POPULARITY
9 episodes with MUC
6 episodes with MUC
5 episodes with MUC
3 episodes with MUC
4 episodes with MUC
2 episodes with MUC
2 episodes with MUC
4 episodes with MUC
2 episodes with MUC
This week the MotoXpod will feature Muc-off/FXR/ClubMX Yamaha's Coty Schock, Team Green's Aden Keefer, and Altus/BLUCRU/Yamaha's Lachlan Turner. Let us know your thoughts below. If you have any questions for the guests let us know. You can also email Motoxpodshow@Gmail.com if you want to get in on the Evan's Coolant Emails, T-Bolt USA Top 5, FXR picks for High Point, and the X Brand Forum Check-In. Watch live on the Vital MX YouTube channel starting at 4:30 Pacific/7:30 Eastern.
Stāsta Latvijas Universitātes Akadēmiskās bibliotēkas Rokrakstu un reto grāmatu nodaļas vadītāja, vadošā pētniece Aija Taimiņa. Siļķes, šaujampulveris, medus, skābēti kāposti, vīns, alus, eļļa, labība, tauki, ogles, degvīns un viskijs, un apelsīni, un grāmatas… Vai varat atminēt, kas vieno visu uzskaitīto (un vēl arī nepieminēto)? Ja tirgus precei ilgi jāglabājas un jādodas tālā ceļā, bez piemērota un droša iepakojuma neiztikt. Ozola muca gadsimtiem ilgi ir kalpojusi kravu transportam – pa ūdensceļiem pārvietojās mucām piekrautas liellaivas un kuģi, pa zemesceļiem preci mucās veda smago ormaņu pajūgi. Muca ir sen zināms, standartizēts svara un tilpuma mērs, tās lielumu un formu noteica uzglabājamā produkta veids. Dažādas mucas apraksta seni vēstures avoti. Mucā varēja pārlaist naktis, pat dzīvot, kā vēsta leģenda par antīko grieķu filosofu kiniķi Diogenu un imperatoru Aleksandru Lielo. Tiesa, Diogēna muca (dolia), visdrīzāk, bija darināta no māla. Jūlijs Cēzars licis ar katapultām mest degošas mucas aplenktajās pilsētas, lai izraisītu ugunsgrēkus, savukārt Marseļas aizstāvji laiduši virsū degošas mucas aplencējiem. Alpos, gallu ciemos redzētās triju veidu koka dēlīšu mucas pirmais aprakstījis romiešu dabaszinātnieks Plīnijs Vecākais. Viduslaikos mucenieku amata meistari prata izgatavot dažāda veida mucas lielā skaitā, turklāt katru mucu meistars marķēja ar savu zīmi, tā garantējot sava darba kvalitāti. Rīgā mucu meistaru pienākumus un mucinieku amata jeb kompānijas (cumpanye van deme bodekwerke) kārtību jau kopš 1375. gada noteica šrāga (der bodeker schra). Rīgas meistariem bija jāprot izgatavot triju lielumu mucas. Mucu izmantošana grāmatu, pergamenta rokrakstu un dokumentu ruļļu transportam ir mazāk zināms, mūsdienās pat mulsinošs grāmattirdzniecības vēstures jautājums. Līdz ar grāmatu iespiešanas sākotni (Mainca, 1450) Eiropā spēji palielinājās iespiesto grāmatu kopskaits, tika dibinātas jaunas tipogrāfijas un atvērti jauni grāmatu veikali un izdevniecību pārstāvniecības. Pirmajos 50 grāmatiespiešanas gados Eiropā tika izveidotas 282 tipogrāfijas, kurās iespieda aptuveni 29 000 izdevumus, katru no tiem iespieda daudzos (100–300) eksemplāros. Eiropu pārpludināja aptuveni pusmiljons (550 000) iespiestu grāmatu; tās pirka un pārdeva, grāmatu tirdzniecības apgrozījums pieauga daudzkārt. Grāmatas tirgoja veikalos, grāmatsietuvēs un pilsētu gadatirgos. Frankfurtes grāmatu gadatirgus (Buchmesse) ir visvecākais un slavenākais grāmatu gadatirgus jau 500 gadus. Dažāda lieluma, bieži samērā smagu grāmatu pārvietošana bija visai nopietns jautājums. Grāmatu papīrs vai pergaments ceļojuma laikā nedrīkstēja ciest – aizvākota, noblīvēta muca labi sargāja no mitruma un cita veida bojājumiem. Ar grāmatu pārdošanu un transportēšanu no un uz gadatirgiem nodarbojās īpaši specializējušies pārvadātāji–grāmatu tirgotāji jeb ceļojošie grāmatu vedēji (Buchführer). No drukas kungiem (proti, tipogrāfiem) saņemtās grāmatas varēja pārvietot saiņos (Ballen), kastēs un mucās, iepakoto preci nodeva pārvadātāju (smago ormaņu vai kuģinieku) rīcībā, turklāt pēc saņemšanas iztukšotā grāmatu muca bija jāatgriež tirgotājam. Grāmatu tirgotāji redzami vien pāris 16. un 17. gs. attēlos. Zīmējums Nirnbergas amatnieku brālības piemiņas grāmatā (att.) rāda vietējo grāmatu vedēju Hansu Kepneru (Keppner, +1543), kas septiņus gadus darbojies amatā. Kepners liek vidēja lieluma grāmatas visai augstā, stīpotā mucā. Cits attēls liecina, ka grāmatu muca varēja būt zema un plata. Tādu mucu grāmatu tirgotāju veikala noliktavā 1698. gadā redzējis vācu gravieris Kristofs Veigels (Weigel), kurš attēloto ainu pavadījis ar pamācošu, pārdomu pilnu dzejolīti: "Grāmatu tirgotājs ved jums gudrības dārgumus, atrodiet vietu labām grāmatām. Kas gan še ir cilvēka miesa? / Ceļinieka manta zūdīga, visos laikos, / blīvi apdrukāts papīrs, / grāmata, rūpestos iesieta; ar to tirgojas nāve un laiks, / līdz beidzot mūžība izpako." Abi attēli liecina, ka mucās blīvi pakotas jau iesietas grāmatas. Nirnbergas grāmatu vedējs kārto mucā atbilstoši vācu renesanses gaumei iesietas grāmatas ar melnu un sarkanu ādu pārvilktos koka vākos ar slēdžiem un apkalumiem. Tomēr jāzina, ka grāmatu vedēji un tirgotāji parasti transportēja neiesietas grāmatas, pircējs pats pēc savas gaumes un rocības pasūtīja un apmaksāja iesiešanu. Tāpēc mūsu bibliotēku krājumos atrodamas daudzas 15.–16. gs. Venēcijā vai Nirnbergā drukātas grāmatas, kuru iesējumi visdrīzāk darināti Rīgā. Tas arī saprotams, jo smagie koka vāki grāmatu mucas svaru stipri palielināja, bet muitas un tirgus nodevas bija atkarīgas no preces svara. Nav šaubu, ka ārzemju grāmatu tirgotāji 15.–17. gs. pārdeva savu preci Rīgas gadatirgos, bet Rīgas pirmais grāmatiespiedējs Nikolauss Mollīns 1599. gadā veda savus izdevumus uz Frankfurtes gadatirgu. Lai gan droši tas nav zināms, var pieņemt, ka pa laikam šīs grāmatas tika pārvietotas mucās. Laba, liela muca ir visādi noderīga. Muca glābj nelaikā pārsteigtus mīlniekus: Džovanni Bokačo “Dekamerona” (1348) 7. dienas novele stāsta, kā liela muca ļāva izmanīgai neapolietei apmānīt savu vīru un ļauties mīlas priekiem ar mīļāko. Mucā var paslēpties kopā ar savu “klarineti”, lai noklausītos citu runas. Uz mucas var pakāpties, lai dziedātu vakara dziesmu iemīļotajai, kā to gribēja precēties kārais Dundurnieks Ādolfa Alunāna dziesmu spēlē “Mucenieks un muceniece” (1872). Un tā vien šķiet, ka asprātīgais latviešu teātra tēvs Alunāns vēlējies parādīt, ka viņam viduslaiku erotiskais stāsts par mucu ir zināms. No amatniekiem visiem ir Tas jautrāks mucenieks, Pie darba citi sten un pūš, Bet mūsu darbs ir prieks. (Ādolfs Alunāns. Mucenieks un muceniece)
Jeannie Hoffman-Censits discusses her randomized phase 2 adding SG to maintenence avelumab in mUC.
Muc tiêu cấp sổ hồng điện tử được dư luận quan tâm bởi đánh dấu sự thay đổi phương thức quản lý, giúp bảo đảm minh bạch và phục vụ người dân tốt hơn. Quy trình cấp sổ hồng điện tử sẽ diễn ra như thế nào và sử dụng sổ điện tử ra sao?
Vernissage „AST & AST“ mit Alix Stadtbäumer und Angela Stauber - Galerie PingRodach(Hördauer 57 Minuten)Der Frühling ist da – zart und doch unübersehbar. In dieser Atmosphäre, in der Licht, Farbe und Stille neu ineinandergreifen, öffnet sich in der Galerie PINGRODACH eine Ausstellung, die dem Moment entspricht: „AST & AST“ vereint Arbeiten von Angela Stauber und Alix Stadtbäumer und lädt uns ein zur stillen Betrachtung und zur Entdeckung vielschichtiger Verbindungen.Beide Künstlerinnen wurden in diesem Jahr mit dem renommierten Stipendium der Stiftung Kunstfonds 2025 ausgezeichnet – ein Zeichen für die besondere Qualität ihrer Arbeit und ein schöner Moment, um diesen künstlerischen „Zweig“ gemeinsam wachsen zu lassen.Alix Stadtbäumer entwickelt skulpturale Arbeiten, die sich zwischen Bildhauerei, Rauminstallation und Kunst am Bau entfalten. – alltägliche Formen werden transformiert, neu lesbar, neu erlebbar.Angela Stauber hingegen malt mit einem außergewöhnlich feinen Sensorium für Licht, Stille und Wahrnehmung.Im Verlauf der Sendung werde ich nicht nur die beiden Künstlerinnen, sondern auch den Kurator Johannes Rodach seine neue Mitarbeiterin und einige Besucherinnen und Besucher zu Wort kommen lassen. Ich lade sie ein, uns einige der ausgestellten Bilder und Skulpturen zu beschreiben – damit wir den Zuhörenden vor allem auch den sehbehinderten und blinden Menschen, über unser Radio, einen Eindruck von dieser wunderbaren und interessanten Ausstellung vermitteln können.Freuen Sie sich auf persönliche Gespräche, spannende Einblicke in die künstlerischen Prozesse und auf einen konzentrierten, inspirierenden Abend mit „AST & AST“.
Send us a textUnter dem Motto „Find me if you can“ versteckt Uptrip vom 20. April bis 20. Mai ganz besondere NFT-Sammelkarten an ausgewählten Flughäfen in Deutschland und Österreich – mit starken Preisen für Miles & More-Teilnehmende und Uptrip-Nutzer:innen:
In this episode we are joined again by Muc Simons. Muc has had one heck of a fall so far and tells the story of his monster Mule Deer as well as his successful antelope hunt which was 30 years in the making. We get into some CWD talk and Derek shares the story of his sons epic elk hunt, which you are sure to pull some great tips away from. For more on Muc go to.... https://www.facebook.com/marcus.simons https://www.youtube.com/@muc100 Instagram https://akuoutdoor.ca/ Use Promo code FOCUS for 15% off Hunting & Military Boots https://akuoutdoor.us/ Use Promo code FOCUS for 15% off Hunting & Military Boots https://www.treelineacademy.net/ use promo code "FOCUS22" and get $20USD off the course This episode of the Focus Hunting Podcast is brought to you by: Hard Core Archery Howl For Wildlife Learn more about your ad choices. Visit megaphone.fm/adchoices
Like what you hear? Show some love and send a text. #Cheers In this episode, we dive into the chaotic, hilarious, and action-packed world of Deadpool! Join Reels, Booze & Bro's aka RB2podcast as we explore the unconventional origin story of Wade Wilson, portrayed by the ever-charming Ryan Reynolds. From his days as a wisecracking mercenary to his transformation into the unkillable antihero we all love, we'll cover it all. Support the Show.
Heute sprechen Masha und Claus mit Denise - sie ist Apron Controllerin am Flughafen München. Sie nimmt uns mit in Ihren Tower am Vorfeld in MUC - dort ist sie die Koordinatorin über alle Flugbewegungen am Boden. Wenn Ihr mehr erfahren wollt über diesen sehr coolen und spannenden Beruf - und wie Denise aus Berlin-Kreuzberg vor über zwanzig Jahren über Wien und Frankfurt nach München gekommen ist - hier erfahrt Ihr es.
When the mucin-1 (MUC-1) vaccine tecemotide was added to standard-of-care neoadjuvant systemic therapy, investigators in Austria found improved long-term outcomes in women with early breast cancer. Individuals vaccinated with tecemotide had markedly longer distant recurrence-free and overall survival. This was in the randomized prospective ABCSG-34 trial presented at the 2024 ASCO Annual Meeting. Oncology Times reporter Peter Goodwin met up in Chicago with the lead study author, Christian F. Singer MD, a gynecologist specializing in breast cancer at the Department of Obstetrics and Gynecology and the Comprehensive Cancer Center of the Medical University of Vienna, in Vienna, Austria.
On this episode the guys chat with Muc Simmons and Landen Fidek. Landen and Muc are both experienced hunters and some of the best when it comes to targeting big mature boars. With nearly 2 decades of hunting mature black bears between them they have proven success year after year when it comes to harvesting big bears in Manitoba. Kevin joined the pair recently for a second trip to hunt bears in Manitoba and it did not disappoint. The guys recap their amazing trip which ended in Landen taking a massive 480 pound color phase bear they named Vico. Kevin, Much and Landen share the details of this amazing adventure. For more on Muc and Landen go to... Muc Simons (@muc_simons) • Instagram photos and videos Landen Fidek (@lfidek) • Instagram photos and videos As always be sure to check out our sponsors and use the promo codes... http://lab.mtntough.com/checkout/subscribe/purchase?code=fhp30&plan=monthly Use Code FHP30 https://akuoutdoor.ca/ Use Promo code FOCUS for 15% off Hunting & Military Boots https://akuoutdoor.us/ Use Promo code FOCUS for 15% off Hunting & Military Boots https://www.treelineacademy.net/ use promo code "FOCUS22" and get $20USD off the course This episode of the Focus Hunting Podcast is brought to you by: Hard Core Archery Howl For Wildlife Learn more about your ad choices. Visit megaphone.fm/adchoices
Today we're taking a look at the possibility of Agents of Atlas joining the MUC. The MCU has been pretty hit or miss for most. Can this be what saves the MCU or will it be the final straw that send fans over to the DC side of cinema?
This is a replay of episode #118 we did over 1 year ago. This was such an outstanding episode we decided to replay the entire episode. Muc talks about his four-year pursuit of a monster bear he named Warpig. This hunt was four years in the making and after many close encounters and heartache Muc was finally able to connect. Muc shares his baiting setups and talks about his stands. Great information for those who are able to bait spring black bears. For more on Muc go to... https://www.instagram.com/muc_simons/ https://www.youtube.com/@muc100/videos https://www.facebook.com/AlloutdoorswithMuc/ As always be sure to check out our sponsors and use the promo codes... http://lab.mtntough.com/checkout/subscribe/purchase?code=fhp30&plan=monthly Use Code FHP30 https://akuoutdoor.ca/ Use Promo code FOCUS for 15% off Hunting & Military Boots https://akuoutdoor.us/ Use Promo code FOCUS for 15% off Hunting & Military Boots https://www.treelineacademy.net/ use promo code "FOCUS22" and get $20USD off the course This episode of the Focus Hunting Podcast is brought to you by: Hard Core Archery Howl For Wildlife Learn more about your ad choices. Visit megaphone.fm/adchoices
On this episode we are joined by friend and experienced bear hunter, Muc Simmons. The guys get talk archery, spring bear and early bear habits. Kevin and Muc chat about their Manitoba Bear hunt planned in May. For more on Muc go to.... https://www.instagram.com/muc_simons/ https://www.youtube.com/@muc100/videos https://www.facebook.com/AlloutdoorswithMuc/ As always be sure to check out our sponsors and use the promo codes... http://lab.mtntough.com/checkout/subscribe/purchase?code=fhp30&plan=monthly Use Code FHP30 https://akuoutdoor.ca/ Use Promo code FOCUS for 15% off Hunting & Military Boots https://akuoutdoor.us/ Use Promo code FOCUS for 15% off Hunting & Military Boots https://www.treelineacademy.net/ use promo code "FOCUS22" and get $20USD off the course This episode of the Focus Hunting Podcast is brought to you by: Hard Core Archery Howl For Wildlife Learn more about your ad choices. Visit megaphone.fm/adchoices
Unfortunately Johnny couldn't be with us tonight as he had to take shelter from tornados and crazy hail storms rolling through central Ohio. I go over Camille's epic 6 days at the Lululemon event in La Quinta, CA where she broke a bunch of world records including the 6 day record. Ashley Paulson's magical year keeps rolling as she gets another 100 mile victory. I talk about my experience at MUC 50 on Saturday and go over some other race results. I break down an article about statistical correlations on why runners DNF and also one about the longest run on record in Antarctica! Run (Outside) article about the 6 day lululemon event: https://run.outsideonline.com/road/inside-further-an-ultra-for-the-instagram-age/ Guardian article about Camille and the 6 day lululemon event: https://www.theguardian.com/sport/2024/mar/13/naps-tacos-and-11-world-records-how-camille-herron-ran-560-miles-in-six-days?fbclid=IwAR3oY4VFNI83U59-jT_9oqj_MffhRPVPgb11bL7qakqVhwD29mLSk3uaHrM Irunfar article on DNFs: https://www.irunfar.com/diving-into-ultramarathon-dnf-data Longest run in Antarctica: https://www.ctvnews.ca/sports/she-battled-sub-zero-temperatures-and-ferocious-winds-to-record-the-longest-ever-run-in-antarctica-1.6800861 Socials Instagram: https://www.instagram.com/ultrarunning_news_network/ Facebook: https://www.facebook.com/profile.php?id=61555338668719 X (Twitter): https://twitter.com/ultrarunnews Threads: https://www.threads.net/@ultrarunning_news_network Email: ultrarunning.news.network@gmail.com
BUFFALO, NY- March 4, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on February 22, 2024, entitled, “Sacituzumab govitecan plus platinum-based chemotherapy mediates significant antitumor effects in triple-negative breast, urinary bladder, and small-cell lung carcinomas.” Sacituzumab govitecan (SG) is an antibody-drug conjugate composed of an anti-Trop-2-directed antibody conjugated with the topoisomerase I inhibitory drug, SN-38, via a proprietary hydrolysable linker. SG has received United States Food and Drug Administration (FDA) approval to treat metastatic triple-negative breast cancer (TNBC), unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, and accelerated approval for metastatic urothelial cancer (mUC). In this new study, researchers Thomas M. Cardillo, Maria B. Zalath, Roberto Arrojo, Robert M. Sharkey, Serengulam V. Govindan, Chien-Hsing Chang, and David M. Goldenberg from Gilead Sciences and the Center for Molecular Medicine and Immunology investigated the utility of combining SG with platinum-based chemotherapeutics in TNBC, urinary bladder carcinoma (UBC), and small-cell lung carcinoma (SCLC). “Given recent FDA approval of SG in mTNBC and accelerated approval in mUC [metastatic urothelial cancer], as well as its demonstrated clinical activity in SCLC [11], we investigated the possibility of expanding use of SG through combinations with currently utilized chemotherapeutics for these disease indications.” SG plus carboplatin or cisplatin produced additive growth-inhibitory effects in vitro that trended towards synergy. Immunoblot analysis of cell lysates suggests perturbation of the cell-cycle and a shift towards pro-apoptotic signaling evidenced by an increased Bax to Bcl-2 ratio and down-regulation of two anti-apoptotic proteins, Mcl-1 and survivin. Significant antitumor effects were observed with SG plus carboplatin in mice bearing TNBC or SCLC tumors compared to all controls (P < 0.0062 and P < 0.0017, respectively) and with SG plus cisplatin in UBC and SCLC tumor-bearing animals (P < 0.0362 and P < 0.0001, respectively). These combinations were well tolerated by the animals. “Combining SG with platinum-based chemotherapeutics demonstrates the benefit in these indications and warrants further clinical investigation.” DOI - https://doi.org/10.18632/oncotarget.28559 Correspondence to - Thomas M. Cardillo - Thomas.Cardillo1@Gilead.com Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28559 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, sacituzumab govitecan, Trop-2, SN-38, carboplatin, cisplatin About Oncotarget Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957
Drew is in Hong Kong, with return guest Ian, while Doug is in North Carolina for KC46 training. Ian and Drew are fresh off flights from LAX where they met up with avgeek friends. We discuss:Lara of Nonrev Lounge has her birthday at LAX…of courseGetting from LAX to HKG via MUC and ZRH? It's complicated4 engines for long haul. We discuss the A340737 Max update Lufthansa ground workers strikeMaybe they're Vince Peterson stairs, not DB Cooper?What's KLM Asia?Join the conversation! https://www.nexttripnetwork.com/
This week on BackTable Urology, urologic oncologist Dr. Bogdana Schmidt (University of Utah) hosts a discussion with medical oncology experts Dr. Rana McKay (UC San Diego) and Dr. Neeraj Agarwal (University of Utah) on recent clinical trials from bladder, kidney, and prostate cancer research presented at the 2023 European Society for Medical Oncology (ESMO) Meeting. First, they discuss impactful data regarding bladder cancers, specifically the CheckMate 901 and the EV-302 trials which show improvement in overall survival and promise for urothelial carcinoma patients' quality of life. The conversation moves onto kidney-specific trials such as the LITESPARK-005, which offers improved progression-free survival for patients through the use of belzutifan. The panel rounds off by discussing the progress made in prostate-specific trials with emphasis on the EMBARK and SPLASH trials involving Lutetium therapy. Finally, the doctors discuss the trend towards personalized treatment plans based on the unique goals and health requirements of the patients. --- SHOW NOTES 00:00 - Discussion on Urothelial Carcinoma: CheckMate 901 and EV-302 11:22 - Discussion on Kidney Cancer: LITESPARK-005 23:53 - Discussion on Prostate Cancer: EMBARK 31:41 - Discussion on Prostate Cancer: SPLASH vs PSMA 36:39 - Future Directions for Lutetium Therapy for Prostate Cancer 37:50 - Closing Remarks and Future Expectations --- RESOURCES CheckMate 901 Trial Investigators. Nivolumab plus Gemcitabine-Cisplatin in Advanced Urothelial Carcinoma. https://www.nejm.org/doi/full/10.1056/NEJMoa2309863 LBA6 EV-302/KEYNOTE-A39: Open-label, randomized phase III study of enfortumab vedotin in combination with pembrolizumab (EV+P) vs chemotherapy (Chemo) in previously untreated locally advanced metastatic urothelial carcinoma (la/mUC). https://www.sciencedirect.com/science/article/pii/S0923753423042709 LBA88 Belzutifan versus everolimus in participants (pts) with previously treated advanced clear cell renal cell carcinoma (ccRCC): Randomized open-label phase III LITESPARK-005 study. https://www.sciencedirect.com/science/article/pii/S0923753423042345 LBA02-09 EMBARK: A Phase 3 Randomized Study of Enzalutamide or Placebo Plus Leuprolide Acetate and Enzalutamide Monotherapy in High-risk Biochemically Recurrent Prostate Cancer. https://pubmed.ncbi.nlm.nih.gov/37119051/ 177Lu-Labeled Prostate-Specific Membrane Antigen Radioligand Therapy of Metastatic Castration-Resistant Prostate Cancer: Safety and Efficacy. https://pubmed.ncbi.nlm.nih.gov/26795286/
Drs. Neeraj Agarwal and Jeanny Aragon-Ching discuss several key abstracts to be presented at the 2024 ASCO GU Cancers Symposium, including sequencing versus upfront combination therapies for mCRPC in the BRCAAway study, updates on the CheckMate-9ER and CheckMate-214 trials in ccRCC, and a compelling real-world retrospective study in mUC of patients with FGFR2 and FGFR3 mutations. TRANSCRIPT Dr. Neeraj Agarwal: Hello, everyone, and welcome to the ASCO Daily News Podcast. I'm Dr. Neeraj Agarwal, your guest host of the podcast today. I am the director of the Genitourinary Oncology Program and a professor of medicine at the University of Utah's Huntsman Cancer Institute, and editor-in-chief of ASCO Daily News. I am delighted to welcome Dr. Jeanny Aragon-Ching, a genitourinary oncologist and the clinical program director of Genitourinary Cancers at the Inova Schar Cancer Institute in Virginia. Today, we will be discussing key posters and oral abstracts that will be featured at the 2024 ASCO Genitourinary Cancer Symposium, which is celebrating 20 years of evolution in GU oncology this year. You will find our full disclosures in the transcript of this podcast, and disclosures of all guests on the podcast at asco.org/DNpod. Jeanny, it's great to have you on the podcast today to highlight some key abstracts for our listeners ahead of the GU meeting. Dr. Jeanny Aragon-Ching: Thank you so much, Neeraj. It's an honor to be here. Dr. Neeraj Agarwal: Jeanny, as you know, this year we are celebrating the 20th anniversary of the ASCO GU Cancers Symposium, and judging from this year's abstracts, it's clear that this meeting continues to play a major role in advancing GU cancer research. Dr. Jeanny Aragon-Ching: Indeed, Neeraj. This year's abstracts reflect the important strides we have made in GU cancers. So, let's start with the prostate cancer abstracts. What is your takeaway from Abstract 19 on BRCAAway, which will be presented by Dr. Maha Hussein, and of which you are a co-author? As our listeners know, several PARP inhibitor combinations with second-generation androgen receptor pathway inhibitors, or ARPIs, have recently been approved as first-line treatment for patients with metastatic castrate-resistant prostate cancer, or metastatic CRPC, and the question of sequencing PARP inhibitors and ARPIs instead of combining them has emerged. From that perspective, the results of the BRCAAway trial are very important. Can you tell us a little bit more about this abstract, Neeraj? Dr. Neeraj Agarwal: I totally agree with you, Jeanny. The BRCAAway study attempts to answer the crucial questions regarding sequencing versus upfront combination of therapies in the mCRPC setting. It is a phase 2 trial of abiraterone versus olaparib versus abiraterone with olaparib in patients with mCRPC harboring homologous recombination repair mutations. Enrolled patients had mCRPC disease and no prior exposure to PARP inhibitors or ARPIs or chemotherapy in the mCRPC setting and had BRCA1 or BRCA2 or ATM mutations. As previously mentioned, these patients were randomized to 3 arms: abiraterone monotherapy at 1000 milligrams once daily, or olaparib monotherapy at 300 milligrams twice daily, or the combination of abiraterone and olaparib. The primary endpoint was progression-free survival per RECIST 1.1 or Prostate Cancer Working Group 3-based criteria or clinical assessment or death, so, whichever occurred first was deemed to be progression. Secondary endpoints included measurable disease response rates, PSA response rate, and toxicity. This was a relatively small trial with 21 patients in the combination arm, 19 patients in the abiraterone monotherapy arm, and 21 patients in the olaparib monotherapy arm. It should be noted that 26% of patients had received docetaxel chemotherapy in the hormone-sensitive setting, and only 3% of patients had any prior exposure to an ARPI, and these were darolutamide or enzalutamide or in the non-metastatic CRPC setting. The results are very interesting. The median progression-free survival was 39 months in the combination arm, while it was 8.4 months in the abiraterone arm and 14 months in the olaparib arm. An important finding that I would like to highlight is that crossover was also allowed in the monotherapy arms. Of the 19 patients receiving abiraterone, 8 crossed over to receive olaparib, and of the 21 patients receiving olaparib, 8 crossed over to the abiraterone arm. The median PFS from randomization was 16 months in both groups of patients who received abiraterone followed by olaparib or those who received olaparib followed by abiraterone. This is striking when compared to 39 months in patients who started therapy with the combination therapy of abiraterone with olaparib. Dr. Jeanny Aragon-Ching: Thank you so much for that wonderful summary, Neeraj. So the key message from this abstract is that combining olaparib and abiraterone upfront seems to be associated with improvement in PFS compared to just sequencing those agents. Dr. Neeraj Agarwal: Exactly, Jeanny. I would like to add that these results are even more important given that in real-world practice, only half of the patients with mCRPC receive a second-line treatment. Based on these results, upfront intensification with a combination of an ARPI plus a PARP inhibitor in the first-line mCRPC setting seems to have superior efficacy compared to sequencing of these agents. Dr. Jeanny Aragon-Ching: Thank you so much. Now, moving on to a different setting in prostate cancer, there were a couple of abstracts assessing transperineal biopsy compared to the conventional transrectal biopsy for the detection of prostate cancer. So let's start with Abstract 261. Neeraj, can you tell us a little bit more about this abstract? Dr. Neeraj Agarwal: Sure, Jeanny. So, in Abstract 261 titled "Randomized Trial of Transperineal versus Transrectal Prostate Biopsy to Prevent Infection Complications," Dr. Jim Hugh and colleagues led a multicenter randomized trial comparing these 2 approaches, so, transperineal biopsy without antibiotic prophylaxis with transrectal biopsy with targeted prophylaxis in patients with suspected prostate cancer. The primary outcome was post-biopsy infection. Among the 567 participants included in the intention-to-treat analysis, no infection was reported with the transperineal approach, while 4 were detected with the transrectal approach, with a p-value of 0.059. The rates of other complications, such as urinary retention and significant bleeding, were very low and similar in both groups. The investigators also found that detection of clinically significant cancer was similar between the 2 techniques and concluded that the transperineal approach is more likely to reduce the risk of infection without antibiotic prophylaxis. Dr. Jeanny Aragon-Ching: So the key takeaway from this abstract sounds like office-based transperineal biopsy is well-tolerated and does not compromise cancer detection, along with better antibiotic stewardship and health care cost benefits. Moving on to Abstract 273, also comparing these two approaches, what would be your key takeaway message, Neeraj? Dr. Neeraj Agarwal: In this Abstract 273, titled "Difference in High-Risk Prostate Cancer Detection between Transrectal and Transperineal Approaches," Dr. Semko and colleagues found that the transperineal biopsy based on MRI fusion techniques was also characterized by a higher possibility of detecting high-risk prostate cancer and other risk factors as well, such as perineural and lymphovascular invasion or the presence of cribriform pattern, compared to the conventional transrectal method. Dr. Jeanny Aragon-Ching: Thank you, Neeraj. So we can see that the transperineal approach is gaining more importance and could be associated with more benefits compared to the conventional methods. Let's now switch gears to kidney cancer, Neeraj. Dr. Neeraj Agarwal: Sure, Jeanny. Let's start by highlighting Abstract 361, which discusses patient-reported outcomes of the LITESPARK-005 study. So what can you tell us about this abstract, Jeanny? Dr. Jeanny Aragon-Ching: Thank you, Neeraj. So as a reminder to our listeners, based on the LITESPARK-005 trial, it was a Phase 3 trial looking at belzutifan, which is an inhibitor of hypoxia inducible factor 2 alpha or I'll just call HIF-2 alpha for short, was very recently approved by the FDA as a second-line treatment option for patients with advanced or metastatic clear cell renal cell carcinoma after prior progression on immune checkpoint and antiangiogenic therapies. The title of Abstract 361 is "Belzutifan versus Everolimus in Patients with Previously Treated Advanced RCC: Patient-Reported Outcomes in the Phase 3 LITESPARK-005 Study," and this will be presented by Dr. Tom Pells at the meeting. At a median follow-up of 25.7 months, the median duration of treatment with belzutifan was 7.6 months, while it was only 3.9 months with everolimus. At the time of data cutoff date for the second interim analysis, 22.6% of patients remained on belzutifan while only 5% remained on everolimus. In the quality of life questionnaires, the time of deterioration to various quality of life scores, as assessed by standardized scales, was significantly longer in patients randomized to the belzutifan arm compared to those in the everolimus arm. Also, patients in the everolimus arm had worse physical functioning scores. Dr. Neeraj Agarwal: Yes, Jeanny. In addition to the improved outcomes associated with belzutifan, patient-reported outcomes indicate better disease-specific symptoms and better quality of life among patients treated with belzutifan compared to everolimus. This is great news for patients with advanced renal cell carcinoma. Now, Jeanny, can you please tell us about the two abstracts that reported longer follow-up of CheckMate 9ER and CheckMate 214 trials in untreated patients with advanced or metastatic renal cell carcinoma? Dr. Jeanny Aragon-Ching: Yes, Neeraj. So you are referring to Abstracts 362 and 363. Let's start with Abstract 362. This abstract reports the results after a median follow-up of 55 months in the CheckMate 9ER trial, comparing the combination of nivolumab and cabozantinib to sunitinib in patients with advanced RCC without any prior treatment, so first-line therapy. The primary endpoint was PFS per RECIST 1.1 as assessed by an independent central review. So there were key secondary outcomes including overall survival (OS), objective response rates, and safety. Consistent with prior analysis at a median follow-up time of 18.1 and 44 months, the combination of nivolumab and cabozantinib at a median follow up of 55.6 months continues to show a significant reduction in the risk of progression or death by 42% and in the risk of death by 23% compared to sunitinib. Dr. Neeraj Agarwal: And Jeanny, what can you tell us about the efficacy results of this combination by IMDC risk categories? Dr. Jeanny Aragon-Ching: Similar to prior results in patients with intermediate to poor risk IMDC risk category, the combination treatment maintained significant efficacy and reduced the risk of progression or death by 44% and the risk of death by 27%. To put it simply, the update now shows a 15-month improvement in overall survival with the cabozantinib-nivolumab combination compared to sunitinib, which is amazing. Also, in patients with favorable IMDC risk group, which represented truly a small number of patients in the trial, there was a strong trend for improvement of outcomes as well. I would like to point out that no new safety concerns were identified. Dr. Neeraj Agarwal: So, it looks like the key message from this abstract is that with longer follow-up, the combination of nivolumab and cabozantinib maintains a meaningful long-term efficacy benefit over sunitinib, supporting its use for newly diagnosed patients with advanced or metastatic renal cell carcinoma. Let's move on to Abstract 363, which compares nivolumab with ipilimumab to sunitinib in first-line advanced renal cell carcinoma. What would you like to tell us about this abstract, Jeanny? Dr. Jeanny Aragon-Ching: Yes, Neeraj. The title of this abstract is "Nivolumab plus Ipilimumab versus Sunitinib for the First-Line Treatment of Advanced RCC: Long-Term Follow-Up Data from the Phase 3 CheckMate 214 Trial." In this abstract, Dr. Tannir and colleagues report outcomes with the longest median follow-up in first-line advanced RCC setting for any clinical trial. So the median follow-up now is about 18 months. The primary endpoints were OS, PFS, and objective response rates, as assessed by an independent review according to RECIST 1.1 criteria in the intermediate to poor risk IMDC risk group, which is the intent-to-treat (ITT) analysis, while secondary outcomes included the same outcomes in the ITT population of patients. Although the progression-free survival was similar in both arms, the combination of nivolumab-ipilimumab reduced the risk of death by 28% compared to sunitinib in the ITT population of patients. When stratifying the results by IMDC risk groups, the combination arm of nivolumab-ipilimumab showed significant improvement in the intermediate to poor risk group, but there was no difference in the favorable risk group. But in the study, no new safety signals were identified. Dr. Neeraj Agarwal: Thank you, Jeanny, for such a comprehensive description of the results of these two studies. I'd like to add that the median overall survival of patients with metastatic renal cell carcinoma in the ITT population in the CheckMate 214 trial has now reached 53 months, which would have been unimaginable just a decade ago. This is wonderful news for our patients. So the key takeaway from these two abstracts would be that immune checkpoint inhibitor-based combinations remain the backbone of first-line advanced renal cell carcinoma treatment. Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. This is wonderful news for all of our patients, especially for those who are being treated for first-line therapy. Now, let's move on to the bladder cancer abstracts. We have two exciting abstracts from the UNITE database. What are your insights on Abstract 537, titled "Outcomes in Patients with Advanced Urethral Carcinoma Treated with Enfortumab Vedotin After Switch-Maintenance of Avelumab in the UNITE Study"? Dr. Neeraj Agarwal: As our listeners know, enfortumab vedotin is an antibody-drug conjugate that binds to a protein called Nectin 4 expressed on bladder cancer cells. In this abstract, Dr. Amanda Nizam and colleagues describe outcomes in 49 patients receiving third-line enfortumab vedotin after prior progression on platinum-based therapy and maintenance avelumab. At a median follow-up of 8.5 months, the median progression-free survival was 7 months and the median overall survival was 13.3 months with enfortumab vedotin in this treatment-refractory setting, the objective response rates were 54%. The message of this study is that enfortumab vedotin is an effective salvage therapy regimen for those patients who have already progressed on earlier lines of therapies, including platinum-based and immunotherapy regimens. Dr. Jeanny Aragon-Ching: Thank you, Neeraj, for that comprehensive review. I want to focus on another patient population in the UNITE database, which is the use of fibroblast growth factor receptor (FGFR) alterations. Can you tell us more about the sequencing now of erdafitinib and enfortumab vedotin in these patients with metastatic urothelial cancer, as discussed in Abstract 616? Dr. Neeraj Agarwal: Sure, Jeanny. As a reminder, erdafitinib is a fibroblast growth factor receptor kinase inhibitor approved for patients with locally advanced or metastatic urothelial carcinoma harboring FGFR2 or FGFR3 alterations after progression on platinum-based chemotherapy. However, the optimal sequencing of therapies in these patients is unclear, especially with enfortumab vedotin being approved in the salvage therapy setting and now in the frontline therapy setting. So in this retrospective study, all patients with metastatic urothelial carcinoma had FGFR2 or FGFR3 alterations. Dr. Cindy Jiang and colleagues report outcomes in 24 patients receiving enfortumab vedotin after erdafitinib, 15 patients receiving erdafitinib after enfortumab vedotin, and 55 patients receiving enfortumab vedotin only. This is a multicenter national study. Interestingly, patients receiving both agents had a longer overall survival in a multivariate analysis, regardless of the treatment sequencing, than patients receiving enfortumab vedotin alone or only with a hazard ratio of 0.52. The objective response rate of enfortumab vedotin in the enfortumab vedotin monotherapy arm was 49%. When these agents were sequenced, the objective response with enfortumab vedotin was 32% after erdafitinib and 67% when used before erdafitinib. Dr. Jeanny Aragon-Ching: Thank you so much, Neeraj. I think these are important real-world data results, but I would like to point out that larger and prospective studies are still needed to confirm these findings, especially regarding the outcome of erdafitinib after enfortumab vedotin, particularly when the latter is used in the first-line setting. Dr. Neeraj Agarwal: I totally agree, Jeanny. Now, let's discuss some abstracts related to disparities in the management of patients with genitourinary cancers. Dr. Jeanny Aragon-Ching: Sure, actually, I would like to discuss 2 abstracts related to disparities in patients with prostate cancer. So the first one, Abstract 265, titled "Patient-Provider Rurality and Outcomes in Older Men with Prostate Cancer." In this study, Dr. Stabellini, Dr. Guha and the team used a SEER Medicare-linked database that included more than 75,000 patients with prostate cancer. The primary outcome was all-cause mortality, with secondary outcomes included prostate cancer-specific mortality. The investigators showed that the all-cause mortality risk was 44% higher in patients with prostate cancer from rural areas who had a provider from a non-metropolitan area compared to those who were in a metropolitan area and had a provider also from a metropolitan area. Dr. Neeraj Agarwal: Those are very important data and highlight the healthcare disparities among the rural population with prostate cancer that still exist. So what is your key takeaway from Abstract 267, titled "Rural-Urban Disparities in Prostate Cancer Survival," which is a population-based study? Dr. Jeanny Aragon-Ching: Of course. This abstract discusses, actually, a very similar issue regarding access to healthcare among rural versus urban patients. In this study, Dr. Hu and Hashibe and colleagues and team at the Huntsman Cancer Institute assessed all-cause death and prostate cancer-related death risk in a retrospective study in which patients with prostate cancer based on rural versus urban residencies looked at 18,000 patients diagnosed with prostate cancer between 2004 and 2017. 15% lived in rural counties. Similar to the prior abstract we talked about, patients living in rural areas had about a 19% higher risk of all-cause mortality and a 21% higher risk of prostate cancer-specific mortality in comparison to patients living in urban areas. Dr. Neeraj Agarwal: So Jeanny, we can say that both of these abstracts, led by different groups of investigators, highlight that patients with prostate cancer living in rural areas have inferior survival outcomes compared to those living in urban areas, and it is time to focus on the disparities experienced by the rural population with prostate cancer. Dr. Jeanny Aragon-Ching: Yeah, absolutely Neeraj. I concur with your thoughts. So, any final thoughts before we wrap up the podcast today? Dr. Neeraj Agarwal: Yes, before concluding, Jeanny, I want to express my gratitude for your participation and the valuable insights you have shared today. Your contributions are always appreciated, and I sincerely thank you for taking the time to join us today. As we bring this podcast to a close, I would like to highlight the significant advances happening in the treatment of patients with genitourinary cancers during our upcoming 2024 ASCO GU meeting. Many studies featuring practice-impacting data will be presented by investigators from around the globe. I encourage our listeners to not only participate at this event to celebrate these achievements, but to also play a role in disseminating these cutting-edge findings to practitioners worldwide. By doing so, we can collectively maximize the benefit for patients around the world. And thank you to our listeners for joining us today. You will 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. Thank you very much. Disclaimer: The purpose of this podcast is to educate and inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guest speakers express their own opinions, experience, and conclusions. Guest statements on the podcast do not necessarily reflect 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 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.
Tá gnó feola 'Micilín Muc' a dúnadh san Earrach. Deir Séamus Mac Gearailt go bhfuil athrú tagtha air chúrsaí gnó,agus ana chuid dá gcustaiméirí ag eirí as a ngnótha féin. Deir sé go raibh gnó maith aige agus go mbeadh sé oiriúnach do dhaoine óga.
Séamus MacGearailt;Comhlucht Micilín Muc a dúnadh.Joan Uí Shuilleabháin;Mórchuaird tarracóra Chorca Dhuibhne. Dr. Síle de Cléir;Seanscéalta iontais na Gaeltachta. Cúrsaí bólála i Muscraí,agus Cill na Martra prappáil do chluiche an Domhnaigh
In this special podcast, UROONCO BCa chief editor Dr. Benjamin Pradere (FR) talks with Prof. Thomas Powles (GB) about the positive results of the EV-302/KEYNOTE-A39 trial that were announced at ESMO 2023. Prof. Powles shares details on the rationale and design of the EV-302/KEYNOTE-A39 study: an open-label, randomised, controlled, phase 3 study evaluating enfortumab vedotin in combination with pembrolizumab (EV+P) versus chemotherapy in patients with previously untreated locally advanced metastatic urothelial carcinoma (la/mUC).The dual endpoints of this trial are overall survival (OS) and progression-free survival (PFS) per RECIST (response evaluation criteria in solid tumours) v 1.1 by blinded independent central review (BICR). Prof. Powles: "The topline results from the EV-302/KEYNOTE-A39 trial are encouraging for patients with advanced-stage urothelial cancer, which is aggressive and associated with devastating outcomes."For more details on this study, you can read the abstract on the UROONCO Bladder Cancer educational platform.
On this episode Kevin & Pete are joined by long time friend and experienced Elk hunter, Muc Simons. Muc has guided elk all over the west of both Canada and the US. He shares comparisons in chasing bugling bulls in western Canada and south into the states, including places like Arizona. Muc gives us tips on calling and locating. He shares a few great stories including a successful hunt with Cody Robbins on his massive 7 point bull. For more on Muc go to.... https://www.instagram.com/muc_simons/ https://www.youtube.com/@muc100/videos https://www.facebook.com/AlloutdoorswithMuc/ As always be sure to check out our sponsors and use the promo codes... https://akuoutdoor.ca/ Use Promocode FOCUS for 15% off Hunting & Military Boots https://akuoutdoor.us/ Use Promocode FOCUS for 15% off Hunting & Military Boots https://www.treelineacademy.net/ use promocode "FOCUS22" and get $20USD off the course Elk101.com | Dedicated to Elk Hunting Information use the promocode "focus" and receive 20% off the online course This episode of the Focus Hunting Podcast is brought to you by: Hard Core Archery Howl For Wildlife Learn more about your ad choices. Visit megaphone.fm/adchoices
Welcome back Lets Talk Physical Media, This week we have a great show for you. First of all Faith is Back! Second, Clerks is getting a brand New Trilogy box set, While Mission Impossible Dead Reckoning part 1 gets an official release date. Faith and John answer your questions including what is their top 5 Horror movies to watch in October? All that and much MUC! more. EMAIL - letstalkentmt@gmail.comInstagram https://instagram.com/letstalkentertainmentandmedia?utm_medium=copy_linkFaceboook https://www.facebook.com/Letstalkentmt/Twitter: https://twitter.com/letstalkentmtAPPLE PODCAST LINK https://podcasts.apple.com/us/podcast/lets-talk-entertainment-and-media/id1667124623PANDORA LINK https://www.pandora.com/podcast/lets-talk-entertainment-and-media/PC:1001053804Digital code Give Away: Every week we give away a digital code. On Fridays video we will announce the Movie and the question you will have to answer in the comments section. Then on Mondays video we will announce the winner and how you will receive the video code. Also Keep an eye out for major give aways as the channel reaches its goals witch we can't do without all of you, so thank you for your support.
Chapters listed below. Subscribe so we can give away a full suspension bike at 1k Todays delivery from our bike vendor has a range of products. We start with tires for a bike packing customer and our favorite lube at the shop to keep him going. My least favorite shop product came in for repair bikes. The discussion of picking out flat pedals for mountain biking came next. Listen in for the rest ;) Chapters 00:00 Intro 01:40 Maxxis Ardent Race Tubeless MTB Tire 03:44 Garmin Vivosmart 5 and Instinct Crossover 04:24 Shimano Alivio Front Derailleur 05:28 SRAM X3 9 Speed Rear Derailleur 06:23 Raceface Chesters Pedals and How to Choose Mountain Bike Pedals 08:43 Alloy vs Composite MTB pedals 09:45 Rock N Roll Holy Cow Bicycle Chain Lube 14:15 Muc-off Drivetrain Cleaner 14:55 Raceface 104 BCD Chainring 15:08 SRAM MRX Grip Shifters 15:47 Muc-off Tubeless Valve Stems 18:06 Measuring Replacement Seat Post Collars 19:19 G-Form Pro X-3 Knee Pad 20:08 Outro and Subscriber Giveaway at 1k
Reels, Booze & Bro's aka RB2 hosts Jay and Brian with Reel Bro Fan Kev review the greatest superhero movie team-up in this latest episode; The Avengers. Grab your beverage and see why it's such a great one.Support the show
Cecil Burch is back on for his 4th appearance to talk about his new JiuJitsu academy, Gracie University affiliation. We also talk about his collaboration with Darryl Bolke and Chuck Haggard for their NPE Counter Robbery course. The course teaches you to think with a gun in your hand, make critical shoot, no shoot decisions, how to manage unknown contacts (MUC), use pepper spray properly all while considering being in an environment that is non-permissive where you may not be able to carry a full size blaster. The course also has a force on force element that uses blue guns which aids in getting folks under pressure without being overly physical. That Weems Guy Podcast - NPE Counter Robbery Discussion https://podcasters.spotify.com/pod/show/lee-weems/episodes/NPE-Counter-Robbery-e1i5290/a-a7sigi3 NPE Counter Robbery AAR blog post https://www.primerpeak.com/npe-counter-robbery-with-burch-bolke-haggard-2023/ Also for more info on Cecil's course work and his academy: https://www.iacombatives.com/ https://gjjnphx.com/ Check out Cecil's awesome YouTube channel: https://www.youtube.com/@immediateactioncombatives5378/featured Cecil Burch is a like long martial artist training in a multitude of systems for over 40 years. Some of the systems have been Jeet Kune Do and Filipino Martial Arts under Dan Inosanto and Paul Vunak, he has trained in Thaiboxing, western boxing, Sevate and Pentjak Silat and many more. Currently Cecil's primary focus is Brazilian Jiu-Jitsu in which he has a Black Belt under the legendary Megaton Diaz. Furthermore Cecil is an avid shooter and is a part of the Shivworks Collective which is a scholarship of the finest minds in integrated martial arts, combining combative sports modalities with force on force stress inoculation using sims guns and training blades to pressure test those modalities. Intro and Outro Music by: The Tactical Twins, Jason Bieler and The Baron Von Bielski Orchestra and Tim Alexander/Fata Morgana Please subscribe and share our podcast with friends and family. Visit our website for bios, future events and info at www.evosec.org Like, follow and share us on Facebook and Instagram @evosecusa WE ARE PUMPED TO HAVE A NEW AFFILIATE LINK FOR ORIGIN AND JOCKO FUEL!!! Help support this show by purchasing any of your JiuJitsu gear, Jocko Supplements, books clothing and more... link below. Origin/Jocko Fuel – Bringing back American manufacturing, producing the best Jiu-Jitsu Gis on the market, Jeans, rash guards, and world class supplements to help you on the path. Use EvoSec10 at checkout for 10% off, this helps us greatly. EVOSEC Originusa.com AFFILIATE LINK Tenicor – www.tenicor.com they are educators, and innovators in the holster market. They are firearms instructors themselves, pressure testing their gear in multiple force on force events every year. We support those who do the work. Again, patronizing our sponsors helps us greatly. Evolution Security is Eric Davis, Aaron Davis and Brian Schilt; specializing in self-protection education, defensive pistol and carbine, consulting, and weapons based grappling. Their mission is to help those serious about protecting themselves and their loved ones, become more capable though filtered information, recommended study, and highlighting their mentors who are the best in the field. In addition, Eric and Aaron (twins) are musicians keeping with Musashi's adage that martial artist should focus on art outside of the martial.
In this podcast, UROONCO BCa chief editor Dr. Benjamin Pradere (FR) talks to Dr. Arlene O. Siefker-Radtke (US) from the Depart. of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston. She answers questions about the recent ASCO23 presentations on metastatic urothelial cancer (mUC), where new results of the phase II Norse study, and the phase III THOR study were shared.Phase II Norse study:Dr. Siefker-Radtke elaborates on the study rational and pleasing results of the phase II Norse study: Erdafitinib (erda) vs erda plus cetrelimab (erda+CET) for patients with metastatic urothelial carcinoma (mUC) and fibroblast growth factor receptor alterations (FGFRa). Single agent erdafitinib had an objective response rate of around 45%. The combination of erdafitinib and cetrelimab had an objective response rate of around 55%. Single agent erdafitinib had a progression-free survival (PFS) of around 5.5 months, and the combination arm had a median survival of around 11 months. The median overall survival with erdafitinib alone was around 16 months, whereas the combination had a median overall survival of around 20.8 months.Phase III THOR study: Dr. Siefker discusses the phase III results whereby erda significantly improved overall and PFS, as well as overall response rate, compared with chemotherapy, in patients with advanced or mUC and FGFR alteration who already had been treated with a PD-(L)1 inhibitor. For more details on these studies, you can read the abstracts on the UROONCO educational platform - phase II Norse, phase III THOR.
Spring Bears Series PART THREE. On this installment of our spring bear series, we are joined again by Marcus "Muc" Simons. Muc talks about his four-year pursuit of a monster bear he named Warpig. This hunt was four years in the making and after many close encounters and heartache Muc was finally able to connect. Muc shares his baiting setups and talks about his stands. Great information for those who are able to bait spring black bears. For more on Muc go to... https://www.instagram.com/muc_simons/ https://www.youtube.com/@muc100/videos https://www.facebook.com/AlloutdoorswithMuc/ As always be sure to check out our sponsors and use the promo codes... https://akuoutdoor.ca/ Use Promocode FOCUS for 15% off Hunting & Military Boots https://akuoutdoor.us/ Use Promocode FOCUS for 15% off Hunting & Military Boots https://www.treelineacademy.net/ use promocode "FOCUS22" and get $20USD off the course Elk101.com | Dedicated to Elk Hunting Information use the promocode "focus" and receive 20% off the online course This episode of the Focus Hunting Podcast is brought to you by: Hard Core Archery Howl For Wildlife Learn more about your ad choices. Visit megaphone.fm/adchoices
Go online to PeerView.com/KPE860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Management of advanced/metastatic urothelial cancer has undergone a significant transformation with the addition of PD-1– and PD-L1–targeting immune checkpoint inhibitors (ICIs) to the treatment armamentarium. These advances are quickly moving into early-stage disease, including emerging bladder-sparing and perioperative approaches, which has recently led to the first regulatory approval of an ICI as adjuvant therapy in high-risk muscle-invasive bladder cancer (MIBC). In this activity, based on a recent live symposium, experts use real-world cases and mini lectures to illustrate practical tips and treatment selection strategies for patients with MIBC or NMIBC (non–muscle-invasive bladder cancer), including clinical trial opportunities, bladder-preservation options, and perioperative regimens. This activity also examines approaches for personalized care in metastatic urothelial cancer (mUC), both in the frontline setting and in progressive disease. Upon completion of this activity, participants should be better able to: Assess new evidence on therapeutic strategies for bladder cancer management across the disease continuum based on innovative drug delivery approaches, modern immunotherapy regimens, and novel targeted agents; Implement novel and emerging therapeutic approaches into personalized treatment plans for patients with varying stages of bladder cancer considering the available evidence, current guidelines, and principles of multidisciplinary and patient-centered care; and Integrate evidence- and team-based management protocols to address the unique suite of adverse events associated with novel therapeutics for bladder cancer
Go online to PeerView.com/KPE860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Management of advanced/metastatic urothelial cancer has undergone a significant transformation with the addition of PD-1– and PD-L1–targeting immune checkpoint inhibitors (ICIs) to the treatment armamentarium. These advances are quickly moving into early-stage disease, including emerging bladder-sparing and perioperative approaches, which has recently led to the first regulatory approval of an ICI as adjuvant therapy in high-risk muscle-invasive bladder cancer (MIBC). In this activity, based on a recent live symposium, experts use real-world cases and mini lectures to illustrate practical tips and treatment selection strategies for patients with MIBC or NMIBC (non–muscle-invasive bladder cancer), including clinical trial opportunities, bladder-preservation options, and perioperative regimens. This activity also examines approaches for personalized care in metastatic urothelial cancer (mUC), both in the frontline setting and in progressive disease. Upon completion of this activity, participants should be better able to: Assess new evidence on therapeutic strategies for bladder cancer management across the disease continuum based on innovative drug delivery approaches, modern immunotherapy regimens, and novel targeted agents; Implement novel and emerging therapeutic approaches into personalized treatment plans for patients with varying stages of bladder cancer considering the available evidence, current guidelines, and principles of multidisciplinary and patient-centered care; and Integrate evidence- and team-based management protocols to address the unique suite of adverse events associated with novel therapeutics for bladder cancer
PeerView Kidney & Genitourinary Diseases CME/CNE/CPE Video Podcast
Go online to PeerView.com/KPE860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Management of advanced/metastatic urothelial cancer has undergone a significant transformation with the addition of PD-1– and PD-L1–targeting immune checkpoint inhibitors (ICIs) to the treatment armamentarium. These advances are quickly moving into early-stage disease, including emerging bladder-sparing and perioperative approaches, which has recently led to the first regulatory approval of an ICI as adjuvant therapy in high-risk muscle-invasive bladder cancer (MIBC). In this activity, based on a recent live symposium, experts use real-world cases and mini lectures to illustrate practical tips and treatment selection strategies for patients with MIBC or NMIBC (non–muscle-invasive bladder cancer), including clinical trial opportunities, bladder-preservation options, and perioperative regimens. This activity also examines approaches for personalized care in metastatic urothelial cancer (mUC), both in the frontline setting and in progressive disease. Upon completion of this activity, participants should be better able to: Assess new evidence on therapeutic strategies for bladder cancer management across the disease continuum based on innovative drug delivery approaches, modern immunotherapy regimens, and novel targeted agents; Implement novel and emerging therapeutic approaches into personalized treatment plans for patients with varying stages of bladder cancer considering the available evidence, current guidelines, and principles of multidisciplinary and patient-centered care; and Integrate evidence- and team-based management protocols to address the unique suite of adverse events associated with novel therapeutics for bladder cancer
Go online to PeerView.com/KPE860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Management of advanced/metastatic urothelial cancer has undergone a significant transformation with the addition of PD-1– and PD-L1–targeting immune checkpoint inhibitors (ICIs) to the treatment armamentarium. These advances are quickly moving into early-stage disease, including emerging bladder-sparing and perioperative approaches, which has recently led to the first regulatory approval of an ICI as adjuvant therapy in high-risk muscle-invasive bladder cancer (MIBC). In this activity, based on a recent live symposium, experts use real-world cases and mini lectures to illustrate practical tips and treatment selection strategies for patients with MIBC or NMIBC (non–muscle-invasive bladder cancer), including clinical trial opportunities, bladder-preservation options, and perioperative regimens. This activity also examines approaches for personalized care in metastatic urothelial cancer (mUC), both in the frontline setting and in progressive disease. Upon completion of this activity, participants should be better able to: Assess new evidence on therapeutic strategies for bladder cancer management across the disease continuum based on innovative drug delivery approaches, modern immunotherapy regimens, and novel targeted agents; Implement novel and emerging therapeutic approaches into personalized treatment plans for patients with varying stages of bladder cancer considering the available evidence, current guidelines, and principles of multidisciplinary and patient-centered care; and Integrate evidence- and team-based management protocols to address the unique suite of adverse events associated with novel therapeutics for bladder cancer
PeerView Kidney & Genitourinary Diseases CME/CNE/CPE Audio Podcast
Go online to PeerView.com/KPE860 to view the activity, download slides and practice aids, and complete the post-test to earn credit. Management of advanced/metastatic urothelial cancer has undergone a significant transformation with the addition of PD-1– and PD-L1–targeting immune checkpoint inhibitors (ICIs) to the treatment armamentarium. These advances are quickly moving into early-stage disease, including emerging bladder-sparing and perioperative approaches, which has recently led to the first regulatory approval of an ICI as adjuvant therapy in high-risk muscle-invasive bladder cancer (MIBC). In this activity, based on a recent live symposium, experts use real-world cases and mini lectures to illustrate practical tips and treatment selection strategies for patients with MIBC or NMIBC (non–muscle-invasive bladder cancer), including clinical trial opportunities, bladder-preservation options, and perioperative regimens. This activity also examines approaches for personalized care in metastatic urothelial cancer (mUC), both in the frontline setting and in progressive disease. Upon completion of this activity, participants should be better able to: Assess new evidence on therapeutic strategies for bladder cancer management across the disease continuum based on innovative drug delivery approaches, modern immunotherapy regimens, and novel targeted agents; Implement novel and emerging therapeutic approaches into personalized treatment plans for patients with varying stages of bladder cancer considering the available evidence, current guidelines, and principles of multidisciplinary and patient-centered care; and Integrate evidence- and team-based management protocols to address the unique suite of adverse events associated with novel therapeutics for bladder cancer
Hãy tưởng tượng, đây là bạn và bạn đang đứng trước một năm mới vừa sang, một năm mới hoan hỉ, một chương mới tinh tươm đang chờ bạn đặt bút. Và bạn thật sự đặt bút, bạn viết xuống hàng loạt dự định, mục tiêu cho chặng đường 12 tháng đầy háo hức của mình. Thế rồi những ngày đầu, tuần đầu, hay những tháng đầu tiên, bạn thực hiện vô cùng quyết tâm và hăng say. Thế nhưng, chỉ sau một khoảng thời gian có thể là rất ngắn, mọi thứ liền quay trở lại theo lề lối cũ. Bạn dần chệch hướng với những kế hoạch để chinh phục mục tiêu của mình, thế nhưng mặc cho mọi thứ đang dần đi lệch, bạn cũng tặc lưỡi hiển nhiên cho qua và thầm nghĩ "Thôi kệ, để năm sau lại cố tiếp vậy". ______________ Khám phí bí kíp "lên sàn" Thương mại Điện tử cùng cuốn sách mới nhất của Nhà Nhện tại: https://b.link/SP-YT-Ecom Ghé Nhà sách Spiderum trên SHOPEE ngay thôi các bạn ơi: https://shorten.asia/RFfT4NVT _____________ Bài viết: Mục tiêu lớn, nỗ lực ảo Được viết bởi: ChuyentuTam Link bài viết: https://spiderum.com/bai-dang/Muc-tieu-lon-no-luc-ao-7GpY67hACZyK ______________ Giọng đọc: Samurice Editor: Nguyễn Sơn --- Send in a voice message: https://anchor.fm/spiderum/message Support this podcast: https://anchor.fm/spiderum/support
This educational session will comprehensively evaluate the current state of the bladder cancer management paradigm and investigate the emergence of new data across the totality of the disease continuum, with a particular emphasis on evidence-based treatment sequencing and the role of antibody-drug conjugates (ADCs) in subsequent lines of therapy for advanced disease. To conclude the session, activity attendees will get to apply the therapeutic principles they've learned to real-world clinical scenarios which will focus on patient-centric treatment selection and sequencing, as well as recognition, mitigation, and management of treatment-related adverse events.1.50 AMA PRA Category 1 Credit™1.50 ParticipationCollect credit: https://www.ceconcepts.com/gu-cancer23-podcast
Super bowl! Spiderman 4 joker 2 news!!!!!MUC talk!!!!!
Bereit für einen neuen knackigen UX Snack? Auch heute erwartet dich wieder geballtes UX Wissen in nicht mehr als 5 Minuten. Viel Spaß! UNSER GAST HEUTE Dominique Winter + Product Development Coach bei OBI und + Content Creator + Coach für Product Owner und Product Leader + https://www.linkedin.com/in/dominiquewinter/ THEMEN + Was sind UX Culture Hacks + Welche Denkanstöße hat die MuC 22 geliefert? IN EIGENER SACHE - FEEDBACK GEBEN UND GEWINNEN Gib uns bitte Feedback zum Podcast: https://forms.gle/PJLKxrADXVNL5ek26
JCO PO author Dr. Shilpa Gupta, MD, Associate Professor of Medicine at the Cleveland Clinic and GU Medical Oncology Director, shares analysis on outcomes in real-world settings for metastatic urothelial carcinoma (mUC) patients. Host Dr. Rafeh Naqash and Dr. Gupta discuss the utility of tumor mutational burden (TMB) to determine treatment, and mUC patient response from immune checkpoint inhibitors (ICPI) as compared with carboplatin. Click here to read the article! TRANSCRIPT Dr. Rafeh Naqash: Hello and welcome to JCO Precision Oncology Conversations. I am Dr. Rafeh Naqash, assistant professor of medicine at OU Stephenson Cancer Center. You're listening to the JCO Precision Oncology Conversations podcast. Today I'll be talking with Dr. Shilpa Gupta, who is an associate professor of medicine at the Cleveland Clinic and also the GU Medical Oncology Director. And we'll be talking about their group's recent paper, ‘Tumor Mutational Burden as a Predictor of First-Line Immune Checkpoint Inhibitor Versus Carboplatin Benefit in Cisplatin-Unfit Patients With Urothelial Carcinoma'. Full disclosures for our guest can be found on the article's publication page. Hello and welcome to the podcast, Dr. Gupta. It's nice to have you here. For the sake of this podcast, we'll be referring to each other using our first names. So welcome and thanks for joining us today. Dr. Shilpa Gupta: It's my pleasure to be here, Rafeh, I'm really excited about chatting about this paper with you. Thank you for the opportunity. Dr. Rafeh Naqash: Thank you so much. So today we'll be discussing this interesting publication of yours, talking about biomarkers. And I often refer to biomarkers as the Pandora's Box for immune checkpoint inhibitors because definitely one size does not fit all. And reading through your paper, I saw a lot of interesting findings that you have defined in this publication. But for starters, what was the premise and background of why you wanted to study this question of tumor mutational burden as a biomarker in this patient population? Dr. Shilpa Gupta: Yeah, that's a great question, Rafeh. The treatment paradigm for urothelial cancer patients has really evolved over the last many years. For example, patients who are eligible to receive cisplatin-based chemotherapy, that's the treatment of choice. And for patients who are not eligible to receive cisplatin due to a variety of reasons like chronic kidney disease, heart failure, peripheral neuropathy, poor performance status, or hearing loss, in the past, we used to treat them with gemcitabine and carboplatin, but outcomes were quite dismal with median overall survival less than six months or so. And then in 2017, the approval of pembrolizumab and atezolizumab as single agents was welcome news because these patients had more durable responses and survival was longer than historically with gemcitabine-carboplatin. And this is what became the standard of care based on the FDA expedited approval. However, in 2018, the FDA restricted the use of immunotherapy only to those patients whose tumors had high PD-L1 or who were not eligible to receive carboplatin, based on the interim analysis from the phase three trials IMvigor130, which compared atezolizumab to gemcitabine-carboplatin, one of the cohorts for cis-ineligible patients, and KEYNOTE-361, which compared pembrolizumab to gemcitabine-carboplatin in the cis-ineligible cohort. And furthermore, recently, the FDA actually further restricted the label for pembrolizumab, because in the phase 3 study, even in high PD-L1 subgroups, pembrolizumab did worse than gemcitabine-carboplatin, regardless of their PD-L1 status. There were early deaths, lower response rates, and in the IMvigor130 study, we recently saw that atezolizumab was actually withdrawn for this indication altogether. So there has been this attraction for PD-L1 for a long time, but now multiple studies in urothelial cancer have shown that PD-L1 is not a durable biomarker. And we wanted to see if there's other biomarkers which can be accessible at the point of care. And we wanted to study how tumor mutational burden can or cannot pan out as a treatment selection or complementary to clinical criteria. Right now, there's no biomarkers to guide treatment for patients in urothelial cancer for carboplatin or immunotherapy use. And that was the premise for the study. Dr. Rafeh Naqash: Excellent. Thank you so much for that detailed understanding of why you decided to pursue this. Now, from the listener standpoint when you define cisplatin-ineligible patients, in your practice, what is the percentage of patients that you see who are technically cisplatin-ineligible? Does comorbidity play an important role in determining which patients, or does it depend on your discussion with the patient? What are those factors that you would describe to define what cisplatin-ineligibility would constitute? Dr. Shilpa Gupta: So historically, Matt Galsky and colleagues described cisplatin-ineligibility as patients with a creatinine clearance less than 60 mLs per minute, hearing loss greater than grade two, poor ECOG performance status two or higher, peripheral neuropathy, which is significant or significant heart failure. Now, those all make patients ineligible for cisplatin. Now, more recently, we know that we can safely give cisplatin as long as creatinine clearance is above 50. So for the real world, 50 is a threshold where we can use split dose cisplatin. And I'll say, given that bladder cancer or urothelial cancer is a disease of the elderly, median age being 71 years, a lot of our patients have these comorbidities, chronic kidney disease, diabetes, and whatnot, which precludes us from using cisplatin. So in the real world, I would say that around 50% of patients are ineligible to receive cisplatin. Dr. Rafeh Naqash: Interesting. And that goes back to the point where not everything that resulted from clinical trials, or the data that we get, may not be exactly applicable to the real world patient population, as you have pointed out in this interesting paper. So going back to the manuscript now from a methodology perspective, what kind of data did you include to get to the results that we'll talk about next? What was the inclusion and what was the patient population in this analysis? Dr. Shilpa Gupta: So the patient population basically were patients who had a confirmed diagnosis of metastatic urothelial cancer. And the databases we used were the US-wide Flatiron Foundation Medicine Clinical Genomic Database, which has patients who were listed as metastatic urothelial cancer. But in addition, they also had genomic testing performed from their tumors, and results were available. And we accessed the database between 2011 until April 2021. And all these patients had had genomic testing using Foundation Medicine assay. And this de-identified data was basically US-wide across 280 cancer clinics and that's around 800 sites of care. And there's a whole range of retrospective longitudinal clinical data that was available, derived from the electronic health records comprising patient-level structured and unstructured data and also their genomic information from the tumors. And there was clinical data including demographics, lab values, performance status, timing of treatment, exposure, as well as time of progression and survival. We decided to include patients if they received a frontline single agent immunotherapy, no matter what it was, whether pembrolizumab, atezolizumab, Nivolumab, durvalumab or avelumab, or a carboplatin-based chemotherapy. And just for the readers, this is a retrospective review. So we just used these selected patients who got in these therapies. We also required that these patients had tumor mutational burden information available through the tissue biopsy and patients who received chemotherapy and immunotherapy together were excluded and details are present in the manuscript, but this was pretty much the broad selection criteria. Dr. Rafeh Naqash: Thank you so much. And definitely a very representative patient population from a real world setting with different therapy and different other clinical variables that are relevant in the real world setting. So from an analysis standpoint, you, from what I read, define both a predictive and a prognostic aspect to tumor mutational burden. Could you tell us more about those results and highlight some of the interesting findings from that perspective? Dr. Shilpa Gupta: Yes, absolutely. So as you know, tumor mutation burden cut off of ten mutations per megabase is currently utilized by the FDA, whereby approval of pembrolizumab for tumor agnostic condition was made. So that's what we considered high versus low. And we found that in this, after propensity weighing in, the tumor mutational burden less than ten group, basically those patients did not benefit from checkpoint inhibitor single agent as compared to tumor mutational burden of ten or greater. And so basically, we found that patients who had tumor mutational burden ten or higher overall had more favorable progression-free survival time to next treatment, as well as overall survival when they got a single agent immune checkpoint inhibitor, as opposed to those who got carboplatin, and also when compared to those who had tumor mutational burden less than ten. So we also looked at PD-L1 information available from the genomic database, but it was only available for around 35% of patients and still we were able to see that PD-L1 did not correlate with any of these outcomes as we show in the paper. Dr. Rafeh Naqash: I see. And as you mentioned, you show both time to treatment failure PFS being better in TMB high patients defined as ten mutations per megabase. I didn't specifically see results related to TMB high versus low in a carboplatin specific cohort. Is that analysis something that was looked at and trying to understand whether neoantigens in a platinum-based setting specifically make a difference whether high TMB is predictive there in the carboplatin setting. Was that looked at? Dr. Shilpa Gupta: So yes, we looked at, in the Figure 4, for the comparison of the TMB and which we were looking at the checkpoint inhibitor versus chemo. So for TMB low the chemotherapy cohort had more favorable results. Is this what you were getting at? Dr. Rafeh Naqash: Yeah, I think what I was specifically trying to look at, like you have shown in the paper, is TMB is predictive of benefit with checkpoint inhibitors and is also prognostic in the checkpoint inhibitor setting. So my question was more whether it had a prognostic implication in a carboplatin specific cohort. So meaning high TMB, whether it correlated with better outcomes with carboplatin therapy versus low TMB. So if that was looked at. Dr. Shilpa Gupta: We didn't look at that specifically, we only compared whether high TMB did better with the immunotherapy or chemotherapy. Dr. Rafeh Naqash: And some of the correlation of this in my mind comes from some data that people have looked at in the lung cancer setting, whether high TMB makes a difference and for example, resected lung cancer patients, which usually gets platinum-based adjuvant therapies. So that's why I was wondering if there's any correlation there. But this is definitely interesting. Now, my next question was going to be in your manuscript you mentioned around 30% of patients had tumor mutational burden more than or equal to ten. Did you identify any other unique characteristics from any other mutational standpoint or a PD-L1 standpoint in the high TMB cohort? Dr. Shilpa Gupta: Yes. So PD-L1 didn't really stand out to be a very steady biomarker in our experience. And this is also what was reflected in the phase three trials like DANUBE where they looked at the durvalumab and tremelimumab, IMvigor130 or KEYNOTE-361. So that was pretty consistent that these studies also showed TMB to be more useful in exploratory analysis. Of course, these patients were not stratified based on that. And we also looked at other emerging biomarkers, for example, F-TBRS and angiogenesis gene expression signatures as well as tGE3. And we need to evaluate them in a separate study to see what pans out. But for now, I think as far as in the real world, we are looking at a lot of genomic testing being done and right now we really don't know how to use that for making treatment decisions, right? PD-L1 has really phased out as of any utility whatsoever. And using TMB; I think in addition to the clinical characteristics, like when possible, we should be offering patients carboplatin. There's no doubt about that for cisplatin ineligible patients. But there's those patients who, if they're refusing chemotherapy and we really can't make a case for giving them single agent immunotherapy, I think TMB can come in handy to justify and make sure that we're not doing them a disservice by not giving carboplatin. And I think future trials need to use this biomarker in a prospective setting to further establish its utility. Dr. Rafeh Naqash: Definitely, I agree it's a case-by-case situation from a patient standpoint to determine what therapy is appropriate for the patient and what is most realistic, what is the expectation that the patient has, from that treatment. Now, from a TMB standpoint, one of the ongoing debates is if it is a binary cut off or whether it could be tertiles for a certain tumor type or quartiles. Was there any subanalysis or any subsequent study that your team would be looking at from a TMB cut off standpoint? Maybe a higher cut off would mean a better outcome and maybe lesser duration of therapy in those patients. Is that somewhat of a consideration? Dr. Shilpa Gupta: Yeah, that's a great question, Rafeh. And I think the reason we stuck to it as a binary end point is because that's the FDA definition, so people don't try to extrapolate based on anything higher or lower. But yeah, that's a great question. And I know in lung cancer they're looking at different ranges. As far as urothelial cancer, we just stuck to the ten mutations per megabase for now. Dr. Rafeh Naqash: Of course. And one of the other interesting things I really like to see in the paper is your figure specifically on the ECOG performance status and how clinical trials sometimes do not include patients on the higher ECOG performance status spectrum. And your study obviously had a good representation on that standpoint. What were some of the findings from the ECOG standpoint that were somewhat different in your cohort than what you would see in clinical trials in general? Dr. Shilpa Gupta: Yes, as we've shown in Figure 5, the ECOG in real world, it was quite an eye opener to see that there was a considerable number of patients who were documented as ECOG performance status three. And if you see the ECOG performance status two bar was around 50% and ECOG performance status one was also lower than what has traditionally been included in the phase three trials. And in the phase three trials, there's hardly any patients with ECOG performance status two compared to what we saw in the real world. And very few patients, in fact, hardly any had ECOG performance status zero in our real world analysis. So clearly the trials need to be more inclusive, as has been the ASCO message all along. And it's always very surprising to see the big gap between the real world and the clinical trial patient population. Dr. Rafeh Naqash: Definitely, I think more and more, especially cooperative group trials that you and many others are leading, are trying to be as inclusive as possible, which is important to get a better understanding of how these therapies do in different patient populations. And one of the questions I wanted to ask you, and I've seen this a few times in different checkpoint therapy treated tumors, is this initial rapid progression in some patients where the chemotherapy arm does better, but the immunotherapy arm kind of falls rapidly and then starts plateauing. In your clinical experience, have you seen that? And if yes, what are the features of some of those patients that have this rapid progression from a clinical and both from a biomarker standpoint? Dr. Shilpa Gupta: That's a great question, Rafeh, and we do see that every now and then, and especially in my experience, we've seen that in women in particular who have bone metastases are really challenging to treat with immunotherapy. And sometimes we find that the disease just rapidly blows through immunotherapy and we really need to do more biomarker work to understand what determines these biomarkers of hyper-progression, so to speak. I know there's a lot of work going on in the field and we are also trying to understand these by serially collecting blood and circulating tumor DNA from our patients during their treatment journey. Dr. Rafeh Naqash: Exactly. Definitely work in progress and another unique patient population where more needs to be done to understand what are the events that lead to these hyper-progression aspects, whether it's in the bone or brain or any other compartment in the body. Well, this has been exciting and interesting, but before we end, we try to know a little bit more about the investigator, the author. So, Shilpa, can you tell us a little bit about your journey in oncology and your journey as a trainee, your journey as faculty, as a clinical trialist, as a successful clinical trialist? And any advice for junior investigators listening to this conversation? Dr. Shilpa Gupta: Yeah, thank you for asking. I think oncology always struck me as a very exciting field back in my residency days, 2005, 2006. And at the time, so much was going on, like just drugs like bevasizumab were just coming around for colorectal cancer and in lung cancer drugs like EGFR inhibitors were coming around. And that kind of really excited me. And talking with my mentor at the time, who was a really well-renowned transplanter, he said to me that if he had to do it all over again, he would love to get into solid tumor oncology with all the excitement that's going on. I was drawn to oncology also because of, not only it's a learning experience every day, but it can be very gratifying to see amazing responses and patients living longer despite having advanced disease, and also provides a lot of challenges every day when every patient is not the same. So I think that was the reason why I was drawn to oncology and provides us an opportunity to really develop new therapies as opposed to some of the other specialties because of how challenging the patient population is. And as far as my journey, you know, I've now been in the US for almost 18 years and have been in a variety of places, and I think it's been a very rewarding journey despite multiple bumps along the way. And I'm really glad to be doing what I'm doing and trying to advance the field, clinical trials, and learning from people around me. Dr. Rafeh Naqash: Thank you so much for giving us a little glimpse into your journey and your experiences. And it's always inspiring to listen to successful investigators and also try to emulate in some ways what you have done and what you've achieved. And thank you again for coming on this podcast. And thank you for choosing JCO Precision Oncology as a destination for your manuscript, and hopefully we'll see more of the same from you and your group in the subsequent years to come and more in this field of biomarkers. Thank you for listening to JCO Precision Oncology Conversations. You can find all our shows, including this one, at ASCO.org/podcasts or wherever you get your podcasts. To stay up to date, be sure to follow and share JCO PO content on Twitter @JCOPO_ASCO. All JCO PO articles and series can be found at ascopubs.org/journal/PO. 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. Guest Bio Shilpa Gupta, MD, is Associate Professor of Medicine at the Cleveland Clinic and GU Medical Oncology Director. Guest disclosures Stock and Other Ownership Interests: Nektar, Moderna Therapeutics Honoraria: Bristol Myers Squibb Consulting or Advisory Role: Gilead Sciences, Guardant Health, AVEO, EMD Serono, Pfizer, Merck, Loxo/Lilly Speakers' Bureau: Bristol Myers Squib
The Top 10 Trending comic books list is back and Comic Tom and his team are here to give you all the details. Livewire is a hot Superman villain again, the Beyonder from Secret Wars could be coming to the MUC, Poison Ivy variants are sprouting up all over the place, Agatha Harkness' keys in Fantastic Four stretch to new heights, BRZRKR is shooting up the competition, Mr. Fixit Hulk is unstoppable, Jason Aaron's Thor remains relevant, Blue Beetle is causing a stir, and Powers of X is back on the list! ❤️ Mystery Mail Call (our comic book subscription service) https://www.comictom101.com/ (US ONLY) ❤️ Subscribe to our YouTube Channel: https://bit.ly/2PfSSSY -------------------------------------------------------------------------------------------------- ✅ Use code "TOM101" for a free week subscription to Key Collector Comics. Available wherever you get apps. ✅Get Key Collector Comics
Gem and Tom are here with another list of the 10 hottest comic book back issues that are making waves with new sales. The RED HULK could be coming to the MUC, iconic Batman covers are hitting the list, Ka-Zar is cool again, Laura Kinney X-23 is spiking, Johnny Blaze Ghost Rider is heating up, Lobo continues to be a DC character on the rise, the Punisher is taking aim at the number one spot, Sentry 1 in a 9.8 remains a tough book to find, Hell Cat is an Avenger to watch for, and Star Trek comics might be out performing Star Wars comics! ❤️ Mystery Mail Call (our comic book subscription service) https://www.comictom101.com/ (US ONLY) ❤️ Follow us on Whatnot!: https://www.whatnot.com/invite/comictom101 ❤️ Subscribe to our YouTube Channel: https://bit.ly/2PfSSSY
This week we will meditate on love. Muc of our time will be spent in the book of 1 John. I encourage you to take the time to read it on your own. Today we will apply Lectio Divina to 1 John 4:20-21. Background music from "Soul Breaker" by Alex Mason and the Minor Emotions. Connect with us: Website: NikkiRach.com Twitter: @MeditationBible Facebook Group: Spiritual Disciplines for Today Email: Nikki.Rach@NikkiRach.com
Liamhás le Micilín Muc ar díol ins na siopaí anois.
Éamonn Ó Sé;Perth. Máirín Ní Ailín;Londain. Pádraig Feirtéar;Marglann an Daingin. Séamus Mac Gearailt;Micilín Muc
This week we will meditate on love. Muc of our time will be spent in the book of 1 John. I encourage you to take the time to read it on your own. Today we will apply Lectio Divina to 1 John 4:18-19. Background music from "Soul Breaker" by Alex Mason and the Minor Emotions. Connect with us: Website: NikkiRach.com Twitter: @MeditationBible Facebook Group: Spiritual Disciplines for Today Email: Nikki.Rach@NikkiRach.com
A little bird hunting and some bear hunting tips before jumping into Muc's elk calling game plan. Muc gives us the run down on how he likes to approach his calling sequence. Elk season is currently underway so any extra little tips during the season to listen to along the way to elk camp could be all you need to get that bull in. Bird Dogs bear hunting tips Elk calling sequence Elk Calling tips *If you enjoyed today's episode please subscribe/follow now to not miss the next episode. I would also appreciate a 5 star review on apple podcasts. Thank you all for listening Wilderness Athlete Promo code: huntinghub Connect with Clint Whitley Instagram @westernhuntinghub Facebook @thewesternhuntinghubpodcast Email: clint.a.whitley@gmail.com Thank you to @ben.j.photo for the use of his elk photo for the podcast cover This podcast is a part of the Waypoint TV Podcast Network. Waypoint is the ultimate outdoor network featuring streaming of full-length fishing and hunting television shows, short films and instructional content, a social media network, Podcast Network. Waypoint is available on Roku, Samsung Smart TV, Amazon Fire TV, Apple TV, Chromecast, Android TV, IoS devices, Android Devices and at www.waypointtv.com all for FREE! Join the Waypoint Army by following them on Instagram at the following accounts @waypointtv @waypointfish @waypointhunt @waypointpodcasts Learn more about your ad choices. Visit megaphone.fm/adchoices
On today's nerdtastically newsworthy episode of #NerdORama we welcome actress Adaku Ononogbo, who joins the program to introduce her character “Fariha” on the new Disney+ Marvel series “Ms. Marvel''!!!
Muc dečka povabi na potep v sanje. Pripoveduje: Majda Grbac. Napisala: Gina Paquet Rück /Ferdinanda Pleško. Posneto v studiih Radiotelevizije Ljubljana 1986.
Guest host Dr. Neeraj Agarwal, of the University of Utah Huntsman Cancer Institute and the ASCO Daily News editor-in-chief, discusses key therapeutic advances in mRCC and mUC, as well as new research that proposes periodic scans to monitor patients with mCSPC for disease progression, with Dr. Jeanny-Aragon-Ching of the Inova Schar Cancer Institute. Transcript: Dr. Neeraj Agarwal: Hello and welcome to the ASCO Daily News podcast. I'm Dr. Neeraj Agarwal, the director of the Genitourinary Oncology Program, a professor of medicine at the University of Utah Huntsman Cancer Institute, and editor-in-chief of the ASCO Daily News. My guest today is Dr. Jeanny Aragon-Ching, who is a medical oncologist and the Clinical Program Director of Genitourinary Cancers at the Inova Schar Cancer Institute in Virginia. Today, we will be discussing key posters in genitourinary (GU) oncology that will be featured at the 2022 ASCO Annual Meeting. Our full disclosures are available in the show notes and disclosures of all guests on the podcast can be found on our transcripts at asco.org/podcast. Jeanny, it is great to have you on the podcast today. Dr. Jeanny Aragon-Ching: Thanks, Neeraj. It's a pleasure for me to be here as well. Dr. Neeraj Agarwal: Jeanny, let's begin with Abstract 4510. This is a trial that represents a growing interest among researchers worldwide in the microbiome and how it is impacted by antibiotics and how it modulates immune checkpoint inhibitor response. Can you tell us about this study? Dr. Jeanny Aragon-Ching: Thanks, Neeraj, I would be happy to. So, the title of the abstract is, “Characterization of the Microbial Resistome in a Prospective Trial of CBM 588 in Metastatic Renal Cell Carcinoma Offers Mechanism for Interplay Between Antibiotic Use and Immune Checkpoint Inhibitor Activity.” So, this is an interesting abstract that originated likely from the observation that getting antibiotics while on checkpoint inhibitors typically results in worse outcomes, perhaps because antibiotics can clear the normal gut flora and thereby increase these pathogenic antibiotic-resistant bacteria. Now, on the other hand, there were some retrospective studies using a live microbial product called CBM 588, which seems to improve outcomes in patients on checkpoint inhibitors and getting antibiotics. So, the idea, therefore, is that shifting the genes encoding antimicrobial resistance could result in a better checkpoint inhibitor response. So, this Abstract 4510 is a small study conducted by Dr. Nazli Dizman and Dr. Sumanta (Monty) Kumar Pal, and colleagues, and enrolled 29 metastatic clear cell RCC patients with intermediate or poorest disease. And they were stratified into receiving either nivolumab or ipilimumab compared to nivo/IPI with CBM 588. Now stool samples were collected at baseline in week 12. And they did this whole metagenome sequencing to analyze a stool microbiome composition, and they also looked at the antibiotic resistance genes for the most common classes of antibiotics. The results showed an astounding improvement in objective responses. So, 58%, for instance, in nivo/IPI and the CBM 588 arm compared to only 20% in the nivo/IPI arm. And it seems like also the antibiotics resistance genes were also decreased in those getting the CBM 588 alongside nivo/IPI. Therefore, responses were improved by shifting the gut microbiome alone. So, these findings were published actually recently by these authors in Nature Medicine. So, in case anyone wants to take a deep dive, it would be a good interesting read for this dataset. Dr. Neeraj Agarwal: Very interesting, indeed. Jeanny, what is the main message here for our colleagues? Dr. Jeanny Aragon-Ching: I think, Neeraj, the key takeaway message is that this is a very provocative proof of concept trial that suggests shifting the gut microbiome has the potential to improve responses to checkpoint inhibitors and outcomes. So, this is a very up-and-coming trial and is seen also across the board in other cancers. Dr. Neeraj Agarwal: Thanks, Jeanny. Moving on to urothelial cancer, there is a poster that I think is a must-see for our colleagues. This is Abstract 4577 titled, “Defining Platinum Ineligible Patients with Metastatic Urothelial Carcinoma.” Dr. Jeanny Aragon-Ching: So, Neeraj, what can you tell us about this abstract? Dr. Neeraj Agarwal: So, over the past few years, there has been a tremendous evolution in the treatment landscape for patients with metastatic urothelial carcinoma. For over 40 years the standard of care for these patients has been cisplatin-based chemotherapy. However, approximately 50% of patients are cisplatin-ineligible, due to underlying comorbidities, and are offered carboplatin as an alternative. So, although the checkpoint inhibitors pembrolizumab and atezolizumab were approved as first-line therapy for these patients in 2017, the U.S. Food and Drug Administration (FDA) has now restricted the use of first-line pembrolizumab to platinum ineligible patients with metastatic urothelial carcinoma. The challenge we face as oncologists since the FDA restriction is the absence of a formal definition of platinum ineligibility and the inclusion of this definition in the guidelines. So, in Abstract 4577, Drs. Shilpa Gupta and Jonathan Rosenberg, along with the team present an updated consensus definition for platinum ineligibility based on an online survey of 60 genitourinary oncologists in the United States. Based on the results from this survey, any patient with metastatic urothelial carcinoma, meeting 1 of the following 5 clinical and or laboratory parameters should be considered platinum ineligible, and these are 1 of the following: an ECOG performance status of 3 or more, creatinine clearance of fewer than 30 mils per minute, or peripheral neuropathy of grade 2 or more, or heart failure class of 3 or more—so, this is NYHA heart failure class of 3 or more—and lastly, the combination of performance status of 2 or more, plus a creatinine clearance of less than 30 mils per minute. Dr. Jeanny Aragon-Ching: Well, this is a timely update, Neeraj. So, what do you think is a key takeaway from this abstract? Dr. Neeraj Agarwal: These criteria based on simple and easily available clinical and or laboratory parameters will now allow us to readily define platinum ineligibility in our patients with metastatic urothelial carcinoma, which is a need in busy clinics, both in academic and community settings. So, I think once published and obviously once endorsed by guidelines, we really would like to be able to use this criterion to quickly define platinum ineligibility in our clinics. Dr. Jeanny Aragon-Ching: Agree. Yeah. Dr. Neeraj Agarwal: So, Jeanny, let me switch the gears. PSMA testing is a hot topic this year. And there is an abstract that could potentially have an impact on future guidelines, and how we will practice further down the road. So, I'm referring to the Abstract 5088 titled, “Predictive Value of Extra Prostatic Disease Detection by Preoperative PSMAPET for Biochemical Recurrence-free Survival in Patients with Otherwise Localized Prostate Cancer and Who are Treated with Radical Prostatectomy.” So, this is a follow-up analysis of a multicenter prospective phase 3 imaging trial. So, could you please tell us more about this abstract where they are using PSMA PET scan in the preoperative localized prostate cancer setting? Dr. Jeanny Aragon-Ching: Absolutely, Neeraj. So, you may recall that the multicenter prospective phase 3 imaging trial that garnered gallium PSMA approval by the FDA was actually based on this study that looked at the intermediate and high-risk patients with prostate cancer undergoing radical prostatectomy and lymph node dissection, and they underwent prior gallium PSMA PET scanning for pelvic nodal metastases prior to surgery. So, this was actually previously reported by Dr. Calais and group. Now they are reporting on Abstract 5088 as a post hoc analysis of the same population and group of patients looking for extraprostatic disease. And the final pathology was also correlated to look at nodal disease in these patients in order to predict biochemical recurrence, so they follow these patients for biochemical recurrence occurrence. So, of the 36% of patients who did undergo radical prostatectomy after they underwent PSMA PET scan, about 41% of them recurred with biochemical recurrence, and 40% of them underwent some kind of salvage therapy or some treatment. What was very interesting was when they looked at the biochemical recurrence-free survival. It was better in those who were PSMA negative, and that recurrence-free survival was easily about 33 months, compared to only about 7.3 months in those who were PSMA-positive scans. Furthermore, the ones who had the longest and the highest biochemical recurrence-free survival, intuitively, were those who were node-negative and PSMA PET-negative, so probably not surprisingly. And that rate was about 46 months—close to 4 years. Whereas those who are node-positive on final pathology and their PSMA PET was also positive, they only had about 3 months of biochemical recurrence-free survival. Dr. Neeraj Agarwal: Very interesting. So, it looks like the PSMA PET scan is predicting biochemical recurrence-free survival in localized prostate cancer settings. So, Jeanny, what is the key takeaway from this trial? Dr. Jeanny Aragon-Ching: I think, Neeraj, the bottom line is that patients with extraprostatic disease that is detected by their preoperative PSMA PET scan does predict strongly a high risk of biochemical relapse, and this can really be an additional tool that clinicians can use to help inform and guide future therapy. Dr. Neeraj Agarwal: Thanks, Jeanny. The research on preoperative PSMA testing and its implications on future treatment strategies in the setting is going to be really interesting to watch in the very near future. Dr. Jeanny Aragon-Ching: Yes, absolutely. I really think we should also discuss Abstract 5072, along those lines, the importance really of radiographic monitoring for disease progression in patients with metastatic hormone-sensitive prostate cancer. Dr. Neeraj Agarwal: Yes, thanks for reminding and this is Abstract 5072. This is a post hoc analysis of the ARCHES trial, titled, “Radiographic Progression in the Absence of PSA Progression in Patients with Metastatic Hormone-sensitive Prostate Cancer.” During the last several years, we have seen many of these agents typically given for gastric resistant prostate cancer moving upfront to the castration-sensitive prostate cancer setting. This is especially true for androgen receptor access targeting agents such as abiraterone, enzalutamide, and apalutamide, all being now approved for patients with metastatic castration-sensitive prostate cancer. What is noteworthy from all these trials, and is reported in Abstract 5072, is the use of imaging studies to evaluate disease progression. So, in Abstract 5072, Dr. Andrew Armstrong and Dr. Arun Azad performed a post hoc analysis of the ARCHES trial to investigate the concordance between radiographic progression and the PSA Progression as defined by PCWG2 criteria, or between radiographic progression and any rise in the PSA above nadir, in patients who were being treated with this novel hormonal therapies, in this case, enzalutamide for metastatic castration sensitive prostate cancer. And as a quick reminder, ARCHES was a phase 3 trial that showed a significant reduction and radiographic progression-free survival and improved overall survival for patients with metastatic castration sensitive prostate cancer treated with enzalutamide plus androgen deprivation therapy (ADT) versus those treated with placebo plus androgen deprivation therapy. So, very interestingly, the findings from this study indicate that 67% of patients on the enzalutamide plus ADT arm did not have [Prostate Cancer Clinical Trials Working Group 2 criteria] PCWG2-defined prostate-specific antigen (PSA) progression at the time of radiographic progression. And discordance was present in the ADT-only arm as well, where they found 42% of patients on the ADT-only arm had radiographic progression but did not have PCWG2-defined PSA progression. Interestingly, this discordance of radiographic disease progression was also seen with any rise in the PSA above nadir. And I personally found this information to be very clinically relevant when we are seeing the majority of patients actually experiencing radiographic disease progression, not experiencing PSA progression at the same time. Dr. Jeanny Aragon-Ching: Yeah, absolutely. I agree with that, Neeraj. So, very interesting data. So, what do you think is the key takeaway message for the clinicians listening to us? Dr. Neeraj Agarwal: I'll make the message very simple. I think the message is that patients with metastatic castration-sensitive prostate cancer need to be monitored for disease progression with periodic scans, and PSA monitoring alone is not sufficient in the majority of these patients. Again, we cannot undervalue the role of periodic imaging studies in these patients so that we can timely diagnose them to have disease progression. Dr. Jeanny Aragon-Ching: I agree with that. Dr. Neeraj Agarwal: Jeanny, the last abstract I would like to mention before we wrap up the podcast is Abstract 4509, the results from the phase1 live SPARC 001 study. So, can you please tell us more about this study titled, “Phase-1 Live SPARC 001: The Study of Belzutifan in Advanced Solid Tumors,” which is an update of the renal cell carcinoma cohort with more than 3 years of total follow up? Dr. Jeanny Aragon-Ching: Thanks, Neeraj. So, while the current therapeutic landscape for patients with metastatic clear cell renal cell carcinoma (RCC) has changed dramatically over the past several years, with significant improvement in patient outcomes. Most patients unfortunately still experience disease progression on current treatments. So, in-depth molecular profiling of clear cell RCC has revealed recurrent loss of function mutations in VHL in actually greater than 90% of patients. So, the VHL protein, as you will recall, is part of the oxygen-sensing pathway, regulating levels of HIF which is hypoxia-inducible factor protein, it's a transcriptional activator that mediates the response to hypoxic conditions. So, HIF-2α is a key oncogenic driver in RCC. So, previous data you may recall from the phase-1 Live SPARC 001 trial was designed to evaluate belzutifan so, this was a novel HIF-2α inhibitor which showed durable anti-tumor activity and acceptable safety profile in patients with metastatic clear cell RCC. So, in Abstract 4509, Drs. Jonasch and Toni Choueiri presented updated results from this trial after more than 3 years of follow-up. Of the 55 patients enrolled 16% of patients remained in treatment. And 62% of patients had discontinued treatment because of, unfortunately, disease progression. The median progression-free survival (PFS) for the total cohort was 14.5 months. And the overall disease control rate was 80%. Forty percent of patients experienced grade 3 treatment-related adverse events with the most frequent ones being anemia and hypoxia. There were no great 4 or 5 treatment-related adverse events. And these results, therefore, show that belzutifan monotherapy continues to show a high rate of disease control and a safety profile in a heavily treated population of patients with metastatic RCC. So, it is great to see that there were no new safety signals. Dr. Neeraj Agarwal: Very nice data indeed. So, Jeanny, what is the key takeaway message here for our listeners? Dr. Jeanny Aragon-Ching: Yeah, I think the message here is that the use of belzutifan monotherapy continues to show efficacy and safety in patients with metastatic clear cell RCC, which have progressed on multiple prior contemporary therapies, and there are phase 3 trials currently underway. Dr. Neeraj Agarwal: Jeanny, any final thoughts before we wrap up the podcast today? Dr. Jeanny Aragon-Ching: Thanks, Neeraj. I think it's a really exciting time to be in genitourinary (GU) oncology, and I'm truly looking forward to seeing some great sessions at the 2022 ASCO Annual Meeting. Dr. Neeraj Agarwal: Thank you, Jeanny, for sharing your insight with us today. It was a great conversation. And thank you to our listeners for joining us today. You will find links to the abstracts discussed today on 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 podcast. 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 Consulting or Advisory Role: Algeta/Bayer, Dendreon, AstraZeneca, Janssen Biotech, Sanofi, EMD Serono, AstraZeneca/MedImmune, Bayer, Merck, Seattle Genetics, Pfizer, Immunomedics, Amgen, AVEO, Pfizer/Myovant, Exelixis Speakers' Bureau: Astellas Pharma, Janssen-Ortho, Bristol-Myers Squibb , Astellas/Seattle Genetics Travel, Accommodations, Expenses: Dendreon, Algeta/Bayer, Bristol Myers Squibb, EMD Serono, Astellas Pharma 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 expressed 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.
This episode is sponsored by Muc™ - it cuts down trees! Actor, musician and comedian Jeremy Limb is this week's special guest as we discuss the Goons' foray into television in the mid-fifties, specifically A Show Called Fred. Although few of the Fred shows survive (and none of its immediate predecessor Idiot Weekly Price 2d) Tyler and Jeremy worked with what they could get and what results is (we hope) an enjoyable and informative conversation about something the like of which which had never been seen on television up to that point, and which shows a clear line to future Python material (coconuts standing in as horses etc). We also celebrate Kenneth Connor, The Alberts and the ubiquitous (for this podcast in any case) Valentine Dyall. Jeremy also talks about his dad who was a notable figure within the BBC Radiophonic Workshop and composer of music for the likes of Box of Delights and Doctor Who. Jeremy is on Twitter @jeremylimb @goonshowpod
© 2020-2025 Ivy Podcast Discovery LLC
