEK-targeted therapy have had very similar outcomes on a sort of comparison basis, both in frontline metastatic and then in adjuvant setting. So it was a totally reasonable question to ask: Could we use adjuvant BRAF and MEK inhibitor therapy? And I think all of us expected the answer would be yes. As we get into the discussion of the trial, I think the unfortunate circumstance was that the timing of this clinical trial being delayed somewhat, unfortunately, made it very difficult to accrue the trial, and so we're going to have to try to read through the tea leaves sort of, based on only a partially complete data set. Dr. Diwakar Davar: So, in terms of the results, they wanted to enroll 815 patients, they only enrolled 110. The RFS and DMFS were marginally improved in the treatment arm but certainly not significantly, which is not surprising because the trial had only accrued 16% to 18% of its complete accrual. As such, we really can't abstract from the stage III COMBI-AD data to stage II patients. And certainly in this setting, one would argue that the primary treatment options certainly remain either anti–PD-1 monotherapy, either with pembrolizumab or nivolumab, based on 716 or 76K, or potentially active surveillance for the patients who are not inclined to get treated.  Can you tell us a little bit about how you foresee drug development going forward in this space because, you know, for example, with HARMONY, certainly IIC disease is a part of HARMONY. We will know at least a little bit about that in this space. So what do you think about the stage IIB/C patient population? Is this a patient population in which future combinations are going to be helpful, and how would you think about where we can go forward from here? Dr. Jason Luke: It is an unfortunate circumstance that this trial could not be accrued at the pace that was necessary. I think all of us believe that the results would have been positive if they'd been able to accrue the trial. In the preliminary data set that they did disclose of that 110 patients, you know, it's clear there is a difference at a, you know, a landmark at a year. They showed a 16% difference, and that would be in line with what has been seen in stage III. And so, you know, I think it's really kind of too bad. There's really going to be no regulatory approach for this consideration. So using BRAF and MEK inhibition in stage II is not going to be part of standard practice moving into the future. To your point, though, about where will the field go? I think what we're already realizing is that in the adjuvant setting, we're really overtreating the total population. And so beyond merely staging by AJCC criteria, we need to move to biomarker selection to help inform which patients truly need the treatment. And in that regard, I don't think we've crystallized together as a field as yet, but the kinds of things that people are thinking about are the integration of molecular biomarkers like ctDNA. When it's positive, it can be very helpful, but in melanoma, we found that, unfortunately, the rates are quite low, you know, in the 10% to 15% range in the adjuvant setting. So then another consideration would be factors in the primary tumor, such as gene expression profiling or other considerations.  And so I think the future of adjuvant clinical trials will be an integration of both the standard AJCC staging system as well as some kind of overlaid molecular biomarker that helps to enrich for a higher-risk population of patients because on a high level, when you abstract out, it's just clearly the case that we're rather substantially overtreating the totality of the population, especially given that in all of our adjuvant studies to date for anti–PD-1, we have not yet shown that there's an overall survival advantage. And so some are even arguing perhaps we should even reserve treatment until patients progress. I think that's a complicated subject, and standard of care at this point is to offer adjuvant therapy, but certainly a lot more to do because many patients, you know, unfortunately, still do progress and move on to metastatic disease. Dr. Diwakar Davar: Let's transition to Abstract 2508. So we're moving on from the melanoma to the novel immunotherapy abstracts. And this is a very, very, very fascinating drug. It's IMA203. So Abstract 2508 is a phase 1 clinical update of IMA203. IMA203 is an autologous TCR-T construct targeting PRAME in patients with heavily pretreated PD-1-refractory metastatic melanoma. So Jason, in the PD-1 and CTLA-4-refractory settings, treatment options are either autologous TIL, response rate, you know, ballpark 29% to 31%, oncolytic viral therapy, RP1 with nivolumab, ORR about 30-ish percent. So new options are needed. Can you tell us a little bit about IMA203? Perhaps tell us for the audience, what is the difference between a TCR-T and traditional autologous TIL? And a little bit about this drug, IMA203, and how it distinguishes itself from the competing TIL products in the landscape. Dr. Jason Luke: I'm extremely enthusiastic about IMA203. I think that it really has transformative potential based on these results and hopefully from the phase 3 trial that's open to accrual now. So, what is IMA203? We said it's a TCR-T cell product. So what that means is that T cells are removed from a patient, and then they can be transduced through various technologies, but inserted into those T cells, we can then add a T-cell receptor that's very specific to a single antigen, and in this case, it's PRAME. So that then is contrasted quite a bit from the TIL process, which includes a surgical resection of a tumor where T cells are removed, but they're not specific necessarily to the cancer, and they're grown up in the lab and then given to the patient. They're both adoptive cell transfer products, but they're very different. One is genetically modified, and the other one is not. And so the process for generating a TCR-T cell is that patients are required to have a new biomarker that some may not be familiar with, which is HLA profiling. So the T-cell receptor requires matching to the concomitant HLA for which the peptide is bound in. And so the classic one that is used in most oncology practices is A*02:01 because approximately 48% of Caucasians have A*02:01, and the frequency of HLA in other ethnicities starts to become highly variable. But in patients who are identified to have A*02:01 genotype, we can then remove blood via leukapheresis or an apheresis product, and then insert via lentiviral transduction this T-cell receptor targeting PRAME. Patients are then brought back to the hospital where they can receive lymphodepleting chemotherapy and then receive the reinfusion of the TCR-T cells. Again, in contrast with the TIL process, however, these T cells are extremely potent, and we do not need to give high-dose interleukin-2, which is administered in the context of TIL. Given that process, we have this clinical trial in front of us now, and at ASCO, the update was from the phase 1 study, which was looking at IMA203 in an efficacy population of melanoma patients who were refractory at checkpoint blockade and actually multiple lines of therapy. So here, there were 33 patients and a response rate of approximately 50% was observed in this population of patients, notably with a duration of response approximately a year in that treatment group. And I realize that these were heavily pretreated patients who had a range of very high-risk features. And approximately half the population had uveal melanoma, which people may be aware is a generally speaking more difficult-to-treat subtype of melanoma that metastasizes to the liver, which again has been a site of resistance to cancer immunotherapy. So these results are extremely promising. To summarize them from what I said, it's easier to make TCR-T cells because we can remove blood from the patient to transduce the T cells, and we don't have to put them through surgery. We can then infuse them, and based on these results, it looks like the response rate to IMA203 is a little bit more than double what we expect from lifileucel. And then, whereas with lifileucel or TILs, we have to give high-dose IL-2, here we do not have to give high-dose IL-2. And so that's pretty promising. And a clinical trial is ongoing now called the SUPREME phase 3 clinical trial, which is hoping to validate these results in a randomized global study. Dr. Diwakar Davar: Now, one thing that I wanted to go over with you, because you know this trial particularly well, is what you think of the likelihood of success, and then we'll talk a little bit about the trial design. But in your mind, do you think that this is a trial that has got a reasonable likelihood of success, maybe even a high likelihood of success? And maybe let's contextualize that to say an alternative trial, such as, for example, the TebeAM trial, which is essentially a T-cell bispecific targeting GP100. It's being compared against SOC, investigator's choice control, also in a similarly heavily pretreated patient population. Dr. Jason Luke: So both trials, I think, have a strong chance of success. They are very different kinds of agents. And so the CD3 bispecific that you referred to, tebentafusp, likely has an effect of delaying progression, which in patients with advanced disease could have a value that might manifest as overall survival. With TCR-T cells, by contrast, we see a very high response rate with some of the patients going into very durable long-term benefit. And so I do think that the SUPREME clinical trial has a very high chance of success. It will be the first clinical trial in solid tumor oncology randomizing patients to receive a cell therapy as compared with a standard of care. And within that standard of care control arm, TILs are allowed as a treatment. And so it will also be the first study that will compare TCR-T cells against TILs in a randomized phase 3. But going back to the data that we've seen in the phase 1 trial, what we observe is that the duration of response is really connected to the quality of the response, meaning if you have more than a 50% tumor shrinkage, those patients do very, very well. But even in patients who have less than 50% tumor shrinkage, the median progression-free survival right now is about 4.5 months. And again, as we think about trial design, standard of care options for patients who are in this situation are unfortunately very bad. And the progression-free survival in that population is probably more like 2 months. So this is a trial that has a very high likelihood of being positive because the possibility of long-term response is there, but even for patients who don't get a durable response, they're likely going to benefit more than they would have based on standard chemotherapy or retreatment with an anti–PD-1 agent. Dr. Diwakar Davar: Really, a very important trial to enroll, a trial that is first in many ways. First of a new generation of TCR-T agents, first trial to look at cell therapy in the control arm, a new standard of efficacy, but potentially also if this trial is successful, it will also be a new standard of trial conduct, a new kind of trial, of a set of trials that will be done in the second-line immunotherapy-refractory space. So let's pivot to the last trial that we were going to discuss, which was Abstract 2501. Abstract 2501 is a first-in-human phase 1/2 trial evaluating BNT142, which is the first-in-class mRNA-encoded bispecific targeting Claudin-6 and CD3 in patients with Claudin-positive tumors. We'll talk a little bit about this, but maybe let's start by talking a little bit about Claudin-6. So Claudin-6 is a very interesting new target. It's a target that's highly expressed in GI and ovarian tumors. There are a whole plethora of Claudin-6-targeting agents, including T-cell bispecifics and Claudin-6-directed CAR-Ts that are being developed. But BNT142 is novel. It's a novel lipid nanoparticle LNP-encapsulated mRNA. The mRNA encodes an anti–Claudin-6 CD3 bispecific termed RiboMAB-021. And it then is administered to the patient. The BNT142-encoding mRNA LNPs are taken up by the liver and translated into the active drug. So Jason, tell us a little bit about this agent. Why you think it's novel, if you think it's novel, and let's talk a little bit then about the results. Dr. Jason Luke: So I certainly think this is a novel agent, and I think this is just the first of what will probably become a new paradigm in oncology drug development. And so you alluded to this, but just to rehash it quickly, the drug is encoded as genetic information that's placed in the lipid nanoparticle and then is infused into the patient. And after the lipid nanoparticles are taken up by the liver, which is the most common place that LNPs are usually taken up, that genetic material in the mRNA starts to be translated into the actual protein, and that protein is the drug. So this is in vivo generation, so the patient is making their own drug inside their body. I think it's a really, really interesting approach. So for any drug that could be encoded as a genetic sequence, and in this case, it's a bispecific, as you mentioned, CD3-Claudin-6 engager, this could have a tremendous impact on how we think about pharmacology and novel drug development moving into the future in oncology. So I think it's an extremely interesting drug, the like of which we'll probably see only more moving forward. Dr. Diwakar Davar: Let's maybe briefly talk about the results. You know, the patient population was heavily pretreated, 65 or so patients, mostly ovarian cancer. Two-thirds of the patients were ovarian cancer, the rest were germ cell and lung cancer patients. But let's talk a little bit about the efficacy. The disease control rate was about 58% in the phase 1 population as a whole, but 75% in the ovarian patient population. Now tell us a little bit about the interesting things about the drug in terms of the pharmacokinetics, and also then maybe we can pivot to the clinical activity by dose level. Dr. Jason Luke: Well, so they did present in their presentation at ASCO a proportionality showing that as higher doses were administered, that greater amounts of the drug were being made inside the patient. And so that's an interesting observation, and it's an important one, right? Suggesting that the pharmacology that we classically think of by administering drugs by IV, for example, would still be in play. And that did translate into some level of efficacy, particularly at the higher dose levels. Now, the caveat that I'll make a note of is that disease control rate is an endpoint that I think we have to be careful about because what that really means is sometimes a little bit unclear. Sometimes patients have slowly growing tumors and so on and so forth. And the clinical relevance of disease control, if it doesn't last at least 6 months, I think is probably pretty questionable. So I think these are extremely interesting data, and there's some preliminary sense that getting the dose up is going to matter because the treatment responses were mostly observed at the highest dose levels. There's also a caveat, however, that across the field of CD3 bispecific molecules like this, there's been quite a bit of heterogeneity in terms of the response rate, with some of them only really generating stable disease responses and other ones having more robust responses. And so I think this is a really interesting initial foray into this space. My best understanding is this molecule is not moving forward further after this, but I think that this really does set it up to be able to chase after multiple different drug targets on a CD3 bispecific backbone, both in ovarian cancer, but then basically across all of oncology. Dr. Diwakar Davar: Perfect. This is a very new sort of exciting arena where we're going to be looking at, in many ways, these programmable constructs, whether we're looking at in vivo-generated, in this case, a T-cell bispecific, but we've also got newer drugs where we are essentially giving drugs where people are generating in vivo CAR T, and also potentially even in vivo TCR-T. But certainly lots of new excitement around this entire class of drugs. And so, what we'd like to do at this point in time is switch to essentially the fact that we've got a very, very exciting set of data at ASCO 2025. You've heard from Dr. Luke regarding the advances in both early drug development but also in advanced cutaneous melanoma. And Jason, as always, thank you so much for sharing your very valuable and great, fantastic insights with us on the ASCO Daily News Podcast. Dr. Jason Luke: Well, thanks again for the opportunity. Dr. Diwakar Davar: And thank you to our listeners for taking your time to listen today. You will find the links to the abstracts that we discussed today in the transcript of this episode. And finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. 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. Follow today's speakers:    Dr. Diwakar Davar    @diwakardavar    Dr. Jason Luke @jasonlukemd Follow ASCO on social media:     @ASCO on Twitter       ASCO on Bluesky   ASCO on Facebook       ASCO on LinkedIn   Disclosures:     Dr. Diwakar Davar:      Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences     Consulting or Advisory Role: Instil Bio, Vedanta Biosciences     Consulting or Advisory Role (Immediate family member): Shionogi     Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, GSK, Merck, Arvus Biosciences, Arcus Biosciences     Research Funding (Inst.): Zucero Therapeutics     Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231 Title: COMPOSITIONS AND METHODS FOR TREATING CANCER Applicant: University of Pittsburgh–Of the Commonwealth System of Higher Education Inventors: Diwakar Davar Filing Date: December 11, 2020 Country: United States MCC Reference: 10504-059PV1 Your Reference: 05545; and Application No.: 63/208,719 Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy     Dr. Jason Luke:     Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical, Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX     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, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine     Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, 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., BioNTech AG, Scholar Rock, Next Cure     Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and 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

Dr. Neeraj Agarwal and Dr. Jeanny Aragon-Ching discuss important advances in the treatment of prostate, bladder, and kidney cancers that were presented at the 2025 ASCO Annual Meeting. TRANSCRIPT Dr. Neeraj Agarwal: Hello, and welcome to the ASCO Daily News Podcast. I am Dr. Neeraj Agarwal, your guest host of the ASCO Daily News Podcast today. I am the director of the Genitourinary Oncology Program and a professor of medicine at the University of Utah Huntsman Cancer Institute and editor-in-chief of the ASCO Daily News.  I am delighted to be joined by Dr. Jeanny Aragon-Ching, a GU medical oncologist and the clinical program director of the GU Center at the Inova Schar Cancer Institute in Virginia. Today, we will be discussing some key abstracts in GU oncology that were presented at the 2025 ASCO Annual Meeting.  Our full disclosures are available in the transcript of this episode.  Jeanny, it is great to have you on the podcast. Dr. Jeanny Aragon-Ching: Oh, thank you so much, Neeraj. Dr. Neeraj Agarwal: Jeanny, let's begin with some prostate cancer abstracts. Let's begin with Abstract 5017 titled, “Phase 1 study results of JNJ-78278343 (pasritamig) in metastatic castration-resistant prostate cancer.” Can you walk us through the design and the key findings of this first-in-human trial? Dr. Jeanny Aragon-Ching: Yeah, absolutely, Neeraj. So this study, presented by Dr. Capucine Baldini, introduces pasritamig, a first-in-class T-cell redirecting bispecific antibody that simultaneously binds KLK2 on prostate cancer cells and CD3 receptor complexes on T cells. KLK2 is also known as human kallikrein 2, which is selectively expressed in prostate tissue. And for reference, KLK3 is what we now know as the PSA, prostate-specific antigen, therefore making it an attractive and specific target for therapeutic engagement. Now, while this was an early, first-in-human, phase 1 study, it enrolled 174 heavily pretreated metastatic CRPC patients. So many were previously treated with ARPIs, taxanes, and radioligand therapy. So given the phase 1 nature of this study, the primary objective was to determine the safety and the RP2D, which is the recommended phase 2 dose. Secondary objectives included preliminary assessment of antitumor activity. So, pasritamig was generally well tolerated. There were no treatment-related deaths. Serious adverse events were rare. And in the RP2D safety cohort, where patients received the step-up dosing up to 300 mg of IV every 6 weeks, the most common treatment-related adverse events were low-grade infusion reactions. There was fatigue and grade 1 cytokine release syndrome, what we call CRS. And no cases of neurotoxicity, or what we call ICANS, the immune effector cell-associated neurotoxicity syndrome, reported. Importantly, the CRS occurred in just about 8.9% of patients. All were grade 1. No patients required tocilizumab or discontinued treatment due to adverse events. So, this suggests a favorable safety profile, allowing hopefully for outpatient administration without hospitalization, which will be very important when we're thinking about bispecifics moving forward. In terms of efficacy, pasritamig showed promising activity. About 42.4% of evaluable patients achieved a PSA50 response. Radiographic PFS was about 6.8 months. And among patients with measurable disease, the objective response rate was about 16.1% in those with lymph node or bone metastases, and about 3.7% in those with visceral disease, with a median duration of response of about 11.3 months. So, altogether, this data suggests that pasritamig may offer a well-tolerated and active new potential option for patients with metastatic CRPC.   Again, as a reminder, with the caveat that this is still an early phase 1 study. Dr. Neeraj Agarwal: Thank you, Jeanny. These are promising results for a bispecific T-cell engager, pasritamig, in prostate cancer. I agree, the safety and durability observed here stand out, and this opens the door for further development, possibly even in earlier disease settings.  So, shifting now from immunotherapy to the evolving role of genomics in prostate cancer. So let's discuss Abstract 5094, a real-world, retrospective analysis exploring the prognostic impact of homologous recombination repair gene mutations, especially BRCA1 and BRCA2 mutations, in metastatic hormone-sensitive prostate cancer. Can you tell us more about this abstract, Jeanny? Dr. Jeanny Aragon-Ching: Sure, Neeraj. So this study was presented by Dr. David Olmos, represents one of the largest real-world analyses we have evaluating the impact of homologous recombination repair, or what we would call HRR, alterations in metastatic hormone-sensitive prostate cancer. So, this cohort included 556 men who underwent paired germline and somatic testing. Now, about 30% of patients had HRR alterations, with about 12% harboring BRCA1 or BRCA2 mutations and 16% having alterations in other HRR genes. Importantly, patients were stratified via CHAARTED disease volume, and outcomes were examined across treatment approaches, including ADT alone, doublet therapy, and triplet therapy. The prevalence of BRCA and HRR alterations were about similar between the metastatic hormone-sensitive prostate cancer and the metastatic castrate-resistant prostate cancer, with no differences observed, actually, between the patients with high volume versus low volume disease.  So, the key finding was that BRCA and HRR alterations were associated with poor clinical outcomes in metastatic hormone-sensitive prostate cancer. And notably, the impact of these alterations may actually be even greater in metastatic hormone-sensitive prostate cancer than previously reported in metastatic CRPC. So, the data showed that when BRCA mutations are present, the impact of the volume of disease is actually limited. So, poor outcomes were observed across the board for both high-volume and low-volume groups. So, the analysis showed that patients with HRR alterations had significantly worse outcomes compared to patients without HRR alterations. Median radiographic progression-free survival was about 20.5 months for the HRR-altered patients versus 30.6 months for the non-HRR patients, with a hazard ratio of 1.6. Median overall survival was 39 months for HRR-altered patients compared to 55.7 months for the non-HRR patients, with a hazard ratio of 1.5. Similar significant differences were observed when BRCA-mutant patients were compared with patients harboring non-BRCA HRR mutations. Overall, poor outcomes were independent of treatment of ARPI or taxanes. Dr. Neeraj Agarwal: Thank you, Jeanny. So, these data reinforce homologous recombination repair mutations as both a predictive and prognostic biomarker, not only in the mCRPC, but also in the metastatic hormone-sensitive setting as well. It also makes a strong case for incorporating genomic testing early in the disease course and not waiting until our patients have castration-resistant disease. Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. And I think this really brings home the point and the lead up to the AMPLITUDE trial, which is LBA5006, a phase 3 trial that builds on this very concept of testing with a PARP inhibitor, niraparib, in the hormone-sensitive space. Can you tell us a little bit more about this abstract, Neeraj? Dr. Neeraj Agarwal: Sure. So, the AMPLITUDE trial, a phase 3 trial presented by Dr. Gerhardt Attard, enrolled 696 patients with metastatic hormone-sensitive prostate cancer and HRR gene alterations. 56% of these patients had BRCA1 and BRCA2 mutations. Patients were randomized to receive abiraterone with or without niraparib, a PARP inhibitor. The majority of patients, 78% of these patients, had high-volume metastatic hormone-sensitive prostate cancer, and 87% of these patients had de novo metastatic HSPC. And 16% of these patients received prior docetaxel, which was allowed in the clinical trial. So, with a median follow-up of nearly 31 months, radiographic progression-free survival was significantly prolonged with the niraparib plus abiraterone combination, and median was not reached in this arm, compared to abiraterone alone, which was 29.5 months, with a hazard ratio of 0.63, translating to a 37% reduction in risk of progression or death. This benefit was even more pronounced in the BRCA1 and BRCA2 subgroup, with a 48% reduction in risk of progression, with a hazard ratio of 0.52. Time to symptomatic progression also improved significantly across all patients, including patients with BRCA1, BRCA2, and HRR mutations. Although overall survival data remain immature, early trends favored the niraparib plus abiraterone combination. The safety profile was consistent with prior PARP inhibitor studies, with grade 3 or higher anemia and hypertension were more common but manageable. Treatment discontinuation due to adverse events remained low at 11%, suggesting that timely dose modifications when our patients experience grade 3 side effects may allow our patients to continue treatment without discontinuation. These findings support niraparib plus abiraterone as a potential new standard of care in our patients with metastatic hormone-sensitive prostate cancer with HRR alterations, and especially in those who had BRCA1 and BRCA2 mutations. Dr. Jeanny Aragon-Ching: Thank you, Neeraj. This trial is especially exciting because it brings PARP inhibitors earlier into the treatment paradigm. Dr. Neeraj Agarwal: Exactly. And it is exciting to see the effect of PARP inhibitors in the earlier setting.  So Jeanny, now let's switch gears a bit to bladder cancer, which also saw several impactful studies. Could you tell us about Abstract 4502, an exploratory analysis from the EV-302 trial, which led to approval of enfortumab vedotin plus pembrolizumab for our patients with newly diagnosed metastatic bladder cancer? So here, the authors looked at the outcomes in patients who achieved a confirmed complete response with EV plus pembrolizumab. Dr. Jeanny Aragon-Ching: Sure, Neeraj. So, EV-302 demonstrated significant improvements in progression-free and overall survival for patients previously treated locally advanced or metastatic urothelial cancer, I'll just call it metastatic UC, as a frontline strategy, establishing EV, which is enfortumab vedotin, plus pembro, with pembrolizumab as standard of care in this setting.  So, this year at ASCO, Dr Shilpa Gupta presented this exploratory responder analysis from the phase 3 EV-302 trial. Among 886 randomized patients, about 30.4% of patients, this is about 133, in the EV+P arm, and 14.5% of the patients in the chemotherapy arm, achieved a confirmed complete response. They call it the CCR rates. So for patients who achieved this, median PFS was not reached with EV+P compared to 26.9 months with chemotherapy, with a hazard ratio of 0.36, translating to a 64% reduction in the risk of progression. Overall survival was also improved. So the median OS was not reached in either arm, but the hazard ratio favored the EV+P at 0.37, translating to a 63% reduction in the risk of death. The median duration of complete response was not reached with EV+P compared to 15.2 months with chemotherapy. And among those patients who had confirmed CRs at 24 months, 78% of patients with the EV+P arm remained progression-free, and around 95% of the patients were alive, compared to 54% of patients who were progression-free and 86% alive of the patients in the chemotherapy arm. Safety among responders were also consistent with prior reports. Grade 3 or higher treatment-related adverse events occurred in 62% of EV+P responders and 72% of chemotherapy responders. Most adverse events were managed with dose modifications, and importantly, no treatment-related deaths were reported among those who were able to achieve complete response.  So these findings further reinforce EV and pembro as the preferred first-line therapy for metastatic urothelial carcinoma, offering a higher likelihood of deep, durable responses with a fairly manageable safety profile. Dr. Neeraj Agarwal: Thank you for the great summary, Jeanny. These findings underscore the depth and durability of responses achievable with this combination and also suggest that achieving a response may be a surrogate for long-term benefit in patients with metastatic urothelial carcinoma.  So now, let's move to Abstract 4503, an exploratory ctDNA analysis from the NIAGARA trial, which evaluated perioperative durvalumab, an immune checkpoint inhibitor, in muscle-invasive bladder cancer. So what can you tell us about this abstract? Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. So, in NIAGARA, presented by Dr. Tom Powles, the addition of perioperative durvalumab to neoadjuvant chemotherapy, gem/cis, significantly improved event-free survival, overall survival, and pathologic complete response in patients with cisplatin-eligible muscle-invasive bladder cancer. Recall that this led to the U.S. FDA approval of this treatment regimen on March 28, 2025.  So, a planned exploratory analysis evaluated the ctDNA dynamics and their association with clinical outcomes, which was the one presented recently at ASCO. So, the study found that the incidence of finding ctDNA positivity in these patients was about 57%. Following neoadjuvant treatment, this dropped to about 22%, with ctDNA clearance being more common in the durvalumab arm, about 41%, compared to the chemotherapy control arm of 31%. Notably, 97% of patients who remained ctDNA positive prior to surgery failed to achieve a pathologic CR. So, this indicates a strong association between ctDNA persistence and lack of tumor eradication. So, postoperatively, only about 9% of patients were ctDNA positive. So, importantly, durvalumab conferred an event-free survival benefit regardless of ctDNA status at both baseline and post-surgery. Among patients who were ctDNA positive at baseline, durvalumab led to a hazard ratio of 0.73 for EFS. So, this translates to a 27% reduction in the risk of disease recurrence, progression, or death compared to the control arm. In the post-surgical ctDNA-positive group, the disease-free survival was also improved with a hazard ratio of 0.49, translating to a 51% reduction in the risk of recurrence.  So, these findings underscore the prognostic value of ctDNA and suggest that durvalumab provides clinical benefit irrespective of molecular residual disease status. So, the data also supports that ctDNA is a promising biomarker for future personalized strategies in the perioperative treatment of muscle-invasive bladder cancer. Dr. Neeraj Agarwal: Thank you, Jeanny. It is great to see that durvalumab is improving outcomes in these patients regardless of ctDNA status. However, based on these data, presence of ctDNA in our patients warrants a closer follow-up with imaging studies, because these patients with positive ctDNA seem to have a higher risk of recurrence. Dr. Jeanny Aragon-Ching: I agree, Neeraj.  Let's round out the bladder cancer discussion with Abstract 4518, which reported the interim results of SURE-02, which is a phase 2 study evaluating neoadjuvant sacituzumab govitecan plus pembrolizumab in cisplatin-ineligible muscle-invasive bladder cancer. Can you tell us more about this abstract, Neeraj? Dr. Neeraj Agarwal: Sure, Jeanny. So, Dr Andrea Necchi presented interim results from the SURE-02 trial. This is a phase 2 study evaluating neoadjuvant sacituzumab govitecan plus pembrolizumab, followed by a response-adapted bladder-sparing treatment and adjuvant pembrolizumab in patients with muscle-invasive bladder cancer.  So, in this interim analysis, 40 patients were treated and 31 patients were evaluable for efficacy. So, the clinical complete response rate was 38.7%. All patients achieving clinical complete response underwent bladder-sparing approach with a repeat TURBT instead of radical cystectomy. Additionally, 51.6% of patients achieved excellent pathologic response with a T stage of 1 or less after neoadjuvant therapy. The treatment was well tolerated, with only 12.9% of patients experiencing grade 3 or higher adverse events without needing dose reduction of sacituzumab. Molecular profiling, interestingly, showed that clinical complete response correlated with luminal and genomically unstable subtypes, while high stromal gene expression was associated with lack of response.  These results suggest that sacituzumab plus pembrolizumab combination has promising activity in this setting, and tolerability, and along with other factors may potentially allow a bladder preservation approach in a substantial number of patients down the line. Dr. Jeanny Aragon-Ching: Yeah, agree with you, Neeraj. And the findings are very provocative and support completing the full trial enrollment and further exploration of this strategy in muscle-invasive bladder cancer in order to improve and provide further bladder-sparing strategies. Dr. Neeraj Agarwal: Agree. So, let's now turn to the kidney cancer, starting with Abstract 4505, the final overall analysis from CheckMate-214 trial, which evaluated nivolumab plus ipilimumab, so dual checkpoint inhibition strategy, versus sunitinib in our patients with metastatic clear cell renal cell carcinoma. Dr. Jeanny Aragon-Ching: Yeah, absolutely, Neeraj. So, the final 9-year analysis of the phase 3 CheckMate-214 trial confirms the long-term superiority of nivolumab and ipilimumab over sunitinib for first-line treatment of advanced metastatic renal cell carcinoma. So, this has a median follow-up of 9 years. Overall survival remains significantly improved with the combination. So, in the ITT patient population, the intention-to-treat, the hazard ratio for overall survival was 0.71. So, this translates to a 29% reduction in the risk of death. 31% of patients were alive at this 108-month follow-up compared to 20% only in those who got sunitinib. So, similar benefits were observed in the intermediate- and poor-risk groups with a hazard ratio of 0.69, and 30% versus 19% survival at 108 months.  Importantly, a delayed benefit was also seen in those favorable-risk patients. So, the hazard ratio for overall survival improved from 1.45 in the initial report and now at 0.8 at 9 years follow-up, with 35% of patients alive at 108 months compared to 22% in those who got sunitinib. Progression-free survival also favored the nivo-ipi arm across all risk groups. At 96 months, the probability of remaining progression-free was about 23% compared to 9% in the sunitinib arm in the ITT patient population, 25% versus 9% in the intermediate- and poor-risk patients, and 13% compared to 11% in the favorable-risk patients. Importantly, at 96 months, 48% of patients in the nivo-ipi responders remained in response compared to just 19% in those who got sunitinib. And in the favorable-risk group, 36% of patients who responded remained in response, although data were not available for sunitinib in this subgroup.  So, this data reinforces the use of nivolumab and ipilimumab as a durable and effective first-line effective strategy for standard of care across all risk groups for advanced renal cell carcinoma. Dr. Neeraj Agarwal: Thank you, Jeanny. And of course, since ipi-nivo data were presented, several other novel ICI-TKI combinations have emerged. And I'm really hoping to see very similar data with TKI-ICI combinations down the line. It is really important to note that we are not seeing any new safety signals with the ICI combinations or ICI-based therapies, which is very reassuring given the extended exposure. Dr. Jeanny Aragon-Ching: Absolutely agree with you there, Neeraj.  Now, going on and moving on to Abstract 4514, which is the KEYNOTE-564 trial, and they reported on the 5-year outcomes of adjuvant pembrolizumab in clear cell RCC in patients who are at high risk for recurrence. Can you tell us a little bit more about this abstract, Neeraj? Dr. Neeraj Agarwal: Sure. So, the KEYNOTE-564 trial established pembrolizumab monotherapy as the first adjuvant regimen to significantly improve both disease-free survival and overall survival compared to placebo after surgery for patients with clear cell renal cell carcinoma. So, Dr Naomi Haas presented the 5-year update from this landmark trial.  A total of 994 patients were randomized to receive either pembrolizumab or placebo. The median follow-up at the time of this analysis was approximately 70 months. Disease-free survival remained significantly improved with pembrolizumab. The median DFS was not reached with pembrolizumab compared to 68.3 months with placebo, with a hazard ratio of 0.71, translating to a 29% reduction in risk of recurrence. At 5 years, 60.9% of patients receiving pembrolizumab remained disease-free compared to 52.2% with placebo. Overall survival also favored pembrolizumab. The hazard ratio for OS was 0.66, translating to a 34% reduction in risk of death, with an estimated 5-year overall survival rate of 87.7% with pembrolizumab compared to 82.3% for placebo. Importantly, these benefits were consistent across all key subgroups, including patients with sarcomatoid features. In addition, no new serious treatment-related adverse events have been reported in the 3 years since treatment completion.  So, these long-term data confirm pembrolizumab as a durable and effective standard adjuvant therapy for patients with resected, high-risk clear cell renal cell carcinoma. Dr. Jeanny Aragon-Ching: Thank you for that wonderful summary, Neeraj. Dr. Neeraj Agarwal: That wraps up our kidney cancer highlights. Any closing thoughts, Jeanny, before we conclude? Dr. Jeanny Aragon-Ching: It's been so wonderful reviewing these abstracts with you, Neeraj. So, the 2025 ASCO Annual Meeting showcased a lot of transformative data across GU cancers, from first-in-class bispecifics to long-term survival in RCC. And these findings are already shaping our clinical practices. Dr. Neeraj Agarwal: I agree. And we have covered a broad spectrum of innovations in GU cancers with strong clinical relevance.  So, thank you, Jeanny, for joining me today and sharing your insights.  And thank you to our listeners for joining us. You will find links to the abstracts discussed today in the transcript of this episode. If you find these conversations valuable, please take a moment to rate, review, and subscribe to the ASCO Daily News Podcast wherever you listen. Thank you so much. 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. Neeraj Agarwal     @neerajaiims     Dr. Jeanny Aragon-Ching   Follow ASCO on social media:       @ASCO on Twitter       ASCO on Bluesky   ASCO on Facebook       ASCO on LinkedIn       Disclosures:   Dr. Neeraj Agarwal:   Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb, AstraZeneca, Nektar, Lilly, Bayer, Pharmacyclics, Foundation Medicine, Astellas Pharma, Lilly, Exelixis, AstraZeneca, Pfizer, Merck, Novartis, Eisai, Seattle Genetics, EMD Serono, Janssen Oncology, AVEO, Calithera Biosciences, MEI Pharma, Genentech, Astellas Pharma, Foundation Medicine, and Gilead Sciences  Research Funding (Institution): Bayer, Bristol-Myers Squibb, Takeda, Pfizer, Exelixis, Amgen, AstraZeneca, Calithera Biosciences, Celldex, Eisai, Genentech, Immunomedics, Janssen, Merck, Lilly, Nektar, ORIC Pharmaceuticals, Crispr Therapeutics, Arvinas  Dr. Jeanny Aragon-Ching:   Honoraria: Bristol-Myers Squibb, EMD Serono, Astellas Scientific and Medical Affairs Inc., Pfizer/EMD Serono   Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, MedImmune, Bayer, Merck, Seattle Genetics, Pfizer, Immunomedics, Amgen, AVEO, Pfizer/Myovant, Exelixis,    Speakers' Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb, Astellas/Seattle Genetics

Dr. Vamsi Velcheti and Dr. Nate Pennell discuss novel treatment approaches in small cell and non-small cell lung cancer that were featured at the 2025 ASCO Annual Meeting. TRANSCRIPT Dr. Vamsi Velcheti: Hello, I'm Dr. Vamsi Velcheti, your guest host of the ASCO Daily News Podcast. I'm a professor of medicine and chief of hematology and oncology at the Mayo Clinic in Jacksonville, Florida. The 2025 ASCO Annual Meeting featured some exciting advancements in small cell lung cancer, targeted therapies for non-small cell lung cancer, and other novel [treatment] approaches. Today, I'm delighted to be joined by Dr. Nate Pennell to discuss some of the key abstracts that are advancing the lung cancer field. Dr. Pennell is the co-director of the Cleveland Clinic Lung Cancer Program and also the vice chair of clinical research at the Taussig Cancer Institute. Our full disclosures are available in the transcript of this episode. Nate, it's great to have you back on the podcast. Thanks so much for being here. Dr. Nate Pennell: Thanks, Vamsi. Always a pleasure. Dr. Vamsi Velcheti: Let's get started, and I think the first abstract that really caught my attention was Abstract 8516, “The Randomized Trial of Relevance of Time of Day of Immunotherapy for Progression-Free and Overall Survival in Patients With Non-Small Cell Lung Cancer.” What are your thoughts about this, Nate? Dr. Nate Pennell: I agree. I thought this was one of the most discussed abstracts, certainly in the lung cancer session, but I think even outside of lung cancer, it got some discussion. So, just to put this in perspective, there have been a number of publications that have all been remarkably consistent, and not just in lung cancer but across multiple cancer types, that immunotherapy, immune checkpoint inhibitors, are commonly used. And all of them have suggested, when looking at retrospective cohorts, that patients who receive immune checkpoint inhibitors earlier in the day – so in the morning or before the early afternoon – for whatever reason, appear to have better outcomes than those who get it later in the day, and this has been repeated. And I think many people just sort of assumed that this was some sort of strange association and that there was something fundamentally different from a prognostic standpoint in people who came in in the morning to get their treatment versus those who came later in the afternoon, and that was probably the explanation. The authors of this randomized trial actually decided to test this concept. And so, about 210 patients with previously untreated advanced non-small cell lung cancer were randomly assigned to get chemo and immune checkpoint inhibitor – either pembrolizumab or sintilimab – and half of them were randomly assigned to get the treatment before 3 PM in the afternoon, and half of them were assigned to get it after 3 PM in the afternoon. And it almost completely recapitulated what was seen in the retrospective cohorts. So, the median progression-free survival in those who got earlier treatment was 13.2 months versus only 6.5 months in those who got it later in the day. So, really enormous difference with a hazard ratio of 0.43, which was statistically significant. And perhaps even more striking, the median overall survival was not reached in the early group versus 17.8 months in the late group with a hazard ratio of 0.43, also highly statistically significant. Even the response rate was 20% higher in the early patients; 75% response rate compared to 56% in the late-time-of-day patients. So very consistent across all measures of efficacy with pretty good matched characteristics across the different groups. And so, I have to tell you, I don't know what to make of this. I certainly was a skeptic about the retrospective series, but now we have a prospective randomized trial that shows essentially the same thing. So, maybe there is a difference between getting treated in the morning, although I have yet to hear someone give a very good mechanistic explanation as to why this would be. What were your thoughts on this? Dr. Vamsi Velcheti: It's indeed fascinating, Nate, and I actually think this was a very interesting abstract. Really, I was caught off guard looking at the data. I mean, if it were a drug, we would be so excited, right? I mean, with those kind of survival benefits. I don't know. I think circadian rhythm probably has something to do with it, like different cytokine profiles at the time of administration. I mean, who knows? But I think it's a randomized trial, and I think I would expect to see a mad rush for treatment appointments early in the morning given this, and at least I want my patients to come in first thing in the morning. It'll be interesting to see. Dr. Nate Pennell: It's important to point out that in this study, everyone got chemo and immunotherapy. And, at least in our cancer center, most patients who are getting platinum-doublet chemotherapy and immunotherapy actually do get treated earlier in the day already, just because of the length of the infusion appointment that's needed. So it really is oftentimes people getting single-agent immunotherapy who are often getting the later, shorter visits. But if you have a choice, I think it would be very reasonable to have people treated earlier in the day. And I do think most of the impressions that I got from people about this is that they would like to see it reproduced but certainly well worth further investigation. And I personally would like to see more investigation into what the rationale would be for this because I still can't quite figure out, yes, if you got it at, say, you know, 5 PM, that's later in the day and I can understand that maybe your immune system is somewhat less receptive at that point than it would be in the morning. But because these checkpoint inhibitors have such long half-lives, it's still in your system the next morning when your immune system is supposedly more receptive. So I don't quite understand why that would be the case. Well, let's move on to the next study. I would like to hear your thoughts on Abstract 8515, “Plasma-Guided, Adaptive First-Line Chemoimmunotherapy for Non-Small Cell Lung Cancer.” Dr. Vamsi Velcheti: Yeah, this was another abstract that seems to be really interesting in my opinion. I think there's kind of a lot of emphasis lately on ctDNA and MRD-based assays to monitor disease. In the lung cancer space, we haven't had a lot of clinical trials looking at this prospectively, and this was one of those pilot studies where they looked at circulating free DNA (cfDNA)-based response-adaptive strategy for frontline patients who are PD-L1 positive. So, patients started with pembrolizumab monotherapy, and based on plasma molecular response after 2 cycles, those patients without response received early treatment intensification with a platinum doublet. So the approach essentially was to reduce the chemotherapy exposure in patients who respond to immunotherapy. And only about 17.5% of the patients on the trial received chemotherapy based on lack of molecular response. So, in this trial, what they found was patients with the cfDNA response had a markedly improved PFS of 16.4 months versus 4.8 months. So essentially, like, this is a really nice study to set a foundation on which we have to do larger studies to incorporate molecular markers trying to look at cfDNA response to inform treatment strategy, either escalation or de-escalation strategies. So, I thought it was a very interesting study. Dr. Nate Pennell: Yeah. I mean, we always have this question for patients, “Should they get immunotherapy alone or combined with chemo?” and I think this certainly is intriguing, suggesting that there may be ways you can monitor people and perhaps rescue those that aren't going to respond to single agent. I'd like to see a randomized trial against, you know, this strategy, perhaps against everyone getting, say, chemoimmunotherapy or make sure that you're not potentially harming people by doing this strategy. But I agree, it's time to move beyond just observing that cell-free DNA is prognostic and important and start using it to actually guide treatment. Dr. Vamsi Velcheti: Yeah, and I would just caution though, like, you know, I think we need more data, but, however, it's certainly a very interesting piece of data to kind of help inform future trials. So, there was another abstract that caught my attention, and I think this would be a very interesting abstract in the EGFR space. Abstract 8506, "Patritumab Deruxtecan (HER3-DXd) in Resistant EGFR-Mutant Advanced Non-Small Cell Lung Cancer Patients After Third-Generation EGFR TKI," it's the HERTHENA-Lung02 study. What do you think about the results of this study? Dr. Nate Pennell: Yeah, this was, I would say, very widely anticipated and ultimately a little disappointing, despite being a positive trial. So, these are patients with EGFR-mutant non-small cell lung cancer who have progressed after a third-generation EGFR TKI like osimertinib. This is really an area of major unmet need. We do have drugs like amivantamab in this space, but still definitely an area where essentially patients move from having a highly effective oral therapy to being in the realm of chemotherapy as their best option. So, this HER3 antibody-drug conjugate, patritumab deruxtecan, had some good single-arm data for this. And we're sort of hoping this would become an available option for patients. This trial was designed against platinum-doublet chemotherapy in this setting and with a primary endpoint of progression-free survival. And it actually was positive for improved progression-free survival compared to chemo with a hazard ratio of 0.77. But when you look at the medians, you can see that the median PFS was only 5.8 versus 5.4 months. It was really a modest difference between the two arms. And on the interim analysis, it appeared that there will not be a difference in overall survival between the two arms. In fact, the hazard ratio at the interim analysis was 0.98 for the two arms. So based on this, unfortunately, the company that developed the HER3-DXd has withdrawn their application to the FDA for approval of the drug, anticipating that they probably wouldn't get past approval without that overall survival endpoint. So, unfortunately, probably not, at least for the near future, going to be a new option for these patients. Dr. Vamsi Velcheti: Yeah, I think this is a space that's clearly an unmet need, and this was a big disappointment, I should say. I think all of us were going into the meeting anticipating some change in the standard of care here. Dr. Nate Pennell: Yeah, I agree. It was something that I was telling patients, honestly, that I was expecting this to be coming, and so now, definitely a bit of a disappointment. But it happens and, hopefully, it will still find perhaps a role or other drugs with a similar target. Certainly an active area. Well, let's leave the EGFR-mutant space and move into small cell. There were a couple of very impactful studies. And one of them was Abstract 8006, “Lurbinectedin Plus Atezolizumab as First-Line Maintenance Treatment in Patients With Extensive-Stage Small Cell Lung Cancer, Primary Results from the Phase III IMforte Trial.” So, what was your impression of this? Dr. Vamsi Velcheti: Yeah, I think this is definitely an interesting study, and small cell, I remember those days when we had barely any studies of small cell at ASCO, and now we have a lot of exciting developments in the small cell space. It's really good to see. The IMforte trial is essentially like a maintenance lurbinectedin trial with atezolizumab maintenance. And the study was a positive trial. The primary endpoint was a PFS, and the study showed improvement in both PFS and OS with the addition of lurbinectedin to atezolizumab maintenance. And definitely, it's a positive trial, met its primary endpoint, but I always am a little skeptical of adding maintenance cytotoxic therapies here in this setting. In my practice, and I'd like to hear your opinion, Nate, most patients with small cell after 4 cycles of a platinum doublet, they're kind of really beaten up. Adding more cytotoxic therapy in the maintenance space is going to be tough, I think, for a lot of patients. But also, most importantly, I think this rapidly evolving landscape for patients with small cell lung cancer with multiple new, exciting agents, actually like some FDA-approved like tarlatamab, also like a lot of these emerging therapeutics like I-DXd and other ADCs in this space. You kind of wonder, is it really optimal strategy to bring on like another cytotoxic agent right after induction chemotherapy, or do you kind of delay that? Or maybe have like a different strategy in terms of maintenance. I know that the tarlatamab maintenance trial is probably going to read out at some point too. I think it's a little challenging. The hazard ratio is also 0.73. As I said, it's a positive trial, but it's just incremental benefit of adding lurbi. And also on the trial, we need to also pay attention to the post-progression second-line treatments, number of patients who received tarlatamab or any other investigational agents.  So I think it's a lot of questions still. I'm not quite sure I'd be able to embrace this completely. I think a vast majority of my patients might not be eligible anyway for cytotoxic chemotherapy maintenance right away, but yeah, it's tough. Dr. Nate Pennell: Yeah. I would call this a single and not a home run. It definitely is real. It was a real overall survival benefit. Certainly not surprising that a maintenance therapy would improve progression-free survival. We've known that for a long time in small cell, but first to really show an overall survival benefit. But I completely agree with you. I mean, many people are not going to want to continue further cytotoxics after 4 cycles of platinum-doublet chemo. So I would say, for those that are young and healthy and fly through chemo without a lot of toxicity, I think certainly something worth mentioning. The problem with small cell, of course, is that so many people get sick so quickly while on that observation period after first-line chemo that they don't make it to second-line treatment. And so, giving everyone maintenance therapy essentially ensures everyone gets that second-line treatment. But they also lose that potentially precious few months where they feel good and normal and are able to be off of treatment. So, I would say this is something where we're really going to have to kind of sit and have that shared decision-making visit with patients and decide what's meaningful to them. Dr. Vamsi Velcheti: Yeah, I agree. The next abstract that was a Late-Breaking Abstract, 8000, “Overall Survival of Neoadjuvant Nivolumab Plus Chemotherapy in Patients With Resectable Non-Small Cell Lung Cancer in CheckMate-816.” This was a highly anticipated read-out of the OS data from 816. What did you make of this abstract? Dr. Nate Pennell: Yeah, I thought this was great. Of course, CheckMate-816 changed practice a number of years ago when it first reported out. So, this was the first of the neoadjuvant or perioperative chemoimmunotherapy studies in resectable non-small cell lung cancer. So, just to review, this was a phase 3 study for patients with what we would now consider stage II or stage IIIA resectable non-small cell lung cancer. And they received three cycles of either chemotherapy or chemotherapy plus nivolumab, and that was it. That was the whole treatment. No adjuvant treatment was given afterwards. They went to resection. And patients who received the chemoimmunotherapy had a much higher pathologic complete response rate and a much better event-free survival. And based on this, this regimen was approved and, I think, at least in the United States, widely adopted.  Now, since the first presentation of CheckMate 816, there have been a number of perioperative studies that have included an adjuvant component of immunotherapy – KEYNOTE-671, the AEGEAN study – and these also have shown improved outcomes. The KEYNOTE study with pembrolizumab also with an overall survival benefit. And I think people forgot a little bit about CheckMate-816. So, this was the 5-year overall survival final analysis. And it did show a statistically and, I think, clinically meaningful difference in overall survival with the 3 cycles of neoadjuvant chemo-nivo compared to chemo with a hazard ratio of 0.72. The 5-year overall survival of 65% in the chemo-IO group versus 55% with the chemo alone. So a meaningful improvement. And interestingly, that hazard ratio of 0.72 is very similar to what was seen in the peri-operative pembro study that included the adjuvant component. So, very much still relevant for people who think that perhaps the value of those neoadjuvant treatments might be really where most of the impact comes from this type of approach. They also gave us an update on those with pathologic complete response, showing really astronomically good outcomes. If you have a pathologic complete response, which was more than a quarter of patients, the long-term survival was just phenomenal. I mean, 95% alive at 5 years if they were in that group and suggesting that in those patients at least, the adjuvant treatment may not be all that important.  So, I think this was an exciting update and still leaves very much the open question about the importance of continuing immunotherapy after surgery after the neoadjuvant component. Dr. Vamsi Velcheti: Yeah, I completely agree, Nate. I think the million-dollar question is: “Is there like a population of patients who don't have complete response but like maybe close to complete response?” So, would you like still consider stopping adjuvant IO? I probably would not be comfortable, but I think sometimes, you know, we all have patients who are like very apprehensive of continuing treatments. So, I think that we really need more studies, especially for those patients who don't achieve a complete CR. I think trying to find strategies for like de-escalation based on MRD or other risk factors. But we need more trials in that space to inform not just de-escalation, but there are some patients who don't respond at all to a neoadjuvant IO. So, there may be an opportunity for escalating adjuvant therapies. So, it is an interesting space to watch out for. Dr. Nate Pennell: No, absolutely. Moving to KRAS-mutant space, so our very common situation in patients with non-small cell lung cancer, we had the results of Abstract 8500, “First-Line Adagrasib With Pembrolizumab in Patients With Advanced or Metastatic KRASG12C-Mutated Non-Small Cell Lung Cancer” from the phase 2 portion of the KRYSTAL-7 study. Why was this an interesting and important study? Dr. Vamsi Velcheti: First of all, there were attempts to kind of combine KRASG12C inhibitors in the past with immune checkpoint inhibitors, notably sotorasib with pembrolizumab. Unfortunately, those trials have led to like a lot of toxicity, with increased especially liver toxicity, which was a major issue. This is a phase 2 study of adagrasib in combination with pembrolizumab, and this is a study in the frontline setting in patients with the G12C-mutant metastatic non-small cell lung cancer. And across all the PD-L1 groups, the ORR was 44%, and the median PFS was 11 months, comparable to the previous data that we have seen with adagrasib in this setting. So it's not like a major improvement in clinical efficacy. However, I think the toxicity profile that we were seeing was slightly better than the previous trials in combination with sotorasib, but you still have a fair amount of transaminitis even in the study. At this point, this is not ready for clinical primetime. I don't think we should be using sotorasib or adagrasib in the frontline or even in the second line in combination with checkpoint inhibitors. Combining these drugs with checkpoint inhibitors in the clinical practice might lead to adverse outcomes. So, we need to wait for more data like newer-generation G12C inhibitors which are also being studied in combination, so we'll have to kind of wait for more data to emerge in this space. Dr. Nate Pennell: I agree, this is not immediately practice changing. This is really an attempt to try to combine targeted treatment with immune checkpoint inhibitor. And I agree with you that, you know, it does appear to be perhaps a little bit better tolerated than some of the prior combinations that have tried in this space. The outcomes overall were not that impressive, although in the PD-L1 greater than 50%, it did have a better response rate perhaps than you would expect with either drug alone. And I do think that the company is focusing on that population for a future randomized trial, which certainly would inform this question better. But in the meantime, I agree with you, there's a lot of newer drugs that are coming along that potentially may be more active and better tolerated. And so, I'd say for now, interesting but we'll wait and see. Dr. Vamsi Velcheti: Yeah, so now moving back again to small cell. So, there was a Late-Breaking Abstract, 8008. This is a study of tarlatamab versus chemotherapy as second-line treatment for small cell lung cancer. They presented the primary analysis of the phase III DeLLphi-304 study. What do you think about this? Dr. Nate Pennell: Yeah, I thought this was really exciting. This was, I would say, perhaps the most important lung study that was presented. Tarlatamab is, of course, the anti-DLL3 bispecific T-cell engager compound, which is already FDA approved based on a prior single-arm phase II study, which showed a very nice response rate as a single agent in previously treated small cell lung cancer and relatively manageable side effects, although somewhat unique to solid tumor docs in the use of these bispecific drugs in things like cytokine release syndrome and ICANS, the neurologic toxicities. So, this trial was important because tarlatamab was approved, but there were also other chemotherapy drugs approved in the previously treated space. And so, this was a head-to-head second-line competition comparison between tarlatamab and either topotecan, lurbinectedin, or amrubicin in previously treated small cell patients with a primary endpoint of overall survival. So, a very well-designed trial. And it did show, I think, a very impressive improvement in overall survival with a median overall survival in the tarlatamab group of 13.6 months compared to 8.3 months with chemotherapy, hazard ratio of 0.6. And progression-free survival was also longer at 4.2 months versus 3.2 months, hazard ratio of 0.72. In addition to showing improvements in cancer-related symptoms that were improved in tarlatamab compared to chemotherapy, there was actually also significantly lower rates of serious treatment-related adverse events with tarlatamab compared to chemotherapy. So, you do still see the cytokine release syndrome, which is seen in most people but is manageable because these patients are admitted to the hospital for the first two cycles, as well as a significant number of patients with neurologic side effects, the so-called ICANS, which also can be treated with steroids. And so, I think based upon the very significant improvement in outcomes, I would expect that this should become our kind of standard second-line treatment since it seems to be much better than chemo. However, tarlatamab is definitely a new drug that a lot of places are not used to using, and I think a lot of cancer centers, especially ones that aren't tied to a hospital, may have questions about how to deal with the CRS. So, I'm curious your thoughts on that. Dr. Vamsi Velcheti: Yeah, thank you, Nate. And I completely agree. I think the data looked really promising, and I've already been using tarlatamab in the second-line space. The durability of response and overall, having used tarlatamab quite a bit - like, I participated in some of the early trials and also used it as standard of care - tarlatamab has unique challenges in terms of like need for hospitalization for monitoring for the first few treatments and make sure, you know, we monitor those patients for CRS and ICANS. But once you get past that initial administration and monitoring of CRS, these patients have a much better quality of life, they're off chemotherapy, and I think it's really about the logistics of actually administering tarlatamab and coordination with the hospital and administration in the outpatient setting. It's definitely challenging, but I think it definitely can be done and should be done given what we are seeing in terms of clinical efficacy here. Dr. Nate Pennell: I agree. I think hospital systems now are just going to have to find a way to be able to get this on formulary and use it because it clearly seems to be more effective and generally better tolerated by patients. So, should move forward, I think. Finally, there's an abstract I wanted to ask you about, Abstract 8001, which is the “Neoadjuvant osimertinib with or without chemotherapy versus chemotherapy alone in resectable epidermal growth factor receptor-mutated non-small cell lung cancer: The NeoADAURA Study”. And this is one that I think was also fairly highly anticipated. So, what are your thoughts? Dr. Vamsi Velcheti: You know, I wasn't probably surprised with the results, and I believe we were all expecting a positive trial, and we certainly were handed a positive trial here. It's a phase III trial of osimertinib and chemotherapy or osimertinib in the neoadjuvant space followed by surgery, followed by osimertinib. It's a global phase 3 trial and very well conducted, and patients with stage II to stage IIIB were enrolled in the study. And in the trial, patients who had a neoadjuvant osimertinib with or without chemotherapy showed a significant improvement in major pathologic response rates over chemotherapy alone. And the EFS was also positive for osimertinib and chemotherapy, osimertinib monotherapy as well compared to chemotherapy alone. So overall, the study met its primary endpoint, and I think it sheds light on how we manage our patients with early-stage lung cancer. I think osimertinib, we know that osimertinib is already FDA approved in the adjuvant space, but what we didn't really know is how was osimertinib going to work in the neoadjuvant space. And there are always situations, especially for stage III patients, where we are on the fence about, are these patients already close to being metastatic? They have, like, almost all these patients have micrometastatic disease, even if they have stage III. As we saw in the LAURA data, when you look at the control arm, it was like a very short PFS. Chemoradiation does nothing for those patients, and I think these patients have systemic mets, either gross or micrometastatic disease at onset. So, it's really important to incorporate osimertinib early in the treatment course. And I think, especially for the locally advanced patients, I think it's even more important to kind of incorporate osimertinib in the neoadjuvant space and get effective local control with surgery and treat them with adjuvant. I'm curious to hear your thoughts, Nate. Dr. Nate Pennell: I am a believer and have long been a believer in targeted adjuvant treatments, and, you know, it has always bothered me somewhat that we're using our far and away most effective systemic therapy; we wait until after they go through all their pre-op treatments, they go through surgery, then they go through chemotherapy, and then finally months later, they get their osimertinib, and it still clearly improves survival in the adjuvant setting. Why not just start the osimertinib as soon as you know that the patient has EGFR-mutant non-small cell lung cancer, and then you can move on to surgery and adjuvant treatment afterwards? And I think what was remarkable about this study is that all of these patients almost - 90% in each arm - went to surgery. So, you weren't harming them with the neoadjuvant treatment. And clearly better major pathologic response, nodal downstaging, event-free survival was better. But I don't know that this trial is ever going to show an overall survival difference between neoadjuvant versus just surgery and adjuvant treatment, given how effective the drug is in the adjuvant setting. Nonetheless, I think the data is compelling enough to consider this, certainly for our N2-positive, stage IIIA patients or a IIIB who might be otherwise surgical candidates. I think based on this, I would certainly consider that. Dr. Vamsi Velcheti: Yeah, and especially for EGFR, like even for stage IIIB patients, in the light of the LAURA study, those patients who do not do too well with chemoradiation. So you're kind of delaying effective systemic therapy, as you said, waiting for the chemoradiation to finish. So I think probably time to revisit how we kind of manage these locally advanced EGFR patients. Dr. Nate Pennell: Yep, I agree. Dr. Vamsi Velcheti: Nate, thank you so much for sharing your fantastic insights today on the ASCO Daily News Podcast. It's been an exciting ASCO again. You know, we've seen a lot of positive trials impacting our care of non-small cell lung cancer and small cell lung cancer patients. Dr. Nate Pennell: Thanks for inviting me, Vamsi. Always a pleasure to discuss these with you. Dr. Vamsi Velcheti: And thanks to our listeners for your time today. You will find links to all of the abstracts discussed today in the transcript of the episode. Finally, if you value the insights that you hear from the ASCO Daily News Podcast, please take a moment to rate, review, 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. More on 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   ASCO on BlueSky   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 

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Dr. Shaalan Beg and Dr. Kristen Ciombor discuss practice-changing studies in GI cancers and other novel treatment approaches that were presented at the 2025 ASCO Annual Meeting. Transcript Dr. Shaalan Beg: Hello, I'm Dr. Shaalan Beg, welcoming you to the ASCO Daily News Podcast. I'm a medical oncologist and an adjunct associate professor at UT Southwestern Medical Center in Dallas, Texas. There were some remarkable advances in gastrointestinal cancers that were presented at the 2025 ASCO Annual Meeting, and I'm delighted to be joined by Dr. Kristen Ciombor to discuss some exciting GI data. Dr. Ciombor is the Ingram Associate Professor of Cancer Research and a co-leader of Translational Research and the Interventional Oncology Research Program at the Vanderbilt Ingram Cancer Center. Our full disclosures are available in the transcript of this episode. Dr. Ciombor, it's great to have you on the podcast today. Dr. Kristen Ciombor: Thanks, Dr Beg. It's great to be here. Dr. Shaalan Beg: Alright, let's kick it off. Big year for GI cancers. We'll start off with LBA1. This was the ATOMIC study sponsored by NCI and the National Clinical Trials Network (NCTN) and the Alliance group. This is a randomized study of standard chemotherapy alone or combined with atezolizumab as adjuvant therapy for stage III mismatch repair deficient colorectal cancer. Dr. Kristen Ciombor: I think this study was really definitely practice-changing, as you can tell because it was a Plenary. But I do have some concerns in terms of how we're actually going to implement this and whether this is the final answer in this disease subtype. So, as you said, the patients were enrolled with stage III resected mismatch repair deficient colon cancer, and then they were randomized to either modified FOLFOX6 with or without atezolizumab. And that's where it starts to become interesting because not many of us give FOLFOX for 6 months like was done in this study. Obviously, the study was done over many years, so that was part of that answer, but also the patients received atezolizumab for a total of 12 months. So the question, I think, that comes from this abstract is, is this practical and is this the final answer? I do think that this is practice-changing, and I will be talking to my patients with resected mismatch repair deficient colon cancer about FOLFOX plus atezolizumab. I think the big question is, do these patients need chemotherapy? And can we do a neoadjuvant approach instead? And that's where we don't have all the answers yet. Dr. Shaalan Beg: Yeah, but it has been great to see immunotherapy make its way into the adjuvant space after having made such a big impact in the metastatic space, but still some unanswered questions in terms of the need for chemotherapy and then the duration of therapy, which I guess we'll have to stay tuned in for the next couple of years to to get a lot of those questions answered. Dr. Kristen Ciombor: Yeah, but a big congratulations to the study team, to the NCTN, the NCI. I mean, this is really a great example of federally funded research that needs to continue. So, great job by the study team. The DFS 10% difference is really very large and certainly a practice-changing study. Dr. Shaalan Beg: Yeah, and and sticking with colon cancer, and and this another federally funded study, but this time funded by a Canadian cancer clinical trials group was LBA3510. This is the CHALLENGE study. It's a randomized phase 3 trial of the impact of a structured exercise program on disease-free survival for stage III or high-risk stage II colon cancer. This study got a lot of buzz, a lot of mainstream press coverage, and a lot of discussions on what that means for us for the patients who we're going to be seeing next week in our clinic. What was your takeaway? Dr. Kristen Ciombor: Yeah, this is a really interesting study, and I was so glad to see it presented because this partially answers one of the questions that patients always have for us in clinic, right? You know, once they've completed their standard chemotherapy and surgery, what else can they do to help prevent recurrence? And so we've always known and sort of extrapolated that healthy lifestyle habits are good, but now we have data, particularly in these patients. Most of them were stage III colon cancer patients, those had high-risk stage II cancer. And basically, the goal was to increase their physical activity by at least 10 MET hours per week. So, my big question, of course, as I came into this presentation was, “Okay, what does that mean exactly? How does that translate to real life?” And really what the author presented and explained was that basically most patients could hit their target by adding a 45- to 60-minute brisk walk 3 to 4 times a week. So I think this is very approachable.  Now, in the confines of the study, this was a structured exercise program, so it wasn't just patients doing this on their own. But I do think kind of extrapolating from that, that this is very achievable for most patients. And not only did this prevent recurrence of their prior cancer, but actually the rate of new primary cancer diagnoses, was less, which is really interesting, especially in the breast and prostate cancer. So this was a really interesting, and I think practice-changing study as well, especially given that this is something that most patients can do. Dr. Shaalan Beg: Yeah, and there was a lot of discussion in the hallways after the presentation in terms of how this really changes our existing practice because most folks already recommend exercise as a way for improving outcomes in cancer patients. So we've already been doing that. Now we have some data on how much it can impact the benefit. But there was some discussion about what the actual degree of impact was. There was a drop-off rate in terms of how long folks were able to stick with this exercise regimen. But you've seen this in clinic when someone have their surgery, they have their chemotherapy, they've been so intimately involved with the oncology world, with the oncology practice, and they somehow feel that they're being let loose into this mean, angry world without any guidance and they're looking for something to do. “What more can I do in terms of my lifestyle?” And then here we have very solid data, as solid as can be for an intervention like exercise, showing that there is an impact and you can give a prescription for exercise when someone wraps up their chemotherapy for colon cancer, thanks to the study. Dr. Kristen Ciombor: Yeah. It was a great study. Dr. Shaalan Beg: Moving to gastroesophageal cancer, another late-breaking abstract. This is LBA5. The MATTERHORN trial was a phase 3 trial of durvalumab plus FLOT for resectable GE junction and gastric cancer. And again, another area where immunotherapy has made an impact, and here we're seeing it move closer for earlier-stage disease. What was your take-home for the MATTERHORN trial? Dr. Kristen Ciombor: Yeah, so this study looked at neoadjuvant perioperative durvalumab plus our current standard chemotherapy of FLOT versus placebo plus FLOT. And this was a large study, almost 1,000 patients were randomized. And the primary endpoint was event-free survival, and it was definitely met in favor of the D + FLOT arm, as Dr. Klempner discussed after Dr Janjigian's presentation. I do think there are still some unanswered questions here. Overall survival is not yet mature, so we do have to wait and see how that shakes out. But it's very interesting and kind of is reflective of what, as you said, we're looking at earlier and earlier lines of therapy, particularly with immunotherapy, in these GI cancer spaces. So it makes a lot of sense to test this and and to look at this. So the toxicity was pretty similar to what we would expect. Primary endpoint was met, but again, we'll have to wait and see what the survival data looks like. Dr. Shaalan Beg: Yeah, and in oncology, we know, especially for treatment that does add additional cost, it does add additional potential toxicity that we want to see that overall survival nudged. I did see some polls on social media asking folks whether their practices changed from this, and I think the results were favoring adding durvalumab for this group of patients but understanding that there are caveats to the addition of treatments and the eventual FDA approval in that indication as well. Dr. Kristen Ciombor: Exactly. I completely agree with that. Dr. Shaalan Beg: All right. How about we stick with gastroesophageal cancer? LBA4002 was trastuzumab deruxtecan versus ramucirumab plus paclitaxel for second-line treatment in HER2-positive unresectable or metastatic gastric cancer or GE junction cancer. This was the DESTINY-Gastric04 study. And again, antibody-drug conjugates making a big impact across different diseases. And here we have more data in the HER2-positive gastric cancer space. Your thoughts on this study? Dr. Kristen Ciombor: Yeah, so this is a really important space in gastroesophageal cancer because the HER2 positivity rate is fairly high as compared to some of our other tumor types. So, I do think one of the important things was that patients did have biopsy confirmation of HER2 status, which was very important, and then they were randomized to either T-DXd versus the kind of second-line standard of ramucirumab-paclitaxel. So this was a great practical study and really answers a question that we had for a while in terms of does anti-HER2 therapy in the second-line really impact and improve survival. So we did see a statistically significant improvement favoring T-DXd. I do think it's always important to look at toxicity, though, too. And there was about almost 14% rate of interstitial lung disease, which of course is the most feared toxicity from some of these antibody-drug conjugates, especially T-DXd. So I do think it's important to keep that in mind, but this is definitely a great addition to the armamentarium for these HER2-positive patients. Dr. Shaalan Beg: And pancreas cancer was on the stage after a very long time with a positive clinical trial. This is Abstract 4006. These were preliminary results from a phase 2 study of elraglusib in combination with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel alone for previously untreated metastatic pancreas cancer. This is a frontline clinical trial of gemcitabine/nab-paclitaxel plus/minus the study drug. There were other cohorts in this study as well, but they reported the results of their part 3B arm. And great to see some activity in the pancreas space. And your thoughts? Dr. Kristen Ciombor: Yeah, we definitely need better treatments in pancreas cancer. This was a very welcome presentation to see. The elraglusib is an inhibitor of GSK-3beta, and it's thought that that mediates drug resistance and EMT. And so this is, I think, a perfect setting to test this drug. So patients basically were randomized. Patients with metastatic pancreas cancer were randomized 2: 1 to gemcitabine/nab-paclitaxel plus or minus this elraglusib. So, what we saw was that overall survival was better with the addition of this new drug. And overall, not only the 1-year overall survival, but also median overall survival.  The thing that was interesting, though, was that we saw that the overall survival rates were 9.3 months with the combination versus 7.2 months with just gemcitabine/nab-paclitaxel. And that's a little bit lower than we've seen in other studies. So, not sure what was going on there. Was it the patients that were a bit sicker? Was it a patient selection, you know, thing? I'm not really sure how to explain that so much. Also, the toxicity profile was much higher in terms of visual impairment, with over 60% of patients being treated with the combination versus 9% with gemcitabine/nab-paclitaxel. So these were mild, grade 1 and 2, but still something to be cautious about. Dr. Shaalan Beg: And especially with this being a phase 2 trial, making sure that in a larger study we're able to better evaluate the toxicity and see if the control arm in the larger confirmatory study performs differently will be really important before this compound makes it to the clinic in our space. But very exciting to see these kinds of results for pancreas adenocarcinoma. Dr. Kristen Ciombor: Yeah. Dr. Shaalan Beg: We've talked, it seems, a couple of times on this podcast about the BREAKWATER clinical trial. We did hear PFS and updated OS data, updated overall survival data on first-line encorafenib plus cetuximab plus modified FOLFOX6 for BRAF-mutated colorectal cancer. This was LBA3500. And eagerly anticipated results – we have all previously heard the progression-free survival results – but here we heard updated overall survival results, and very well-received study it seemed from the audience that time. So what are your takeaways on the updated results for BREAKWATER? Dr. Kristen Ciombor: In my opinion, this was one of the most practice-confirming studies. As you mentioned, we've already seen some of the preliminary data of BREAKWATER at prior meetings. But really what was particularly impactful for me was the median overall survival with the BREAKWATER regimen. So, again, patients received FOLFOX, encorafenib cetuximab in the first line if they had BRAF-mutated V600E-mutated colorectal cancer. And the median PFS was 12.8 months, which was actually really remarkable in this traditionally very aggressive, poor prognosis subtype of tumors. So, by seeing a median overall survival of 30.3 months was just incredible, in my opinion. Just a few years ago, that was considered the median overall survival for all comers for metastatic colorectal cancer. And we know the median overall survival was more in the less than 12 months range for BRAF. So this was incredibly impactful, and I think should be absolutely practice-changing for anyone who is eligible for this regimen.  I think again, where the practice meets the study is what's kind of important to think about too, how long did patients get FOLFOX, and certainly it adds toxicity to add a BRAF-targeted regimen on top of FOLFOX already. So, one of the other interesting things about the study, though, was that even though it didn't complete treatment, they actually did look at encorafenib/cetuximab alone and in the first line without chemotherapy. And those preliminary results actually looked okay, especially for patients who might not be able to tolerate chemotherapy, which we certainly see in practice. So, overall, definitely more data. And I agree that it's certainly practice-changing. Dr. Shaalan Beg: And it completely, as you mentioned, changes the outlook for a person who's diagnosed with BRAF-mutated metastatic colon cancer today versus even 7 or 8 years ago. Dr. Kristen Ciombor: And we're seeing this over and over in other subtypes too, but how you choose to treat the patient up front really matters. So really giving the right regimen up front is the key here. Dr. Shaalan Beg: And along the same lines, Abstract 3501 wanted to answer the question on whether people with MSI-high metastatic colorectal cancer need double checkpoint inhibitor therapy or is single therapy enough. So this [CheckMate-8HW] study compared nivo plus ipi with nivo alone, nivo monotherapy for MSI-high metastatic colorectal cancer. And we've known that both of these are fairly active regimens, but we also know the chance of immune-related adverse events is significantly higher with combination therapy. So this was a much-needed study for this group of patients. And what were your takeaways here? Dr. Kristen Ciombor: This, of course, has been really nivo-ipi in the first-line MSI-high metastatic colorectal cancer is now a standard of care. And not everybody is eligible for it, and there could be reasons, toxicity reasons, and other things too. But as we've been seeing for the last couple of years, immunotherapy clearly beats chemo in this space. And now looking at doublet versus single immunotherapy treatment in the first line, I think really nivo-ipi does beat out monotherapy. I will say, however, there is a caveat in that we still haven't seen the nivo-ipi versus nivo in the first line. So what has been presented thus far has been across all lines of therapy, and that does muddy the waters a little bit. So definitely looking forward and and we've asked this many times and based on the statistical plan and and what not, you know, we just haven't seen that data yet. But I do think it's becoming increasingly important to consider doublet immunotherapy for these patients as long as there are no contraindications. With the again, with the caveat that we have to have these toxicity discussions in the clinic with patients because many patients can tolerate it, you know, this regimen fairly well, but there can be very severe toxicities. So, I think an informed discussion should really be had with each patient before moving forward. Dr. Shaalan Beg: Yeah, informed decision, making them aware of the potential of real significant toxicities, immune-related toxicities with double therapy. But I am curious in your practice, how often do you see people choosing doublet therapy as frontline? Dr. Kristen Ciombor: So patients are really savvy, and a lot of times they've heard this data before or have come across it in patient advocacy groups and other things, and it's really nice to be able to have that conversation of the risk versus benefit. So I will say not all of my patients choose doublet, and many of them are still cured with immunotherapy monotherapy. So the big question there is, will we ever understand who actually needs the doublet versus who can still be cured or have very good long-term outcomes with just the single agent? And that has not been answered yet. Dr. Shaalan Beg: What a great point. So the last abstract I was hoping we could talk about is POD1UM-303 or the INTERAACT2 subgroup analysis and impact of delayed retifanlimab treatment for patients with squamous cell carcinoma of the anal canal. What were your thoughts here? Dr. Kristen Ciombor: This was a study, actually we saw at ESMO, we saw the primary data at ESMO last year, and this was an update with some exploratory analyses. But this was really an important study because once again, we're looking at immunotherapy in later lines of therapy. That's how we started looking at and investigating immunotherapy, and now we're moving it up and up in the treatment course. So this was a study of carboplatin/paclitaxel plus or minus retifanlimab. Actually it was retifanlimab versus placebo. And it was a positive study, as we heard last year. This actually led to FDA approval of this regimen last month, just before ASCO, and it has now been incorporated in the NCCN guidelines as the preferred first-line option.  So what I thought was important from the additional data presented at ASCO was looking at the different subgroups, it did not appear that patients with liver mets or not had different outcomes. So that was really good to see because sometimes in colon cancer we see that immunotherapy doesn't work as well when patients have liver mets. And interestingly, because we use immunotherapy in anal cancer without any biomarkers, unlike with colon cancer or some of the other tumor types, also the authors looked at PD-L1 status, and it did look like maybe patients did a little bit better if they had higher PD-L1 expression, but patients still could benefit even if they were PD-L1 negative. So that was important, I think, and we will continue to see further data come out from this study. I want to mention also that EA2176 just completed accrual, so that was carbo-taxol plus or minus nivolumab. And so we should be seeing that data sometime soon, which will hopefully also confirm the ongoing role for immunotherapy in the first-line setting for anal cancer. Dr. Shaalan Beg: That was a fantastic review. Thank you, Dr Ciombor. Thanks for sharing your valuable insights with us today on the ASCO Daily News Podcast. Dr. Kristen Ciombor: Thanks for having me here. Dr. Shaalan Beg: And thank you to our listeners for your time today. You will find links to the abstracts discussed today in the transcript of this episode. And if you value the insights that you hear on the podcast, please take a moment to rate, review, and subscribe, wherever you get your podcasts. 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. More on today's speakers:   Dr. Shaalan Beg  @ShaalanBeg  Dr. Kristen Ciombor @KristenCiombor Follow ASCO on social media:    @ASCO on Twitter   @ASCO on BlueSky  ASCO on Facebook    ASCO on LinkedIn    Disclosures:   Dr. Shaalan Beg:   Consulting or Advisory Role: Ipsen, Cancer Commons, Foundation Medicine, Science37, Nant Health, Lindus Health Speakers' Bureau: Sirtex Research Funding (Inst.): Delfi Diagnostics, Universal Diagnostics, Freenome Dr. Kristen Ciombor: Consulting or Advisory Role: Pfizer, Incyte, Exelixis, Bayer, ALX Oncology, Tempus, Agenus, Taiho Oncology, Merck, BeiGene Research Funding (Inst.): Pfizer, Boston Biomedical, MedImmune, Onyx, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Merck, Novartis, Incyte, Amgen, Sanofi, Bristol-Myers Squibb, Array BioPharma, Incyte, Daiichi Sankyo, Nucana, Abbvie, Merck, Pfizer/Calthera, Genentech, Seagen, Syndax Travel, Accommodations, Expenses: Incyte, Tempus

Dr. John Sweetenham and Dr. Marc Braunstein highlight top research on hematologic malignancies from the 2025 ASCO Annual Meeting, including abstracts on newly diagnosed chronic phase CML, relapsed B-cell lymphoma, and multiple myeloma. Transcript Dr. John Sweetenham: Hello, and welcome to the ASCO Daily News Podcast. I'm your host, Dr. John Sweetenham. On today's episode, we'll be discussing promising advances in newly diagnosed chronic phase CML, relapsed B-cell lymphoma, multiple myeloma, and other hematologic malignancies that were presented at the 2025 ASCO Annual Meeting. Joining me for this discussion is Dr. Marc Braunstein, a hematologist and oncologist at the NYU Perlmutter Cancer Center. Our full disclosures are available in the transcript of this episode.  Marc, there were some great studies in the heme space at this year's Annual Meeting, and it's great to have you back on the podcast to highlight some of these advances. Dr. Marc Braunstein: Yes, I agree, John, and thank you so much for inviting me again. It's great to be here.  Dr. John Sweetenham: Let's start out with Abstract 6501. This was a study that reported on the primary endpoint results of the phase 3B ASC4START trial, which assessed asciminib versus nilotinib in newly diagnosed chronic phase CML. And the primary endpoint of this, as you know, was time to treatment discontinuation because of adverse events. Can you give us your insights into this study? Dr. Marc Braunstein: Absolutely. So, like you mentioned, you know, asciminib is an allosteric inhibitor of the BCR-ABL kinase that has activity in CML, and that includes patients with the T315I mutation that confers resistance to first- and second-generation TKIs. So, the ASC4FIRST study, which was published last year in the New England Journal of Medicine, showed superior efficacy of asciminib compared to investigator-selected first- or second-generation TKIs, actually leading to the FDA approval of asciminib in first-line CML. So, the authors of that study presented data at this year's ASCO meeting from the phase 3 ASC4START comparing safety and time to discontinuation due to adverse events of asciminib versus nilotinib, a second-generation TKI. So, 568 patients with newly diagnosed CML were randomized one-to-one to once-daily asciminib or twice-daily nilotinib. So, at a median follow-up of 9.7 months, about 11% in the asciminib group and 17% in the nilotinib group discontinued treatment, with significantly fewer discontinuations with asciminib due to adverse events. There was also a secondary endpoint of major molecular response, which was also better with asciminib. For example, the MR 4.5, which is a deep response, was 2.5% versus 0.4% favoring asciminib by week 12. So, I think in conclusion, these results build on the ASC4FIRST study, making the case for the superior safety and efficacy of asciminib versus other first- or second-generation TKIs in newly diagnosed CML. Dr. John Sweetenham: Thanks, Marc. Do you think this is going to change practice? Dr. Marc Braunstein: I think so. I think there are still some questions to be answered, such as what resistance mutations occur after first-line treatment with asciminib. But I think the sum of these studies really make the case for using asciminib upfront in CML. Dr. John Sweetenham: Okay, great. Thank you. And let's move on to our second abstract. This was Abstract 7015 and was reported from Mass General Hospital. And this was a study in patients with relapsed and refractory diffuse large B-cell lymphoma and reported the 2-year results of the so-called STARGLO study. This is a comparison of glofitamab, a T-cell engaging bispecific antibody, with gemcitabine and oxaliplatin in this group of patients. Can you tell us a little bit about your impressions of this study? Dr. Marc Braunstein: Absolutely. So just for background, the treatment landscape for relapsed/refractory large B-cell lymphoma is expanding, now with two bispecific antibodies targeting CD20 that are approved after two or more lines of therapy. Among these, glofitamab was approved in 2023 based on phase 2 data showing an objective response rate of 52%, with 39% complete responses in relapsed/refractory large B-cell lymphoma patients after a median of three prior lines of therapy. Distinguishing glofitamab from epcoritamab, the other approved bispecific, glofitamab was given for 12 cycles and then stopped. Additionally, when combined with gemcitabine and oxaliplatin in the phase 3 STARGLO study, there was significantly improved overall survival compared to rituximab plus gemcitabine and oxaliplatin in transplant-ineligible relapsed/refractory large B-cell lymphoma patients at a median follow-up of 11 months.  The authors of that study published last year in Lancet now present at ASCO this year the 2-year follow-up of the STARGLO study. Two hundred and seventy-four patients with a median of one prior line of therapy were randomized two-to-one to glofitamab plus GemOx versus rituximab plus GemOx, with the primary endpoint of overall survival. Here, the median overall survival was not reached versus 13.5 months, with a median PFS also significantly improved at about 14 months versus 4 months in the control. CRS of note in the glofitamab arm was mostly grade 1 or 2, with only about 2.3% grade 3 events. And three of the four patients had grade 1 or 2 neurotoxicity. So, John, putting this into context, I think it's encouraging that we now have randomized data showing the superiority of a bispecific plus chemotherapy over rituximab plus chemotherapy in transplant-ineligible patients. And while only 8% of the patients in the STARGLO study had prior anti-CD19 CAR T-cell therapy, I think this regimen could be considered in those patients who are ineligible for transplant or CAR T-cell therapy. Dr. John Sweetenham: Yeah, I agree. I think a couple of other compelling numbers to me were the fact that around 55% of these patients were alive at 2 years in the group who'd received glofitamab, and that almost 90% of those having that arm of the study who had a CR at the end of treatment were alive at 12 months. So, clearly, it's an active agent and also a kind of great off-the-shelf fixed-duration alternative in these relapsed and refractory patients. Dr. Marc Braunstein: I agree, and I would also note that the phase 3 SKYGLO study is looking at glofitamab plus Pola-R-CHP versus Pola-R-CHP alone. So, we may even be using these eventually in the first-line setting. Dr. John Sweetenham: Absolutely. Let's stay on the theme of diffuse large B-cell lymphoma and look at one other abstract in that space, which was Abstract 7000. This was a study from the HOVON group in the Netherlands, which looked at the prospective validation of end-of-treatment circulating tumor DNA in the context of a national randomized trial. What are your thoughts on this? Dr. Marc Braunstein: So, non-invasive liquid biopsies to detect and monitor cancers via circulating tumor-derived DNA or ctDNA, you know, is really emerging as a valuable tool in both solid and liquid tumors to understand disease biology, and also for drug development. So, to date, the most established application of ctDNA in lymphoma, I would say, is really for monitoring of minimal residual disease. So, in this correlative study by Steven Wang and colleagues in the HOVON group, they evaluated the prognostic significance of MRD status as assessed by ctDNA following first-line treatment with curative intent with either R-CHOP or dose-adjusted R-EPOCH. At the end of treatment, encouragingly, 76% of patients were MRD-negative, and 24% were MRD-positive. Now, of note, MRD-positive status at the end of treatment predicted inferior progression-free survival at 2 years, with only 28% of patients who are MRD-positive being progression-free versus 88% who are MRD-negative. And in fact, all the patients who failed to achieve a complete response after first-line treatment and were MRD-positive ultimately relapsed. So, circulating tumor cells are rarely found in large B-cell lymphomas, and so this study really builds on accumulating data that ctDNA has clinical value to detect residual disease with a non-invasive approach. So, there are many implications of how we could potentially use this to detect early signs of relapse, to potentially escalate treatment for consolidation if patients remain MRD-positive. So, I think this will eventually become utilized in clinical practice. Dr. John Sweetenham: Yeah, I agree. I think it's interesting that it provided an independent assessment of response, which was independent, in fact, of the results of PET-CT scanning and so on, which I think was very interesting to me. And the authors of the abstract actually commented in their presentation that they think this should be integrated as part of the standard response assessment now for patients with large B-cell lymphoma. Would you agree with that? Dr. Marc Braunstein: I would. For one thing, it allows repeated sampling. It's a non-invasive approach; it doesn't necessarily require a bone marrow biopsy, and it may have more sensitivity than conventional response measures. So, I think having a standardized system to assess ctDNA will be helpful, and definitely, I think this will be a valuable biomarker of disease response. Dr. John Sweetenham: Okay, great. Thanks. We're going to change gear again now, and we're going to highlight two abstracts in the multiple myeloma space. The first one of these is Abstract 7507. And this abstract reported on the long-term results of the CARTITUDE study for patients with relapsed and refractory multiple myeloma. What are your comments on this presentation? Dr. Marc Braunstein: So, this study actually got a lot of press, and I've already had multiple patients asking me about CAR T-cells as a result. Just as some background, CAR T-cells targeting BCMA, which is pretty much universally expressed on malignant plasma cells in myeloma, have really shown remarkable responses, especially in heavily pretreated patients, showing superior progression-free survival in both later and earlier phases of the disease, including in randomized studies in patients with second-line or beyond. So, the CARTITUDE-1 was really the original Phase 1/2 study of ciltacabtagene autoleucel, one of the two approved anti-BCMA CAR T-cell products, which was investigated in patients with a median of six to seven prior lines of therapy. So, these were patients who were pretty heavily pretreated. So, in the study presented by Voorhees at this year's ASCO meeting, this was the long-term follow-up at a median of 5 years from the one-time CAR infusion in these patients with a median of five prior lines of therapy. And remarkably, of the 97 patients, 33% remained progression-free at 5 years plus, without needing any further myeloma treatment during that time. And among those 33% of patients, 23% had high-risk cytogenetics, which we know are notoriously difficult to achieve responses in. What was interesting that they presented as correlative studies was there were some biomarkers that were distinguishing the patients who had the long PFS, including enrichment of more naive T-cells in the product, lower neutrophil-to-T-cell ratio, higher hemoglobin and platelets at baseline, and higher CAR T-cell levels relative to soluble BCMA levels. And the fact that they reported a median overall survival of 61 months in these really heavily pretreated patients, I think these data are impressive. I think we're going to continue to be using CAR T even earlier in the disease status than fifth or sixth line, as it was studied in CARTITUDE-1. There are even ongoing studies looking at first-line treatment with CAR T-cells. Dr. John Sweetenham: So, do you think that those 33% of patients who are disease-free at 5 years, do you think any of those are cured?  Dr. Marc Braunstein: That was one of the headlines in the press. I think if we're going to discuss things like "operational cures," where we're transforming myeloma into really a chronic disease, where patients can live practically a normal life expectancy, I think the measure of 5 years, especially in this population that was explored in CARTITUDE-1, I think we can call that close to a cure. Dr. John Sweetenham: Okay. Well, thank you. Exciting data, for sure. We're going to conclude today with another abstract in the multiple myeloma space. And this was Abstract 7500, which looked at an MRD, minimal residual disease-driven strategy following induction and transplant-eligible newly diagnosed multiple myeloma patients and reported on the primary endpoints of the phase 3 MIDAS trial. Can you walk us through this one, Marc? Dr. Marc Braunstein: Absolutely. It is a bit more complicated than the prior one we discussed because this is a randomized study with four arms. So, I'll start by saying that anti-CD38-based quadruplet regimens continue to show superior outcomes in both transplant-eligible and -ineligible newly diagnosed multiple myeloma patients. The MIDAS study mentioned is an open-label phase 3 trial with four arms in transplant-eligible newly diagnosed myeloma patients.  And initially, these patients were all treated with quadruplet therapy with the anti-CD38 antibody isatuximab combined with carfilzomib, lenalidomide, and dexamethasone in 718 newly diagnosed myeloma patients. So, they received the quadruplet regimen for six cycles and then were randomized based on their MRD status at 10 to the negative fifth following six cycles of induction. And that first randomization, if they were MRD-negative, was to either consolidation with six more cycles of the quadruplet regimen or transplant, autologous transplant, plus two cycles additionally of the quadruplet regimen. And both arms were followed by lenalidomide maintenance. The primary endpoint was MRD negativity at 10 to the negative sixth prior to entering the lenalidomide maintenance component. And in addition, the patients who were MRD-positive after induction were randomized to transplant plus two cycles of consolidation or a tandem autologous transplant. So, the median follow-up of the study was about 16 months, and the pre-maintenance rate of MRD negativity was high, between 84 to 86% between the two arms who were MRD-negative, which was not significantly different. And as far as the 233 patients who were MRD-positive, the pre-maintenance MRD negativity was also not significantly different at 40% for those who received autologous transplant, and 32% who received a tandem transplant. So, there's a lot of debate in the myeloma field about the evolving role of autologous transplant and whether transplant still plays a significant role in patients who are either MRD-negative after induction or who have deep remissions and are of standard risk. So, I think these data suggest that patients who are MRD-negative after induction with a quadruplet regimen studied here, which was Isa-KRd, plus consolidation, may possibly be able to forego consolidation with autologous transplant. And likewise, for those patients who are MRD-positive after induction, tandem transplant didn't seem to provide much of a benefit compared to single transplant, which is consistent with prior studies such as the StaMINA study. Dr. John Sweetenham: So, where do you think this leaves us, Marc? Are we going to need more studies before we have any definitive guidance on whether an autologous transplant is still appropriate for those patients who are MRD-negative? Dr. Marc Braunstein: Well, as clinicians, we want to do what's best for our patient. And in myeloma, the best we can do is to get as deep remissions as possible, meaning MRD negativity. And so, I think it's clear from the MIDAS study and others that quadruplet regimens provide the deepest remissions when given upfront. We can debate the role of autologous transplant. I think certainly the role of tandem autologous transplant is fading. But as far as a single autologous transplant as consolidation, I think it's reasonable as a goal to try to achieve MRD negativity after the transplant, especially for patients who remain MRD-positive after induction. Dr. John Sweetenham: Okay, great. Marc, thanks as always for sharing your insights on the heme malignancies studies from the ASCO meeting this year and for joining us on the ASCO Daily News Podcast. Always appreciate hearing your thoughtful and balanced input on these. Dr. Marc Braunstein: My pleasure. Thank you, John. Dr. John Sweetenham: And thank you to our listeners for joining us today. You'll find links to the abstracts discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts.   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 guest:  Dr. John Sweetenham Dr. Marc Braunstein   @docbraunstein     Follow ASCO on social media:   @ASCO on Twitter  ASCO on Bluesky  ASCO on Facebook   ASCO on LinkedIn     Disclosures:  Dr. John Sweetenham:  Consulting or Advisory Role: EMA Wellness  Dr. Marc Braunstein:  Consulting or Advisory Role: Pfizer, Bristol-Myers Squibb/Celgene, Adaptive Biotechnologies, GlaxoSmithKline, ADC Therapeutics, Janssen Oncology, Abbvie, Guidepoint Global, Epizyme, Sanofi, CTI BioPharma Corp  Speakers' Bureau: Janssen Oncology  Research Funding (Institution): Janssen, Celgene/BMS

Ruel Gaviola joins Candice to discuss 2-player abstract strategy board games with a hint of theme.00:00:00 Introduction00:01:51 LFG Con00:07:03 Ticket to Ride 20th Anniversary video 00:09:42 Fresh Plays00:09:59 Conservas00:13:16 Hot Streak00:20:15 Hits & Outs (Baseball Highlights 2045, Kaosball)00:25:44 Typeset00:30:04 Chakra00:37:44 Coloretto00:39:22 2-Player Abstract Strategy Games w/ a Hint of Theme00:44:05 Donuts00:48:08 Ironwood00:51:32 Miyabi00:54:24 Tash Kalar00:57:48 Azul01:00:44 War Chest01:04:38 Spirits of the Wild01:06:53 Toy Battle01:10:42 Samurai01:14:03 Mythic Mischief01:17:34 Santorini01:20:34 Bonus Mentions (Summoner Wars, Project L, Leaders)01:23:27 Sign-offWeb: https://boardgamegeek.com/YouTube: https://www.youtube.com/@boardgamegeekTwitter: https://twitter.com/BoardGameGeekEmail: podcast@boardgamegeek.com

Individual cells in the brain light up for specific ideas. These concept neurons, once known as “Jennifer Aniston cells,” help us think, imagine and remember episodes from our lives.

Dr. John Sweetenham and Dr. Erika Hamilton highlight key abstracts that were presented at ASCO25, including advances in breast and pancreatic cancers as well as remarkable data from the use of structured exercise programs in cancer care. Transcript Dr. Sweetenham: Hello, and welcome to the ASCO Daily News Podcast. I'm your host, Dr. John Sweetenham. Today, we'll be discussing some of the key advances and novel approaches in cancer care that were presented at the 2025 ASCO Annual Meeting. I'm delighted to be joined again by the chair of the Meeting's Scientific Program, Dr. Erika Hamilton. She is a medical oncologist and director of breast cancer and gynecologic cancer research at the Sarah Cannon Research Institute in Nashville, Tennessee.  Our full disclosures are available in the transcript of this episode. Dr. Hamilton, congratulations on a fantastic meeting. From the practice-changing science to the world-renowned speakers at this year's Meeting, ASCO25 really reflected the amazing progress we're seeing in oncology today and the enormous opportunities that lie ahead of us. And thanks for coming back on to the podcast today to discuss some of these advances. Dr. Hamilton: Thanks, Dr. Sweetenham. I'm happy to join you today. It really was an impactful ASCO Annual Meeting. I probably am biased, but some great research was presented this year, and I heard lots of great conversations happening while we were there. Dr. Sweetenham: Yeah, absolutely. There was a lot of buzz, as well as a lot of media buzz around the meeting this year, and I think that's probably a good place to start. So I'd like to dive into abstract number LBA3510. This was the CHALLENGE trial, which created a lot of buzz at the meeting and subsequently in the media. This is the study that was led by the NCI Canada Clinical Trials Group, which was the first randomized phase 3 trial in patients with stage III and high-risk stage II colon cancer, which demonstrated that a post-treatment structured exercise program is both feasible and effective in improving disease-free survival in this patient group. The study was performed over a long period of time and in many respects is quite remarkable. So, I wonder if you could give us your thoughts about this study and whether you think that this means that our futures are going to be full of structured exercise programs for those patients who may benefit. Dr. Hamilton: It's a fantastic question. I think that this abstract did create a lot of buzz. We were very excited when we read it. It was highlighted in one of the Clinical Science Symposium sessions. But briefly, this was a phase 3 randomized trial. It was conducted at 55 centers, so really a broad experience, and patients that had resected colon cancer who completed adjuvant therapy were allowed to participate. There were essentially 2 groups: a structured exercise program, called ‘the exercise group,' or health education materials alone, so that was called just ‘the health education group.' And this was a 3-year intervention, so very high quality. The primary end point, as you mentioned, was disease-free survival. This actually accrued from 2009 to 2024, so quite a lift, and almost 900 patients underwent randomization to the exercise group or the health education group. And at almost 8 years of follow-up, we saw that the disease-free survival was significantly longer in the exercise group than the health education group. This was essentially 80.3% of patients were disease-free in exercise and 73.9% in the health education group. So a difference of over 6 percentage points, which, you know, at least in the breast cancer world, we make decisions about whether to do chemotherapy or not based on these kind of data. We also looked at overall survival in the exercise group and health education group, and the 8-year overall survival was 90.3% in the exercise group and 83.2% in the health education group. So this was a difference of 7.1%. Still statistically significant. I think this was really a fantastic effort over more than a decade at over 50 institutions with almost 900 patients, really done in a very systematic, high-intervention way that showed a fantastic result. Absolutely generalizable for patients with colon cancer. We have hints in other cancers that this is beneficial, and frankly, for our patients for other comorbidities, such as cardiovascular, etc., I really think that this is an abstract that deserved the press that it received. Dr. Sweetenham: Yeah, absolutely, and it is going to be very interesting, I think, over the next 2 or 3 years to see how much impact this particular study might have on programs across the country and across the world actually, in terms of what they do in this kind of adjuvant setting for structured exercise. Dr. Hamilton: Absolutely.  So let's move on to Abstract 3006. This was an NCI-led effort comparing genomic testing using ctDNA and tissue from patients with less common cancers who were enrolled in but not eligible for a treatment arm of the NCI-MATCH trial. Tell us about your takeaways from this study. Dr. Sweetenham: Yeah, so I thought this was a really interesting study based, as you said, on NCI-MATCH. And many of the listeners will probably remember that the original NCI-MATCH study screened almost 6,000 patients to assess eligibility for those who had an actionable mutation. And it turned out that about 60% of the patients who went on to the study had less common tumors, which were defined as anything other than colon, rectum, breast, non–small cell lung cancer, or prostate cancer. And most of those patients lacked an eligible mutation of interest and so didn't get onto a trial therapy. But with a great deal of foresight, the study group had actually collected plasma samples from these patients so that they would have the opportunity to look at circulating tumor DNA profiles with the potential being that this might be another way for testing for clinically relevant mutations in some of these less common cancer types. So initially, they tested more than 2,000 patients, and to make a somewhat complicated story short, there was a subset of five histologies with a larger representation in terms of sample size. And these were cholangiocarcinoma, small cell lung cancer, esophageal cancer, pancreatic, and salivary gland cancer. And in those particular tumors, when they compared the ctDNA sequencing with the original tumor, there was a concordance there of around 84%, 85%. And in the presentation, the investigators go on to list the specific mutated genes that were identified in each of those tumors. But I think that the other compelling part of this study from my perspective was not just that concordance, which suggests that there's an opportunity there for the use of ctDNA instead of tumor biopsies in some of these situations, but what was also interesting was the fact that there were several clinically relevant mutations which were detected only in the circulating tumor DNA. And a couple of examples of those included IDH1 for cholangiocarcinoma, BRAF and p53 in several histologies, and microsatellite instability was most prevalent in small cell lung cancer in the ctDNA. So I think that what this demonstrates is that liquid biopsy is certainly a viable screening option for patients who are being assessed for matching for targeted therapies in clinical trials. The fact that some of these mutations were only seen in the ctDNA and not in the primary tumor specimen certainly suggests that there's some tumor heterogeneity. But I think that for me, the most compelling part of this study was the fact that many of these mutations were only picked up in the plasma. And so, as the authors concluded, they believe that a comprehensive gene profiling with circulating tumor DNA probably should be included as a primary screening modality in future trials of targeted therapy of this type. Dr. Hamilton: Yeah, I think that that's really interesting and mirrors a lot of data that we've been seeing. At least in breast cancer, you know, we still do a biopsy up front to make sure that our markers, we're still treating the right disease that we think we are. But it really speaks to the utility of using ctDNA for serial monitoring and the emergence of mutations. Dr. Sweetenham: Absolutely. And you mentioned breast cancer, and so I'd like to dwell on that for a moment here because obviously, there was a huge amount of exciting breast cancer data presented at the meeting this year. And in particular, I'd like to ask you about LBA1008, the DESTINY-Breast09 clinical trial, which I think has the potential to establish a new first-line standard of care for metastatic HER2+ breast cancer. And that's an area where we haven't seen a whole lot of innovation for around a decade now. So can you give us some of the highlights of this trial and what your thinking is, having seen the results? Dr. Hamilton: Yeah, absolutely. So this was a trial in the first-line metastatic HER2 setting. So this was looking at trastuzumab deruxtecan. We certainly have had no shortage of reports around this drug, initially approved for later lines. DESTINY-Breast03 brought it into our second-line setting for HER2+ disease and we're now looking at DESTINY-Breast09 in first-line. So this actually was a 3-arm trial where patients were randomized 1:1:1 against standard taxane/trastuzumab/pertuzumab in one arm; trastuzumab deruxtecan with pertuzumab in another arm; and then a third arm, trastuzumab deruxtecan alone. And what we did not see reported was that trastuzumab deruxtecan-alone arm. But we did have reports from the trastuzumab deruxtecan plus pertuzumab versus the chemo/trastuzumab/pertuzumab. And what we saw was a statistically significant improvement in median progression-free survival, 26.9 months up to 40.7, so an improvement of 13.8 months, over a year in PFS. Not to mention that we're now in the 40-month range for PFS in first-line disease. Really, across all subgroups, we really weren't able to pick out a subset of patients that did not benefit. We did see about a 12% ILD rate with trastuzumab deruxtecan. That really is on par with what we've seen in other studies, around 10%-15%. I think that this is going to become a new standard of care in the first-line. I think it did leave some unanswered questions. We saw some data from the PATINA trial this past San Antonio Breast, looking at the addition of endocrine therapy with or without a CDK4/6 inhibitor, palbociclib, for those patients that also have ER+ disease, after taxane has dropped out in the first-line setting. So how we're going to kind of merge all this together is, I suspect that there are going to be patients that we or they just don't have the appetite to continue 3 to 4 years of trastuzumab deruxtecan. And so we're probably going to be looking at a maintenance-type strategy for them, maybe integrating the PATINA data there. But how we really put this into practice in the first-line setting and if or when we think about de-escalating down from trastuzumab deruxtecan to antibody therapy are some lingering questions. Dr. Sweetenham: Okay, so certainly is going to influence practice, but watch this space for a little bit longer, it sounds as though that's what you're saying. Dr. Hamilton: Absolutely.  So let's move on to GI cancer. Abstract 4006 reported preliminary results from the randomized phase 2 study of elraglusib in combination with gemcitabine/nab-paclitaxel versus the chemo gemcitabine/nab-paclitaxel alone in patients with previously untreated metastatic pancreatic cancer. Can you tell us more about this study? Dr. Sweetenham: Yeah, absolutely. As you mentioned, elraglusib is actually a first-in-class inhibitor of GSK3-beta, which has multiple potential actions in pancreatic cancer. But the drug itself may be involved in mediating drug resistance as well as in some tumor immune response modulation. Some of that's not clearly understood, I believe, right now. But certainly, preclinical data suggests that the drug may be effective in preclinical models and may also be effective in combination with chemotherapy and potentially with immune-modulating agents as well. So this particular study, as you said, was an open-label, randomized phase 2 study in which patients with pancreatic cancer were randomized 2:1 in favor of the elraglusib plus GMP—gemcitabine and nab-paclitaxel—versus the chemotherapy alone. And upon completion of the study, which is not right now, median overall survival was the primary end point, but there are a number of other end points which I'll talk about in just a moment. But the sample size was planned to be around 207 patients. The primary analysis included 155 patients in the combination arm versus 78 patients in the gemcitabine/nab-paclitaxel arm. Overall, the 1-year overall survival rate was 44.1% for the patients in the elraglusib-containing arm versus 23.0% in the patients receiving gemcitabine/nab-paclitaxel only. When they look at the median overall survival, it was 9.3 months for the experimental arm versus 7.2 months for chemotherapy alone. So put another way, there's around a 37% reduction in the risk of death with the use of this combination arm. The treatment was overall well-tolerated. There were some issues with grade 1 to 2 transient visual impairment in a large proportion of the patients. The most common treatment-related adverse effects with the elraglusib/GMP combination was transient visual impairment, which affected around 60% of the patients. Most of the more serious treatment-related adverse events included neutropenia, anemia, and fatigue in 50%, 25%, and 16% of the patients, respectively. So the early results from this study show a significant benefit for 1-year overall survival and for median overall survival with, as I mentioned above, a significant reduction in the risk of death. The authors went on to mention that the median overall survival for the control arm in this study is somewhat lower than in other comparable trials, but they think that this may be related to a more advanced disease burden in this particular study. Of interest to me was that right now: there is no apparent difference in progression-free survival between the 2 arms of this study. The authors described this as potentially indicating that this may be related in some way to immune modulation and immune effects on the tumor, which, if I'm completely honest, I don't totally understand. And so, the improvement in overall survival, as far as I can see at the moment, is not matched by an improvement in progression-free survival. So I think we probably need to wait for more time to elapse to see what happens with the study. And so, I think it certainly is an interesting study, and the results are intriguing, but I think it's probably a little early for it to actually shift the treatment paradigm in this disease. Dr. Hamilton: Fantastic. I think we've been waiting for advances in pancreatic cancer for a long time, but this, not unlike others, we learn more and then learn more we don't realize, so. Dr. Sweetenham: Right. Let's shift gears at this point and talk about a couple of other abstracts in kind of a very different space. Let's start out with symptom management for older adults with cancer. We know that undertreated symptoms are common among the older patient population, and Abstract 11002 reported on a randomized trial that demonstrated the effects of remote monitoring for older patients with cancer in terms of kind of symptoms and so on. Can you tell us a little bit about this study and whether you think this approach will potentially improve care for older patients? Dr. Hamilton: Yeah, I really liked this abstract. It was conducted through the Veterans Affairs, and it was based in California, which I'm telling you that because it's going to have a little bit of an implication later on. But essentially, adults that were 75 years or older who were Medicare Advantage beneficiaries were eligible to participate. Forty-three clinics in Southern California and Arizona, and patients were randomized either into a control group of usual clinic care alone, or an intervention group, which was usual care plus a lay health worker-led proactive telephone-based weekly symptom assessment, and this was for 12 months using the validated Edmonton Symptom Assessment System. So, there was a planned enrollment of at least 200 patients in each group. They successfully met that. And this lay health worker reviewed assessments with a physician assistant, who conducted follow-up for symptoms that changed by 2 points from a prior assessment or were rated 4 or greater. So almost a triage system to figure out who needed to be reached out to and to kind of work on symptoms. What I thought was fantastic about this was it was very representative of where it enrolled. There were actually about 50% of patients enrolled here that were Hispanic or Latinos. So some of our underserved populations and really across a wide variety of tumor types. They found that the intervention group had 53% lower odds of emergency room use, 68% lower odds of hospital use than the control group. And when they translated this to actual total cost of care, this was a savings of about $12,000 U.S. per participant and 75% lower odds of a death in an acute care facility. So I thought this was really interesting for a variety of reasons. One, certainly health care utilization and cost, but even more so, I think any of our patients would want to prevent hospitalizations and ER visits. Normally, that's not a fantastic experience having to feel poorly enough that you're in the emergency room or the hospital. And really showing in kind of concrete metrics that we were able to decrease this with this intervention. In terms of sustainability and scalability, I think the question is really the workforce to do this. Obviously, you know, this is going to take dedicated employees to have the ability to reach out to these patients, etc., but I think in value-based care, there's definitely a possibility of having reimbursement and having the funds to institute a program like this. So, definitely thought-provoking, and I hope it leads to more interventions. Dr. Sweetenham: Yeah, we've seen, over several years now, many of these studies which have looked at remote symptom monitoring and so on in this patient population, and many of them do show benefits for that in kinds of end points, not the least in this study being hospitalization and emergency room avoidance. But I think the scalability and personnel issue is a huge one, and I do wonder at some level whether we may see some AI-based platforms coming along that could actually help with this and provide interactions with these patients outside of actual real people, or at least in combination with real people. Dr. Hamilton: Yeah, that's a fantastic point.  So let's talk a little bit about clinical trials. So eligibility assessment for oncology clinical trials, or prescreening, really relies on manual review of unstructured clinical notes. It's time-consuming, it's prone to errors, and Abstract 1508 reported on the final analysis of a randomized trial that looked at the effect of human-AI teams prescreening for clinical trial eligibility versus human-only or AI-only prescreening. So give us more good news about AI. What did the study find? Dr. Sweetenham: Yeah, this is a really, a really interesting study. And of course, any of us who have ever been involved in clinical trials will know that accrual is always a problem. And I think most centers have attempted, and some quite successfully managed to develop prescreening programs so that patients are screened by a health care provider or health care worker prior to being seen in the clinic, and the clinical investigator will then already know whether they're going to be eligible for a trial or not. But as you've already said, it's a slow process. It's typically somewhat inefficient and requires a lot of time on the part of the health care workers to actually do this in a successful way. And so, this was a study from Emory University where they took three models of ways in which they could assess the accuracy of the prescreening of charts for patients who are going to be considered for clinical trials. One of these was essentially the regular way of having two research coordinators physically abstract the charts. The second one was an AI platform which would extract longitudinal EHR data. And then the third one was a combination of the two. So the AI would be augmented by the research coordinator or the other way around. As a gold standard, they had three independent oncology reviewers who went through all of these charts to provide what they regarded as being the benchmark for accuracy. In a way, it's not a surprise to me because I think that a number of other systems which have used this combination of human verification of AI-based tools, it actually ultimately concluded that the combination of the two in terms of chart accuracy was for the most part better than either one individually, either the research coordinator or the AI alone. So I'll give you just a few examples of where specifically that mattered. The human plus AI platform was more accurate in terms of tumor staging, in terms of identifying biomarker testing and biomarker results, as well as biomarker interpretation, and was also superior in terms of listing medications. There are one or two other areas where either the AI alone was somewhat more accurate, but the significant differences were very much in favor of a combination of human + AI screening of these patient charts. So, in full disclosure, this didn't save time, but what the authors reported was that there were definite efficiency gains, and presumably this would actually become even more improved once the research coordinators were somewhat more comfortable and at home with the AI tool. So, I thought it was an interesting way of trying to enhance clinical trial accrual up front by this combination of humans and technology, and I think it's going to be interesting to see if this gets adopted at other centers in the future. Dr. Hamilton: Yeah, I think it's really fascinating, all the different places that we can be using AI, and I love the takeaway that AI and humans together are better than either individually. Dr. Sweetenham: Absolutely.  Thanks once again, Dr. Hamilton, for sharing your insights with us today and for all of the incredible work you did to build a robust program. And also, congratulations on what was, I think, a really remarkable ASCO this year, one of the most exciting for some time, I think. So thank you again for that. Dr. Hamilton: Thanks so much. It was really a pleasure to work on ASCO 2025 this year. Dr. Sweetenham: And thank you to our listeners for joining us today. You'll find links to all the abstracts we discussed today in the transcript of this episode. Be sure to catch up on all of our coverage from the Annual Meeting. You can catch up on my daily reports that were published each day of the Annual Meeting, featuring the key science and innovations presented. And we'll have wrap-up episodes publishing in June, covering the full spectrum of malignancies from ASCO25. If you value the insights you hear on the ASCO Daily News Podcast, please remember to rate, review, and subscribe wherever you get your podcasts. 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.   More on today's speakers: Dr. John Sweetenham   Dr. Erika Hamilton @erikahamilton9   Follow ASCO on social media:  @ASCO on Twitter  ASCO on Bluesky  ASCO on Facebook   ASCO on LinkedIn     Disclosures:     Dr. John Sweetenham:     No relationships to disclose    Dr. Erika Hamilton: Consulting or Advisory Role (Inst): Pfizer, Genentech/Roche, Lilly, Daiichi Sankyo, Mersana, AstraZeneca, Novartis, Ellipses Pharma, Olema Pharmaceuticals, Stemline Therapeutics, Tubulis, Verascity Science, Theratechnologies, Accutar Biotechnology, Entos, Fosun Pharma, Gilead Sciences, Jazz Pharmaceuticals, Medical Pharma Services, Hosun Pharma, Zentalis Pharmaceuticals, Jefferies, Tempus Labs, Arvinas, Circle Pharma, Janssen, Johnson and Johnson   Research Funding (Inst): AstraZeneca, Hutchison MediPharma, OncoMed, MedImmune, Stem CentRx, Genentech/Roche, Curis, Verastem, Zymeworks, Syndax, Lycera, Rgenix, Novartis, Millenium, TapImmune, Inc., Lilly, Pfizer, Lilly, Pfizer, Tesaro, Boehringer Ingelheim, H3 Biomedicine, Radius Health, Acerta Pharma, Macrogenics, Abbvie, Immunomedics, Fujifilm, eFFECTOR Therapeutics, Merus, Nucana, Regeneron, Leap Therapeutics, Taiho Pharmaceuticals, EMD Serono, Daiichi Sankyo, ArQule, Syros Pharmaceuticals, Clovis Oncology, CytomX Therapeutics, InventisBio, Deciphera, Sermonix Pharmaceuticals, Zenith Epigentics, Arvinas, Harpoon, Black Diamond, Orinove, Molecular Templates, Seattle Genetics, Compugen, GI Therapeutics, Karyopharm Therapeutics, Dana-Farber Cancer Hospital, Shattuck Labs, PharmaMar, Olema Pharmaceuticals, Immunogen, Plexxikon, Amgen, Akesobio Australia, ADC Therapeutics, AtlasMedx, Aravive, Ellipses Pharma, Incyte, MabSpace Biosciences, ORIC Pharmaceuticals, Pieris Pharmaceuticals, Pieris Pharmaceuticals, Pionyr, Repetoire Immune Medicines, Treadwell Therapeutics, Accutar Biotech, Artios, Bliss Biopharmaceutical, Cascadian Therapeutics, Dantari, Duality Biologics, Elucida Oncology, Infinity Pharmaceuticals, Relay Therapeutics, Tolmar, Torque, BeiGene, Context Therapeutics, K-Group Beta, Kind Pharmaceuticals, Loxo Oncology, Oncothyreon, Orum Therapeutics, Prelude Therapeutics, Profound Bio, Cullinan Oncology, Bristol-Myers Squib, Eisai, Fochon Pharmaceuticals, Gilead Sciences, Inspirna, Myriad Genetics, Silverback Therapeutics, Stemline Therapeutics

We talked about older games last week - this week we're moving on to modern abstract games (within the last 20 years). The post Episode 399 – Room to Grow: Modern Abstract Games appeared first on The Family Gamers.

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Notice that the more attention is in abstraction, the harder things feel. More abstract, more problems. Really, all problems are abstractions. You can't find a problem outside of abstraction.Me-and-my-life is the ultimate abstraction. When we live with attention there, as we so often do, life feels extremely hard. Even when it's good, it's not that The post EP357: More abstract, more suffering appeared first on Dr. Amy Johnson.

Episode 5 of Ways of Knowing -- Season 2, an audio series about the humanities. Made by The World According to Sound and The University of Washington. This episode features the work of professor of Math and the Comparative History of Ideas, Jayadev Athreya.

This week is devoted to older, classic abstract games. You probably know how to play these timeless games already, and have some of them relegated to the back corner of your shelves or your closet. The post Episode 398 – Room to Grow: Classic Abstract Games appeared first on The Family Gamers.

Let's practice some common Spanish abstract nouns, including nombre, tipo, historia, and poco. Practice all of today's Spanish for free at LCSPodcast.com/74