POPULARITY
Categories
Oct 9, 2025 – Gold and silver hit record highs—is this the end or just a pause before another surge? CPM Group's Jeff Christian joins Cris Sheridan to unpack what's driving the rally and whether more gains could be ahead for precious metals investors...
Oct 7, 2025 – What powers our digital world? Journalist Guillaume Pitron reveals the hidden costs—rare metals, energy-guzzling data centers, and global supply chains—behind emails, AI, and streaming in The Dark Cloud. Listen and see tech differently...
Oct 6, 2025 – Are record-high markets making your IRA balloon—and your tax worries grow? Jim Puplava and Crystal Colbert break down how market surges impact IRAs, explore Roth conversions, and share smart tax-saving strategies for retirees...
Oct 3, 2025 – Are the “Mag 7” tech giants losing ground to the “Shiny 7” metals and mining stocks? Financial Sense Newshour's Jim Puplava and Jim Welsh at Macro Tides examine Wall Street's record highs, the broadening bull market...
Oct 3, 2025 – Jordan Roy-Byrne breaks down the historic breakout from a 13-year cup and handle pattern, the crucial signal of gold outperforming the traditional 60/40 portfolio, and the impact of central bank buying and de-dollarization...
Oct 2, 2025 – Laser weapons are moving from science fiction to the front lines, and they could soon be a pillar of national defense. In this eye-opening interview, Applied Energetics CEO Chris Donaghey explains how directed energy weapons are...
October 1, 2025 – Did you know that 99.9% of US businesses are small businesses? In this must-listen interview, Cris Sheridan sits down with Dan Varroney, author of Rethinking Economic Growth , to reveal why small businesses are the true engine of America's economy and how policy needs to change to reflect this reality. They explore how Main Street entrepreneurs drive innovation, face daunting...
Sep 29, 2025 – Retirement is changing, and the old rules may no longer apply. In this timely interview, Jim Puplava of Financial Sense Wealth Management explains the challenges facing today's retirees, from rising inflation and soaring...
Zak Mir talks to Dr Kerim Sener, Managing Director of Ariana Resources, in the wake of the recent summary of projects with drilling planned at Dokwe and the dual listing on the ASX. Highlights: o Ariana commenced trading on the ASX on 10 September 2025, following the completion of a A$11 million IPO, capitalising the Company at c.A$72.5 million. o Flagship >1Moz Dokwe Gold Project in Zimbabwe continues to be advanced through its Definitive Feasibility Study ("DFS"), as additional technical consultancy companies are appointed. o Drilling companies have submitted tenders to undertake a significant new diamond and Reverse Circulation ("RC") drilling programme of c.11,000m at Dokwe; with contracts due to be awarded imminently and drilling to commence in early October. o The drilling programme is designed to substantially increase the current 1.4Moz Resource and 0.8Moz Reserve (as defined in the Pre-feasibility Study - "PFS") at Dokwe, while also providing additional technical data for the DFS. o Gold-silver production continues from the Turkish operations (held 23.5% by Ariana), with production from the Tavşan Mine due to be augmented through its heap-leach imminently. Dr. Kerim Sener, Managing Director, commented: "The successful dual-listing of Ariana on the ASX and its associated capital raising of A$11 million, is a landmark moment since first listing on AIM in 2005. In that time, the Company has evolved from a greenfield exploration company to a gold producer. "The ASX listing provides a powerful platform for us to accelerate our growth strategy, broaden our investor base, and unlock the full potential of our asset portfolio. Central to this is the 100% owned Dokwe Gold Project in Zimbabwe, a highly compelling development opportunity with significant scale, strong economics and exciting upside potential. "With a gold price currently exceeding US$3,600/oz the Company continues to optimise the path forward for the fast-track development of Dokwe, deploying all our skills and capabilities to build up a planned annual gold production of at least 60,000 ounces of gold per annum over a thirteen-year mine life, based on the PFS. With a proven track record of discovery and delivery, Ariana is well positioned to continue building a long-term, sustainable and globally recognised gold company."
Drs. Fahkri and Seshadri discuss recent studies on novel fixed-duration combinations and MRD-guided regimens for CLL. The Sequoia RMD study showed high efficacy with zanubrutinib and venetoclax, achieving a 99% response rate. Similarly, a phase 1 study with sornotoclax and zanubrutinib showed a 96% response rate. The UK FLAIR study demonstrated superior PFS and overall survival with ibrutinib plus venetoclax. The CLL18 trial evaluates MRD-guided vs. fixed-duration treatments with venetoclax and obinutuzumab or pirtobrutinib. Future CLL therapies may increasingly rely on MRD-guided approaches.
Sep 27, 2025 – Gold at record highs, silver edging toward $50, and precious metal mining companies—"the Shiny 7" as we call them—are making major moves. In today's Smart Macro segment of the Financial Sense Newshour, Chris Puplava...
Sep 26, 2025 – If China can build 11 nuclear plants in the time it takes the U.S. to finish one, what does that mean for the future balance of power? Jim Puplava and Cris Sheridan discuss Dan Wang's new book Breakneck: China's Quest...
Sep 26, 2025 – Financial Sense Newshour's Jim Puplava sits down with Dave Keller, President of Sierra Alpha Research, to get an update on his technical outlook for the market, looking at a variety of market metrics, sectors, and companies that...
Sep 26, 2025 – Curious about the future of uranium and nuclear energy markets? Uranium and nuclear analyst Mart Wolbert discusses the recent move by the US to establish a strategic uranium reserve to shift away from Russian dependency...
Sep 25, 2025 – Industrial policy experts Marc Fasteau and Ian Fletcher discuss the big investments the US is making into a variety of industries and companies as part of their “three pillars of US Industrial Policy," which includes currency adjustments...
We connect with Mike Konnert of Vizsla Silver to discuss the latest financing package from Macquarie Bank for a senior secured project finance facility of up to US$220 million to fund the construction and development of the high-grade underground Panuco silver-gold project in Sinaloa, Mexico. We discuss the timing of this as the company continues its test mining work at site. Mike also shares insights into the work happening for the upcoming PFS later this year.
Sep 19, 2025 – Did you know your dentist could be the key to solving your chronic fatigue? In this revealing interview, Jim Puplava sits down with dental sleep expert Dr. Erela Rappaport to unmask the hidden sleep thief: obstructive sleep apnea...
Sep 20, 2025 – Danielle DiMartino Booth joins Financial Sense's Jim Puplava to unpack the Federal Reserve's recent rate cut, revealing why Fed independence is under pressure and how flawed economic data masks true risks...
Sep 19, 2025 – Markets are hitting record highs—and the rally is broadening beyond tech. Join John Roque at 22V Research and Jim Puplava as they unpack what's driving this shift and where the real opportunities lie. From the ongoing bull market...
Sep 19, 2025 – What if the future of global power hinged on an unprecedented economic and technological battle? Join Financial Sense Wealth Management President Jim Puplava as he unravels the escalating tensions between...
Sep 18, 2025 – In a world where blockchain headlines seem quieter than past frenzies, seismic shifts are still reshaping finance behind the scenes. Phil George of EarnOS and FS Insider's Cris Sheridan discuss how stablecoins and tokenization are...
Kinsella on Liberty Podcast, Episode 474. “Where The Common Law Goes Wrong,” 2025 Annual Meeting, Property and Freedom Society, Bodrum, Turkey (Sep. 19, 2025). This will also be podcast later on the Property and Freedom Podcast. Below are my notes, Shownotes provided by Grok, and the transcript. This recording is from my iphone. Professional recording and video will be uploaded later. See also Sebastian Wang, "Stephan Kinsella on the Common Law: Lessons from Bodrum 2025," Libertarian Alliance [UK] Blog (Sep. 19, 2025). Grok Shownotes Show Notes: Stephan Kinsella's “Where the Common Law Goes Wrong” – Property and Freedom Society 2025 Annual Meeting Introduction and Context Stephan Kinsella delivered his talk, “Where the Common Law Goes Wrong,” at the Property and Freedom Society's 2025 Annual Meeting in Bodrum, Turkey, on September 21, 2025. Introduced by Hans-Hermann Hoppe, who shared a brief anecdote about media bias in translating Donald Trump's interactions, Kinsella's presentation revisits themes from his earlier PFS talks in 2012 and 2021, focusing on the interplay between libertarian principles, Roman law, and the common law. Drawing on his recent work, including the Universal Principles of Liberty (co-authored with Alessandro Fusillo, David Dürr, FreeMax, and Patrick Tinsley, under Hoppe's guidance), Kinsella emphasizes the organic development of law and critiques the modern tendency to equate law with legislation. He humorously recounts preparing for the talk with his trainer, who mistook “common law” for “common law marriage,” highlighting the need to clarify legal concepts for a broader audience. Defining Law and Its Evolution Kinsella begins by distinguishing types of law: descriptive (e.g., laws of physics, economics) and normative (e.g., moral codes, legal systems). Legal laws, he argues, blend normative guidance with descriptive consequences, aiming to achieve justice through property rights. He contrasts the modern view of law as statutory decrees—illustrated by tax protesters demanding to “show me the law”—with its historical roots in decentralized systems like Roman law (500 BC–565 AD) and English common law (1066–present). These systems evolved organically through court decisions, with Roman law preserved in Justinian's Corpus Juris Civilis and later rediscovered in Bologna around 1070, influencing European civil codes. Kinsella notes that post-1789 democratic shifts and bureaucratic growth led to an explosion of legislation, overshadowing these private law traditions. Roman Law vs. Common Law The talk explores why Anglo-American scholars, like Hayek and Leoni, often praise the common law's spontaneous order while overlooking Roman law's similar decentralized origins. Kinsella cites Hoppe's observation, from Democracy: The God That Failed, that the common law's non-codified nature may serve lawyers' interests by making it less accessible to laypeople, unlike Europe's clearer civil codes. He refutes the misconception that civil law systems inherently embody totalitarian principles (“all that is not permitted is forbidden”), attributing Europe's socialism to separate legislation, not civil codes. Both Roman and common law, Kinsella argues, offer valuable insights for libertarians, despite the former's neglect in free-market scholarship. Libertarian Law and Rationalism Critique Kinsella critiques the rationalistic tendency among libertarians to design top-down “libertarian law codes,” as exemplified by Rothbard's hope for a comprehensive code in The Ethics of Liberty. Such approaches, he argues, ignore context and the limits of deductive reasoning, echoing Hayek's critique of constructivist rationalism. Law, as a practical response to scarcity and conflict, developed through real-world judicial decisions over centuries. Kinsella suggests that libertarian law should evolve organically, using Roman and common law as starting points, guided by principles like non-aggression but subject to scrutiny f...
Sep 16, 2025 – Learn why a non-recessionary growth slowdown might fuel an ongoing bullish surge in stocks, gold, and crypto. Senior Analyst Mike Singleton of Invictus Research speaks with FS Insider today about emerging tariff-induced...
Sep 12, 2025 – Curious about the current state of the markets, global money supply, and what could be next for the US dollar, gold, and silver? In this in-depth interview, Financial Sense Wealth Management's CIO, Chris Puplava, breaks down...
Sep 11, 2025 – Are we on the brink of a second Cold War turning hot? Geopolitical strategist Christian Takushi reveals the hidden forces reshaping global power—and why the West may be more vulnerable than we think. In this riveting discussion, Takushi delves...
Sep 12, 2025 – With record-breaking highs in the markets and the S&P just points away from Craig Johnson's spot-on 6,600 target, which he forecasted last year, we're diving into what's next for this bull market. Is this just a pit stop, or does the rally...
Host Dr. Shannon Westin and guest Dr. Hani Babiker discuss the JCO article "Tumor Treating Fields With Gemcitabine and Nab-Paclitaxel for Locally Advanced Pancreatic Adenocarcinoma: Randomized, Open-Label, Pivotal Phase III PANOVA-3 Study." TRANSCRIPT TTFields in Locally Advanced Pancreatic Adenocarcinoma Dr. Shannon Westin: Hello everyone, and welcome to another episode of JCO After Hours, the podcast where we get in depth with manuscripts that have been published in the Journal of Clinical Oncology. I am your host, gynecologic oncologist Shannon Westin, social media editor at the JCO, and just excited to be here to learn today about pancreatic cancer. None of our participants have conflicts of interest related to this podcast, and it is my honor to introduce Dr. Hani Babiker. He is an associate professor of medicine, consultant in oncology at the Mayo Clinic in Jacksonville, Florida. Welcome, Dr. Babiker. Dr. Hani Babiker: Hi, Dr. Westin. Thank you for the great opportunity to discuss our trial, and thank you for having me here. I really appreciate it, and I am excited. Dr. Shannon Westin: All right, so are we. So we are going to be talking about “Tumor Treating Fields with Gemcitabine and Nab-Paclitaxel for Locally Advanced Pancreatic Adenocarcinoma: A Randomized, Open-Label, Pivotal Phase III PANOVA-3 Study.” This was simultaneously published and presented in the JCO and at the annual meeting of ASCO on 5/31/2025. So, let's level set. Can you speak to us just a little bit about pancreatic cancer? What is the survival, and what is the typical treatment for locally advanced disease? This gynecologic oncologist has not kept up in this field. Dr. Hani Babiker: Absolutely, Dr. Westin, and thank you for that question. Pancreatic adenocarcinoma is a lethal cancer. When I first started my career, the 5-year survival, per the Surveillance, Epidemiology, and End Results, was at 4.5%. I always, whenever I was giving talks, say that I really hope that I will see it in the double digit. Now, the 5-year survival for all pancreatic adenocarcinoma is 13.3%. And the 5-year survival, and although it is a double digit, I still hope that I will see it in a higher double digit in the future. It is even worse in patients with metastatic cancer, about 3% 5-year survival for metastatic pancreatic cancer. It is a dismal diagnosis. I really hope in the future we will find a better therapeutic approach to this lethal cancer. Dr. Shannon Westin: Yes, I just lost a very dear friend and colleague to this disease, so I completely agree with you. Well, now that we are settled kind of with the basics here, I would love to talk a little bit about kind of the primary piece of this intervention, the Tumor Treating Fields. So, how does this work? And what diseases has it gotten indications in as yet? Dr. Hani Babiker: Absolutely. So, Tumor Treating Fields is alternating frequency electrical fields that have been studied preclinically and shown that it abrogates cancer cell proliferation. Earlier on, we knew that it inhibits polymerization of tubulin, and hence, it affects cancer cells from proliferating. Later, we are learning that there are multiple mechanisms of action. It affects permeability, allowing for better drug delivery. It also inhibits cancer cell proliferation through affecting autophagy mechanisms that pancreatic cancer cells will use for proliferating and becoming more aggressive. There is also some early data preclinically in colorectal cancer cell lines and lung cancer cell lines and in vivo models showing that it potentially could activate the microenvironment to make it more pro-immunogenic. We recently published papers showing that it could also affect the nanomechanical properties of the tumor microenvironment within pancreatic cancer, hinting towards affecting, potentially, the stroma. So, there are multiple mechanisms to Tumor Treating Electric Fields. It is a new, novel therapeutic approach. Sometimes when I speak with my trainees, I say, "Well, we have surgery, we have radiation and chemotherapy, and this is something new." Tumor Treating Fields initially was studied in refractory GBM and got an indication there. Subsequently, frontline treatment of GBM in a randomized clinical trial, and then malignant pleural mesothelioma and non-small cell lung cancer. We have studied it in pancreatic cancer. Dr. Shannon Westin: I don't think I have ever heard it described so perfectly. That was brilliant. So thank you, and I hope everyone listening knows that you just got a masterclass on this mechanism. You know, they dabbled in it a little bit in ovarian cancer and it didn't quite make the grade, so I was a little definitely disappointed. But very excited about the data we're going to talk about today. So let's get into the PANOVA-3 study. Can you highlight the overall design and also the key eligibility criteria that would be helpful for our listeners? Dr. Hani Babiker: Absolutely. So, it started off with preclinical work in pancreatic cancer showing Tumor Treating Fields with chemo abrogate cancer cell perforation. It led to a trial, the PANOVA-2 trial, that was run in Europe that showed efficacy for OS and PFS in patients with locally advanced pancreatic cancer, which included metastatic and locally advanced pancreatic cancer, more so in locally advanced that led to the PANOVA-3 trial, which was an international, global study. This was in more than 190 centers, 20 countries in Latin America, North America, Europe, and Asia. It was a randomized trial. Patients were randomized 1 to 1 to either chemotherapy with gemcitabine plus nab-paclitaxel per drug label. The other arm was with Tumor Treating Fields at 150 kHz for a recommendation for patients to wear it 18 hours per day. The primary end point of the trial was OS, overall survival. The secondary end point included other efficacy landmarks such as local PFS, pain control, quality of life, and safety. And there was a post hoc that looked at distant PFS. Dr. Shannon Westin: That's a pretty common secondary end point in pancreatic studies of looking at the pain-free interval. I thought that was really brilliant because, you know, I think in gyn cancers, we see resolution of symptoms as being a really big deal, but it's not necessarily something that we always look at. So I thought that was really nice that you included that. Okay, talk to us a little bit about the population. So, the population that actually got treated in PANOVA-3 is pretty generalizable to what people are treating in the clinic. Dr. Hani Babiker: So, in pancreatic cancer, unfortunately, most of our patients present, approximately 80%, with metastatic disease. Local is divided to resectable, borderline, and locally advanced. We studied this trial, a randomized trial, in locally advanced and unresectable, which is really an unmet need. Most of our patients with locally advanced and unresectable are grouped up with other trials in the metastatic setting without a focus on locally advanced and unresectable, save for a few trials. This year, a trial that we were looking for for a long time, the LAPLACE trial, unfortunately, that we were very excited about, this is a molecule that targeted connective tissue growth factor, that showed earlier efficacy in a randomized trial, did not meet up the median OS end point. And hence, PANOVA-3 is the first trial in locally advanced and unresectable that did meet its primary end point. So, it's a very unmet need in locally advanced and unresectable. A lot of the times, our patients in clinic are treated with frontline chemotherapy that was studied in metastatic disease and locally advanced and unresectable, which include either FOLFIRINOX, NALIRIFOX, or gemcitabine/abraxane. I do have in my clinic multiple patients that would stay on the regimen for such a long time, and then we would have to devise a mechanism of maintenance, although this is not studied really in details, either with capecitabine or dropping the oxaliplatin to continue FOLFIRI. And then we also approach chemoradiotherapy. So the trial was in a disease in pancreatic cancer that really is an unmet need. So the inclusion criteria included a patient with locally advanced and unresectable. These were done at multiple centers. Most of them academic centers were discussed at the tumor board, and if it's unresectable, they will be meeting specific metrics of appropriate liver function tests, kidney function tests, and blood counts. We excluded patients that obviously had, given that these are electric fields, patients that have, for example, stimulators or pacemakers, knowing that this could potentially affect some of these devices. But for the most part, it was locally advanced and unresectable patients with a very good performance status and good counts. Dr. Shannon Westin: That's great. I think everyone's excited to hear about the primary outcome of overall survival. What did you find, and how does it compare to some of the recent trials? Dr. Hani Babiker: We're very excited that it did meet its primary end point of median overall survival. It was very exciting knowing that a lot of us were disappointed a little bit of some of the trials that were presented at ASCO GI, such as the LAPLACE trial that I alluded to. Just before the presentation, the PRODIGE 29 trial that is in locally advanced and unresectable that randomized patients with locally advanced disease to either FOLFIRINOX or single-agent gemcitabine, allowing for a crossover, although it did meet its primary end point of PFS, there was no overall survival benefit. So that kind of got us a little bit disappointed, but having the PANOVA-3 trial being positive in median OS got us all excited. In addition, the 12-year overall survival rate was increased in both the intention-to-treat and modified intention-to-treat. The modified intention-to-treat were patients that have had at least one cycle of therapy with TTFields daily and/or one cycle with chemotherapy, which was gemcitabine plus nab-paclitaxel. There was a trend to improvement in PFS and local PFS, although that did not have statistical significance, but the 12-year PFS rate in both the intention-to-treat and modified intention-to-treat was significant. For me, as one of the investigators, that told me that there might be a specific biomarker that would tell me that patients could respond greater than others, more exceptional than others, given that 12-month PFS rate was improved. On a post hoc analysis, the distant PFS was improved with the intervention of Tumor Treating Fields with gemcitabine plus nab-paclitaxel. In addition, there was an improvement in global health status and quality of life in addition to pain-free survival, which is a strong hurdle in our patients with pancreatic adenocarcinoma that most present with significant abdominal pain. Dr. Shannon Westin: One of the other questions that I think has come up is around central review. So did you all use central review in this study? Dr. Hani Babiker: Most of the centers were academic centers. These were discussed in tumor boards, which included radiation oncologists and surgeons. I wanted to point out that it's very important to note that the primary end point was overall survival. So the primary end point was not PFS. Hence, the central review would help us, for example, with elaborating and making sure patients were actually locally advanced disease, but in a setting where the primary end point is overall survival, that was the key point of the clinical trial. This trial was discussed at academic centers, and all included tumor boards to decide if patients were locally advanced or not. In the trial, there was a good proportion of patients, or percentage, that had a CA 19-9 more than 1000. That could indicate that potentially there are a fraction of patients that actually had metastatic disease, micrometastatic disease. So that could hint towards why the median OS was slightly lower then in both arms when compared to, for example, the trial that was presented at ASCO GI, the LAPLACE trial. However, having said that, we were very excited about the trial. It was the first positive trial in locally advanced and unresectable to meet median OS survival. Dr. Shannon Westin: It's so awesome. So congratulations. Okay, so let's talk a little bit about your very detailed secondary end points because you had a lot of really prudent choices there. So anything that was interesting or informative in those end points? Dr. Hani Babiker: One major hurdle back we have for most of our patients with pancreatic adenocarcinoma, like I mentioned earlier, is pain. We try to approach it, obviously, with narcotics. If it doesn't work, we try to do celiac axis block interventionally, and that sometimes is successful and sometimes is not. So actually, to see the pain-free survival end point to be met was very exciting for us. And as for me, as a scientist that studies TTFields in clinic and lab as also to develop a mechanism and understanding really how that works. That was very important for us that in addition to chemotherapy, it improved pain-free survival or deterioration of pain. And most importantly, our patients with pancreatic cancer, this disease is very aggressive. It affects quality of life of patients. Patients feel fatigued, tired. It's a procoagulant tumor that causes clots and strokes, etcetera, marantic endocarditis. And one big problem we deal with when we're seeing patients in clinic is obviously that quality of life. Although data have shown with treatment, with frontline regimens, that quality of life improves with treatment and chemotherapy, it's actually great to see that that improvement happens early in addition to Tumor Treating Fields. The other interesting point was that it was not only pain and quality of life, but also digestive symptoms that are improved with this intervention, knowing that a lot of our patients do have pancreatic cancer, pancreatic exocrine insufficiency that affect also with digestion, and a lot of our patients have abdominal pain after eating and diarrhea. So it was interesting to see that also improved with the intervention. Dr. Shannon Westin: You have touched a little bit on some of the adverse events, kind of with the TT mechanisms, but I'd love to hear a little bit more detail around adverse events in general in this study, as well as specific AEs related to the Tumor Treating Fields. Dr. Hani Babiker: Absolutely. So when we compared both arms, there was a similar toxicity related to the regimen, mostly with chemotherapy, but in specifically to Tumor Treating Fields, there was a rash, and that included dermatitis and rash. Most of the side effects were grade 1 and grade 2. Grade 3 toxicities related to skin was less than 10%, approximately 7% to 8%, and hence did not affect many patients. But it was something to note, and it's something that in the future, when we develop a mechanism of treating patients to note early. We in our clinic have learned to treat patients in the clinical trial early with topical steroids to each patient, of shifting the arrays to mitigate some toxicity and rash. We do advise our patients in hot areas, we keep them aware that sweating, for example, can lead to higher conductivity of electrical fields with a predisposition for rash. So if there's an opportunity to stay in a little bit of a cold area, make sure that the arrays are shifted, use topical steroids early. If it's a significant rash, to hold treatment for at least 48 hours and speak to the investigators. And through these mechanisms, we have learned that we were able to mitigate the rash quite a bit. Dr. Shannon Westin: That's awesome. Thank you so much. Yeah, I'm, it's summer right now, and I think- I'm in Texas, you're in Florida, like we know. Okay, so I guess, again, you have been kind of touching on this, but I would love to know, like if in the quality-of-life assessments or if just in your discussions with patients, like how easy is this to use? How easy is the Tumor Treating Fields device to use, and what do patients really think? Dr. Hani Babiker: Absolutely. We have learned that whenever we speak with patients, it's always good to discuss with them briefly the science of it. A lot of patients would want to know if it's interventional, is that something that goes, is delivered percutaneously or not, and we explain that these are delivered through arrays that are through the skin. We always touch base with them about a lot of question I get about mechanism of action and then about compliance. So I think one important thing to note is that compliance with the use of the device is a lot of the question we'll get quite a bit. Patients know there's going to take an effort from them, and some of my patients enjoyed it because they felt like they also are fighting the disease by wearing the device. I have learned very quickly that having a team, surrounded by a team that knew how to mitigate some of the side effects and knew how to explain how to use the device helped quite a bit. And this included some of our nurses and our nurse practitioners and our clinical research coordinators who've done a wonderful job of showing these arrays actually to patients before they start on the trial, look at it, know how it works. The other point to know is that the sponsor provided Device Support Specialist, we call them DSS, they have been instrumental in helping us, helping the patients know how to use the device, how to use the generator, how to change the batteries, and that helped us conduct the trials and enroll very well. I would envision in the future with education and relying on the Device Support Specialist and having a team that knows how to use the device and mitigate some of the side effects will go a long way for patients to learn about this treatment. Many of the times our patients said while they are on the clinical trial felt like they are also being part of this team in applying the device and fighting the cancer. Dr. Shannon Westin: That's awesome. Well, I guess the bottom line. Is it ready for prime time? Is this something you are going to use for your patients in the clinic? Dr. Hani Babiker: Absolutely. In a disease that has poor prognosis, and we are trying our best to find new treatments to fight this cancer and treatment modalities, presenting patients with all the treatment options that are out there would be recommended. It's what I would do it for in my clinic. And you know, it's funny that I am mentioning that right now. I had a patient who was seen internationally asking about the trial and the device and had locally advanced and unresectable before they start frontline treatment. I do think that there is going to be an educational piece. Obviously, this is not a pill, it's not an intravenous chemotherapy that we're very well and accustomed to. And some of us in academic centers know it very well. I usually joke that whenever I am talking about it in pancreatic cancer, if there is a radiation oncologist in the room, they will be like, "Yeah, we know all about it. We have been treating patients with GBM over there." So a lot of the times, when we first went to trial, if I had any questions, I would call them and ask them. So from their perspective, they, because they use it as a standard of care in treatment of GBM, they develop significant expertise in it. I think in the GI world, specifically and with oncologists that treat pancreatic cancer and specifically oncologists in the community, learning about the device and how to use it, how to recommend it, how to mitigate side effects, will be hopefully for prime time in the future. Dr. Shannon Westin: That's great. Sounds like some real educational opportunities there. Well, this has been awesome. Thank you so much, Dr. Babiker. I mean, I learned a ton, and I wish that we could find a way to use this in gynecologic cancers, but really, really just want to commend you on the design of the trial and the success in this really devastating disease. So again, this was "Tumor Treating Fields with Gemcitabine and Nab-Paclitaxel for Locally Advanced Pancreatic Adenocarcinoma: A Randomized, Open-Label, Pivotal Phase III PANOVA-3 Study." And as always, I am your host, Shannon Westin. Please go check out our other offerings wherever you get your podcasts and have an awesome day. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Dr. Babiker Disclosures Consulting or Advisory Role: Endocyte, Celgene, Idera, Myovant Sciences, Novocure, Ipsen, Caris MPI, Incyte, Guardant Health Speakers' Bureau: Guardant Health Research Funding: Spirita Oncology, Novocure, AstraZeneca, JSI, Incyte, Qurient, HiFiBiO Therapeutics, Revolution Health Care, Elevation Oncology, Dragonfly Therapeutics, Zelbio, BMS, Mirati Therapeutics, Strategia
Welcome to Day 2 of the Financial Planner Life Golf Day – where birdies, bogeys, and brilliant business insights go hand in hand.You can watch this episode on youtube or spotify! here This round sees Michael Yuille CFP™ (aka Mr #ChickenTuesday) and Sam Oakes take on Carla Brown (President of the PFS) and Guy Skinner (Citygate Financial Planning) in a best-of-seven match play showdown — with caddies, clubs, and competitive spirit fully loaded.What starts as a light-hearted game quickly turns into a meaningful conversation about building a career in financial planning, winning business, and doing the right thing — both on and off the course.
Sep 9, 2025 – Is the US dollar nearing a historic turning point? Join Cris Sheridan and market strategist Marc Chandler for an unfiltered, must-hear discussion—where currencies, commodities, and global power collide...
September 8, 2025 – Think you know who really benefits from today's tax laws? In this eye-opening episode, Jim Puplava and renowned tax expert Dan Pilla pull back the curtain on the truth behind the headlines. Together, they break down the latest...
JCO fellow Dr. Ece Cali speaks with JCO Associate Editor Dr. Thomas E. Stinchcombe to discuss the JCO article "Phase 2 Dose-Randomized Study of Sunvozertinib in Platinum-Pretreated Non-Small-Cell Lung Cancer with Epidermal Growth Factor Receptor Exon 20 Insertion Mutations (WU-KONG1B)", that was simultaneously released at the IASLC 2025 World Conference on Lung Cancer. TRANSCRIPT Dr. Ece Cali: Hello, and welcome to our series where we cover some of the top JCO papers published simultaneously with their abstract presentation at this year's most important oncology meetings. I am your host, Dr. Ece Cali, JCO editorial fellow, and I am joined by Dr. Tom Stinchcombe, JCO associate editor, to discuss the Journal of Clinical Oncology article and 2025 World Conference on Lung Cancer abstract presentation, “Phase II Dose-Randomized Study of Sunvozertinib in Platinum-Pretreated Non–Small Cell Lung Cancer With EGFR Exon 20 Insertion Mutations.” The WU-KONG1B trial is a multinational, phase II study that investigated the efficacy and safety of different doses of sunvozertinib in patients with metastatic non-small cell lung cancer and EGFR exon 20 insertion mutations after progression on platinum based chemotherapy. Tom, before we dive into the results, could you walk us through the rationale for this study, and how does it fit into the current treatment options for patients with EGFR exon 20 insertion? Dr. Tom Stinchcombe: Thank you, Dr. Cali. I think the clinical context is always important. We have known that EGFR exon 20 insertions exist and that they are resistant to our currently available EGFR tyrosine kinase inhibitors, and I think there have been attempts in the past to develop a tyrosine kinase inhibitor, but there is a very narrow therapeutic window between the dose you need to inhibit the EGFR mutation in the cancer and the EGFR receptor on normal tissues, most notably the mucosa, the gut, and the skin. And so, our previous attempts have failed largely because the dose required was not tolerable for patients and they could not really stay on the drug for a long time or they were not very active. And so, I think there was a real desire to develop an EGFR tyrosine kinase inhibitor, and then, historically, the standard had been a platinum based doublet as the standard of care. And more recently, platinum based doublet with amivantamab has proven to be superior to platinum based chemotherapy alone. I think the context is also important that amivantamab is not necessarily available in all the countries, and so, there are patients who do not have access to amivantamab. Going to the rationale, I think that this drug had shown preliminary promise of having activity but without that being encumbered by those EGFR wild type toxicities, and, therefore, it was really explored in this larger study. Dr. Ece Cali: And what are some key findings from this trial? Dr. Tom Stinchcombe: So, I think that we should look at the study design. It is a little quirky, for lack of a better term, in that there is a randomization to 200 versus 300 mg, and then, there was a nonrandomized cohort of 300 mg. So, when you look at the study, if you are a purist, you will just look at the randomized patients. If you are sort of an aggregator, you look at all patients. So, it shows reporting on three cohorts, but I think the key findings are that the 200 mg and the 300 mg treatments had similar toxicities in terms of response rate, duration of response, and progression free survival. And as you know going through the review, there was a lot of queries from the reviewers as to which would be the preferred dose, and to me, I think this really illustrates a dose finding component to a trial design because there is a lot of debate about what the minimal effective dose is or the optimal dose. And in this case, having the two dose cohorts did provide us some valuable efficacy and toxicity information. And then, when I look at the study, I want to make sure it reflects my patient population, and about a quarter of patients had brain metastases, and about 15% had previous amivantamab, and about 5% to 10% had another EGFR tyrosine kinase inhibitor. Dr. Ece Cali: And what is the objective response rate and the duration of response? These are pretty good numbers for this patient population. Dr. Tom Stinchcombe: In the 200 mg cohort, it was about 46%. The duration of response was around 11 months, and the PFS was around 8 months. The 300 mg cohort was 46%, duration of response 9.8, and the median PFS is 6.9 months, and I think that this is greater activity than we have seen with our previous attempts at EGFR tyrosine kinase inhibitors. Dr. Ece Cali: And based on these data, FDA granted accelerated approval for sunvozertinib very recently at 200 mg once daily dosing in this setting. So, that is a major step forward for our patients. Dr. Stinchcombe, how does this impact your clinical practice, and what side effects should oncologists be watching for if they prescribe this medication? Dr. Tom Stinchcombe: So, I think it was very interesting that they chose the 200 mg dose, which I think was more tolerable, and when we kind of look at this, there still was a rate of diarrhea, all grade, rash, paronychia, which are the EGFR related toxicities. There can be some decreased appetite, stomatitis, and then, it can lead to some lab abnormalities, like increased CPK and creatinine that physicians have to be aware of. You know, how it will affect my practice is that all these patients had received a platinum based chemotherapy as the first line therapy. I think that this would become my preferred second line therapy for patients outside the context of a trial because of the activity and the tolerability. Dr. Ece Cali: And lastly, several other tyrosine kinase inhibitors are being evaluated for EGFR exon 20 insertion, including in the frontline setting. So, what are some of the outstanding questions in this space, and what data should our listeners keep an eye on moving forward? Dr. Tom Stinchcombe: I think you are right that now, there is going to be another EGFR tyrosine kinase that may become available in the next year, and there is another drug, furmonertinib, that is being investigated. I think, for the clinical question, is, well, can we move these into the first line setting? And actually, the development path has two ways of doing this. There is EGFR tyrosine kinase compared to platinum based chemotherapy, and then, platinum based chemotherapy with an EGFR tyrosine kinase versus platinum based chemotherapy, and both have their merits and strengths. And so, I think it is going to be very interesting as we see if those first line trials, one, can they be demonstrated to be superior to platinum based chemotherapy, and then by what magnitude and what the side effects are. But I think we are hoping that in the next couple of years, we will have an additional first line option for our patients. Dr. Ece Cali: Yeah, it is always great to have more options for our patients. Thank you, Dr. Stinchcombe, for speaking about the JCO article, “Phase II Dose-Randomized Study of Sunvozertinib in Platinum-Pretreated Non-Small Cell Lung Cancer With EGFR Exon 20 Insertion Mutations.” Join us again for the latest JCO simultaneous publications. Please take a moment to rate, review, and subscribe to all ASCO podcast shows at asco.org/podcasts. Until then, enjoy the rest of World Lung Conference. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.
Dr. Pedro Barata and Dr. Rana McKay discuss the integration of innovative advances in molecular imaging and therapeutics to personalize treatment for patients with renal cell and urothelial carcinomas. TRANSCRIPT Dr. Pedro Barata: Hello, I'm Dr. Pedro Barata, your guest host of By the Book, a podcast series featuring insightful conversations between authors and editors of the ASCO Educational Book. I'm a medical oncologist at University Hospitals Seidman Cancer Center and an associate professor of medicine at Case Western Reserve University in Cleveland, Ohio. I'm also an associate editor of the ASCO Educational Book. Now, we all know the field of genitourinary cancers (GU) is evolving quite rapidly, and we have new innovations in molecular imaging as well as targeted therapeutics. Today's episode will be exploring novel approaches that are transforming the management of renal cell and urothelial carcinomas and also their potential to offer a more personalized treatment to patients. For that, joining for today's discussion is Dr. Rana McKay, a GU medical oncologist and professor at University of California San Diego. Dr. McKay will discuss her recently published article titled, “Emerging Paradigms in Genitourinary Cancers: Integrating Molecular Imaging, Hypoxia-Inducible Factor-Targeted Therapies, and Antibody-Drug Conjugates in Renal Cell and Urothelial Carcinomas.” Our full disclosures are available in the transcript of this episode. And with that, Rana McKay, great to have you on the podcast today. Dr. Rana McKay: Oh, thank you so much, Dr. Barata. It's really wonderful to be here with you. So, thanks for hosting. Dr. Pedro Barata: No, thanks for taking the time, and I'm looking forward to this conversation. And by the way, let me start by saying congrats on a great article in the Educational Book. Really super helpful paper. I'm recommending it to a lot of the residents and fellows at my own institution. I would like to first ask you to kind of give our listeners some context of how novel approaches in the molecular imaging as well as targeted therapeutics are actually changing the way we're managing patients with GU, but specifically with renal cell carcinoma and urothelial carcinoma. So, what are the areas you would call out as like being big areas for innovation in this context, and why are they important? Dr. Rana McKay: Very good question. And I think this is really what this article highlights. It highlights where are we going from an imaging diagnostics standpoint? Where are we going from a therapeutic standpoint? And I think if we have to step back, from the standpoint of diagnostics, we've seen PET imaging really transform diagnostics in prostate cancer with the advent of PSMA PET imaging, and now PSMA PET imaging is used as a biomarker for selection for theranostics therapy. And so, we're starting to see that enter into the RCC landscape, enter into the urothelial cancer landscape to a lesser extent. And I think it's going to potentially be transformative as these tools get more refined. I think when we think about therapeutics, what's been transformative most recently in the renal cell carcinoma landscape has been the advent of HIF2α inhibition to improve outcomes for patients. And we have seen the approval of belzutifan most recently that has reshaped the landscape. And now there's other HIF2α inhibitors that are being developed that are going to be further important as they get refined. And lastly, I think when we think about urothelial carcinoma, the greatest transformation to treatment in that context has been the displacement of cisplatin and platinum-based chemotherapy as a frontline standard with the combination of enfortumab vedotin plus pembrolizumab. And we've seen antibody-drug conjugates really reshape treatment and tremendously improve outcomes for patients. So, I think those are the three key areas of interest. Dr. Pedro Barata: So with that, let's focus first on the imaging and then we'll get to the therapeutic area. So, we know there's been a paradigm shift, really, when prostate-specific targets emerged as tracers for PET scanning. And so, we now commonly use prostate-specific membrane antigen, or PSMA-based PET scanning, and really transform how we manage prostate cancer. Now, it appears that we're kind of seeing a similar wave in renal cell carcinoma with the new radiotracer against the target carbonic anhydrase IX. What can you tell us about this? And is this going to be available to us anytime soon? And how do you think that might potentially change the way we're managing patients with RCC today? Dr. Rana McKay: First, I'll step back and say that in the context of PSMA PET imaging, we have actually been able to better understand RCC as well. So, we know that PSMA is expressed in the neovasculature of tumors, and it can actually be used to detect renal cell carcinoma tumors. It has a detection rate of about 84% when used for detection. And so, you know, I don't think it's just restricted to carbonic anhydrase IX, but we will talk about that. So, PSMA expressed in the neovasculature has a detection rate of around 84%, particularly if we're looking at clear cell RCC. CAlX is overexpressed in clear cell RCC, and it's actually used in diagnosing renal cell carcinoma when we think of CAlX IHC for diagnosing clear cell RCC. And now there are CAlX PET tracers. The first foray was with the ZIRCON study that was actually an interestingly designed study because it was designed to detect the likelihood of PET imaging to identify clear cell RCC. So, it was actually used in the early diagnostics setting when somebody presents with a renal mass to discriminate that renal mass from a clear cell versus a non-clear cell, and it was a positive study. But when I think about the potential application for these agents, you know, I think about the entire landscape of renal cell carcinoma. This is a disease that we do treat with metastasis-directed therapy. We have certainly seen patients who've undergone metastasectomy have long, durable remissions from such an approach. And I think if we can detect very early onset oligometastatic disease where a metastasis-directed therapy or SABR could be introduced - obviously tested in a trial to demonstrate its efficacy - I think it could potentially be transformative. Dr. Pedro Barata: Wonderful. It's a great summary, and I should highlight you are involved in some of those ongoing studies testing the performance of this specific PET scanning for RCC against conventional imaging, right? And to remind the listeners, thus far, for the most part, we don't really do FDG-PET for RCC. There are some specific cases we do, but in general, they're not a standard scanning. But maybe that will change in the future. Maybe RCC will have their own PSMA-PET. And to your point, there's also emerging data about the role of PSMA-PET scanning in RCC as well, as you very elegantly summarized. Wonderful. So, let me shift gears a little bit because you did, in your introduction, you did highlight a novel MOA that we have in renal cell carcinoma, approved for use, initially for VHL disease, and after that for sporadic clear cell renal cell carcinoma. We're talking about hypoxia-inducible factor 2-alpha inhibitors, or HIF2α inhibitors, such as belzutifan. But there's also others coming up. So, as a way to kind of summarize that, what can you tell us about this breakthrough in terms of therapeutic class, this MOA that got to our toolbox of options for patients with advanced RCC? Tell us a little bit what is being utilized currently in the management of advanced RCC. And where do you see the future going, as far as, is it moving early on? Is it getting monotherapy versus combinations? Maybe other therapies? What are your thoughts about that? What can you tell us about it? Dr. Rana McKay: Belzutifan is a first-in-class HIF2α inhibitor that really established clinical validation for HIF2α as a therapeutic target. When we think about the activity of this agent, the pivotal LITESPARK-005 trial really led to the approval of belzutifan in patients who were really heavily pretreated. It was patients who had received prior IO therapy, patients who had received prior VEGF-targeted therapy. And in the context of this study, we saw a median PFS of 5.6 months, and there did seem to be a tail on the curve when you looked at the 12-month PFS rate with belzutifan. It was 33.7% compared to 17.6% with everolimus. And then when we look at the response rate, it was higher with belzutifan on the order of 22-23%, and very low with everolimus, as we've previously seen. I think one of the Achilles heels of this regimen is the primary PD rate, which was 34% when used in later line. There are multiple studies that are testing belzutifan in combination across the treatment landscape. So, we have LITESPARK-011, which is looking at the combination of belzutifan plus lenvatinib in the second-line setting. We've got the MK-012 [LITESPARK-012] study, which is looking at belzutifan in various combinations in the frontline setting. So there is a combination with IO plus belzutifan. And so this is also being looked at in that context. And then we also have the LITESPARK-022 study, which is looking at pembrolizumab with belzutifan in the adjuvant setting. So there's a series of studies that will be exploring belzutifan really across the treatment landscape. Many of these studies in combination. Additionally, there are other HIF2α inhibitors that are being developed. We have casdatifan, which is another very potent HIF2α inhibitor. You know, I think pharmacologically, these are different agents. There's a different half-life, different dosing. What is going to be the recommended phase 3 dose for both agents, the EPO suppression levels, the degree of EPO suppression, and sustainability of EPO suppression is very different. So, I think we've seen data from casdatifan from the ARC-20 trial from monotherapy with a respectable response rate, over 30%, primary PD rate hovering just around 10%. And then we've also seen data of the combination of casdatifan with cabozantinib as well that were recently presented this year. And that agent is also being tested across the spectrum of RCC. It's being looked at in combination with cabozantinib in the PEAK-1 study, and actually just at the KCRS (Kidney Cancer Research Summit), we saw the unveiling of the eVOLVE-RCC trial, which is going to be looking at a volrustomig, which is a PD-1/CTLA-4 inhibitor plus casdatifan compared to nivo-ipi in the frontline setting. So, we're going to see some competition in this space of the HIF2α inhibitors. I think when we think of mechanism of action in that these are very potent, not a lot of off-target activity, and they target a driver mutation in the disease. And that driver mutation happens very early in the pathogenesis. These are going to be positioned much earlier in the treatment landscape. Dr. Pedro Barata: All these studies, as you're saying, look really promising. And when we talk about them, you mentioned a lot of combinations. And to me, when I think of these agents, it makes a lot of sense to combine because there's not a lot of overlapping toxicities, if you will. But perhaps for some of our listeners, who have not used HIF2α inhibitors in practice yet, and they might be thinking about that, what can you tell us about the safety profile? How do you present it to your patients, and how do you handle things like hypoxia or anemia? How do you walk through the safety profile and tolerability profile of those agents like belzutifan? Dr. Rana McKay: I think these drugs are very different than your traditional TKIs, and they don't cause the classic symptoms that are associated with traditional TKIs that many of us are very familiar with like the rash, hand-foot syndrome, hypertension, diarrhea. And honestly, these are very nuanced symptoms that patients really struggle with the chronicity of being on a chronic daily TKI. The three key side effects that I warn patients about with HIF2α inhibitors are: (1) fatigue; (2) anemia; and (3) hypoxia and dysregulation in the ability to sense oxygen levels. And so, many of these side effects - actually, all of them - are very dose-dependent. They can be very well-managed. So, we can start off with the anemia. I think it's critically important before you even start somebody on belzutifan that you are optimizing their hemoglobin and bone marrow function. Make sure they don't have an underlying iron deficiency anemia. Make sure they don't have B12 or folate deficiency. Check for these parameters. Many patients who have kidney cancer may have some hematuria, other things where there could be some low-level blood loss. So, make sure that those are resolved or you're at least addressing them and supplementing people appropriately. I monitor anemia very closely every 3 to 4 weeks, at least, when people start on these medications. And I do initiate EPO, erythropoietin, should the anemia start to worsen. And I typically use a threshold of around 10g/dL for implementing utilization of an EPO agent, and that's been done very safely in the context of the early studies and phase 3 studies as well. Now, with regards to the hypoxia, I think it's also important to make sure that you're selecting the appropriate individual for this treatment. People who have underlying COPD, or even those individuals who have just a very high burden of disease in their lung, lymphangitic spread, pleural effusions, maybe they're already on oxygen - that's not an ideal candidate for belzutifan. Something that very easily can be done in the clinic before you think about initiating somebody on this treatment, and has certainly been integrated into some of the trials, is just a 6-minute walk test. You know, have the patient walk around the clinic with one of the MAs, one of the nurses, put the O2 sat on [measuring oxygen saturation], make sure they're doing okay. But these side effects, like I said, are very dose-dependent. Typically, if a patient requires, if the symptoms are severe, the therapy can be discontinued and dose reduced. The standing dose is 120 mg daily, and there's two dose reductions to 80 mg and 40 mg should somebody warrant that dose modification. Dr. Pedro Barata: This is relatively new, right? Like, it was not that we're used to checking oxygen levels, right? In general, we're treating these patients, so I certainly think there's a learning curve there, and some of the points that you highlight are truly critical. And I do share many of those as well in our practice. Since I have you, I want to make sure we touch base on antibody-drug conjugates as well. It's also been a hot area, a lot of developments there. When I think of urothelial carcinoma and renal cell carcinoma, I see it a little bit different. I think perhaps in urothelial carcinoma, antibody-drug conjugates, or ADCs, are somewhat established already. You already mentioned enfortumab vedotin. I might ask you to expand a little bit on that. And then in renal cell carcinoma, we have some ADCs as well that you include in your chapter, and that I would like you to tell us what's coming from that perspective. So, tell us a little bit about how do you see ADCs in general for GU tumors, particularly UC and RCC? Tell us a little bit about the complexity or perhaps the challenges you still see. At the same time, tell us about the successes. Dr. Rana McKay: Stepping back, let's just talk about like the principles and design of ADCs. So, most ADCs have three components. There's a monoclonal antibody that typically targets a cell surface antigen, which is conjugated by a linker, which is the second component, to a payload drug. And typically, that payload drug has been chemotherapy, whether it be topoisomerase or whether it be MMAE or other chemotherapeutic. We can start in the RCC space. There's been multiple antibody-drug conjugates that have been tested. There's antibody-drug conjugates to CD70, which is expressed on clear cell RCC. There's been antibody-drug conjugates to ENPP3, which is also expressed on RCC. There's antibody-drug conjugates to CDH6. And they have different payloads, like I said, whether it be topoisomerase I or other microtubule inhibitors. Now, when we think about kidney cancer, we don't treat this disease with chemotherapy. This disease is treated with immunotherapy. It is treated with treatments that target the VEGF pathway and historically has not been sensitive to chemo. So, I think even though the targets have been very exciting, we've seen very underwhelming data regarding activity, and in some context, seen increased toxicity with the ADCs. So, I think we need to tread lightly in the context of the integration and the testing of ADCs in RCC. We just came back from the KCRS meeting, and there was some very intriguing data about a c-Kit ADC that's being developed for chromophobe RCC, which is, you know, a huge unmet need, these variant tumors that really lack appropriate therapeutics. But I just caution us to tread lightly around how can we optimize the payload to make sure that the tumor that we're treating is actually sensitive to the agent that's targeting the cell kill. So, that's a little bit on the ADCs in RCC. I still think we have a long way to go and still in early testing. Now, ADCs for UC are now the standard of care. I think the prototypical agent, enfortumab vedotin, is a nectin-4-directed ADC that's conjugated to an MMAE payload and was the first ADC approved for advanced urothelial, received accelerated approval following the EV-201 trial, which was basically a multicenter, single-arm study that was investigating EV in cisplatin-ineligible patients with advanced urothelial carcinoma, and then ultimately confirmed in the EV-301 study as well. And so, that study ended up demonstrating the support superiority of EV from an overall survival standpoint, even PFS standpoint. Building on that backbone is the EV-302 study, which tested EV in combination with pembrolizumab versus platinum-based chemotherapy in the frontline setting. And that was a pivotal, landmark study that, like I said, has displaced platinum therapy as a frontline treatment for people with advanced urothelial carcinoma. And when we think about that study and the median overall survival and just how far we've come in urothelial cancer, the median OS with EV-pembro from that trial was 31 and a half months. I mean, that's just incredible. The control arm survival was 16 and a half months. The hazard ratio for OS, 0.47. I mean this is why when this data was presented, it was literally a standing ovation that lasted for several minutes because we just haven't seen data that have looked that good. And there are other antibody-drug conjugates that are being tested. We've all been involved in the saga with sacituzumab govitecan, which is a trophoblast cell surface antigen 2 (Trop-2) targeted ADC with a topoisomerase I payload. It was the second ADC to receive approval, but then that approval was subsequently withdrawn when the confirmatory phase 3 was negative, the TROPiCS-04 trial. So, approval was granted based off of the TROPHY-U-01, single-arm, phase 2 study, demonstrating a response rate of around 28% and a PFS of, you know, about 5 and a half months. But then failure to show any benefit from an OS standpoint. And I think there's a lot of controversy in the field around whether this agent still has a role in advanced urothelial carcinoma. And I think particularly for individuals who do not have molecular targets, like they're not HER2-amplified or have HER2-positivity or FGFR or other things like that. Dr. Pedro Barata: Fantastic summary, Rana. You were talking about the EV, and it came to mind that it might not be over, right, for the number of ADCs we use in clinical practice in the near future. I mean, we've seen very promising data for ADC against the HER2, right, and over-expression. It also can create some challenges, right, in the clinics because we're asking to test for HER2 expression. It's almost like, it's not exactly the same to do it in breast cancer, but it looks one more time that we're a little bit behind the breast cancer field in a lot of angles. And also has vedotin as a payload. Of course, I'm referring to disitamab vedotin, and there's very elegant data described by you in your review chapter as well. And it's going to be very interesting to see how we sequence the different ADCs, to your point as well. So, before we wrap it up, I just want to give you the opportunity to tell us if there's any area that we have not touched, any take-home points you'd like to bring up for our listeners before we call it a day. Dr. Rana McKay: Thank you so much. I have to say, you know, I was so excited at ASCO this year looking at the GU program. It was fantastic to see the progress being made, novel therapeutics that really there's a tremendous excitement about, not just in RCC and in UC, but also in prostate cancer, thinking about the integration of therapies, not just for people with refractory disease that, even though our goal is to improve survival, our likelihood of cure is low, but also thinking about how do we integrate these therapies early in the treatment landscape to enhance cure rates for patients, which is just really spectacular. We're seeing many of these agents move into the perioperative setting or in combination with radiation for localized disease. And then the special symposium on biomarkers, I mean, we've really come a long, long way. And I think that we're going to continue to evolve over the next several years. I'm super excited about where the field is going in the treatment of genitourinary malignancies. Dr. Pedro Barata: Oh, absolutely true. And I would say within the Annual Meeting, we have outstanding Educational Sessions. And just a reminder to the listeners that actually that's where the different teams or topics for the Educational Book chapters come from, from actually the educational sessions from ASCO. And your fantastic chapter is an example of that, right, focusing on advanced GU tumors. So, thank you so much, Rana, for taking the time, sharing your insights with us today on the podcast. It was a fantastic conversation as always. Dr. Rana McKay: My pleasure. Thanks so much for having me, Dr. Barata. Dr. Pedro Barata: Of course. And thank you to our listeners for your time today. You will find the link to the article discussed today in the transcript of this episode. I also encourage you to check out the 2025 ASCO Educational Book. You'll find an incredible wealth of information there. It's free, available online, and you'll find, hopefully, super, super important information on the key science and issues that are shaping modern oncology, as we've heard from Dr. McKay and many other outstanding authors. So, thank you, everyone, and I hope to see you soon. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers: Dr. Pedro Barata @PBarataMD Dr. Rana McKay @DrRanaMcKay Follow ASCO on social media: @ASCO on X (formerly Twitter) ASCO on Bluesky ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. Pedro Barata: Stock and Other Ownership Interests: Luminate Medical Honoraria: UroToday Consulting or Advisory Role: Bayer, BMS, Pfizer, EMD Serono, Eisai, Caris Life Sciences, AstraZeneca, Exelixis, AVEO, Merck, Ipson, Astellas Medivation, Novartis, Dendreon Speakers' Bureau: AstraZeneca, Merck, Caris Life Sciences, Bayer, Pfizer/Astellas Research Funding (Inst.): Exelixis, Blue Earth, AVEO, Pfizer, Merck Dr. Rana McKay: Consulting or Advisory Role: Janssen, Novartis, Tempus, Pfizer, Astellas Medivation, Dendreon, Bayer, Sanofi, Vividion, Calithera, Caris Life Sciences, Sorrento Therapeutics, AVEO, Seattle Genetics, Telix, Eli Lilly, Blue Earth Diagnostics, Ambrx, Sumitomo Pharma Oncology, Esiai, NeoMorph, Arcus Biosciences, Daiichi Sankyo, Exelixis, Bristol Myers Squibb, Merck, Astrazeneca, Myovant Research Funding (Inst.): Bayer, Tempus, AstraZeneca, Exelixis, Bristol Myers Squibb, Oncternal Therapeutics, Artera
Sep 25, 2025 – What's really driving gold and silver to record levels, and why are mining stocks suddenly outshining tech giants? In this episode, Jim Puplava sits down with Greg Weldon at Weldon Live to unpack the forces shaking up markets...
Sep 5, 2025 – Gold hit a new record high this week, while silver surged above $40 for the first time in 14 years. Financial Sense's Jim Puplava interviews Mish Schneider, Chief Strategist at MarketGauge, covering the big move in metals and mining stocks, sector...
American Institute of CPAs - Personal Financial Planning (PFP)
When business owners skip exit planning, the fallout can be brutal; value lost, families divided, legacies diminished. But with the right strategy, an exit isn't chaos, it's a launchpad: valuations climb, transitions smooth out, and owners step confidently into their next chapter. In this episode of the AICPA Personal Financial Planning Podcast, host Cary Sinnett welcomes Daniel D. Meiklejohn, JD, CPA, PFS. With his rare combination of legal, tax, and financial planning expertise, Daniel helps business owners turn exits from reactive scrambles into deliberate successes, covering everything from succession and valuation to wealth transfer and legacy planning. Listeners will learn: · The #1 risks owners overlook before selling · Why building the right advisory team changes the outcome · How early planning boosts valuations (and reduces stress) · Where CPA financial planners fit into the exit conversation · Practical ways to help clients start planning today This episode is a must-listen for CPA financial planners who work with business owners—or anyone who wants to sharpen their edge in succession and legacy planning. AICPA Resources: https://www.aicpa-cima.com/cpe-learning/webcast/business-exit-planning https://pfplanning.libsyn.com/business-exit-transitions-for-cpa-financial-planners https://www.aicpa-cima.com/professional-insights/article/pcps-succession-planning-survey
Interview with Rafael Moreno, Managing Director & CEO of Viridis Mining & MineralsRecording date: 2nd Sept 2025Viridis Mining & Minerals (ASX:VMM) is advancing the Colossus ionic clay rare earth project in Brazil's Minas Gerais state, focused on producing high-value rare earth elements neodymium, praseodymium, dysprosium, and terbium (NdPr-DyTb) with very low radioactive content. The project benefits from simple free-dig mining of shallow deposits and straightforward atmospheric-pressure processing, enabled by a unique ionic clay geological formation. These factors contribute to superior economics, with a pre-feasibility study (PFS) estimating a net present value (NPV) of US$1.41 billion and annual operating cash flow around US$200 million at current rare earth prices.Colossus's grades are 4 to 6 times higher than comparable Chinese projects, supporting competitive costs even at lower commodity prices. Regulatory advantages include a radiological exemption from Brazil's nuclear regulator, which keeps environmental approvals at the state level rather than federal, accelerating permitting timelines from years to weeks. The project also features strong environmental credentials, with 100% renewable power, 75% water recycling, and immediate site rehabilitation.Financing momentum is strong, with up to US$30 million committed from leading Brazilian asset managers and ongoing discussions with Brazil's development bank BNDES. Offtake talks span Brazil, Europe, and North America, positioning Colossus as a globally relevant supply source. Near-term milestones include imminent environmental approval, a demonstration plant operational by Q1 2026, mineral resource updates by mid-2026, and a definitive feasibility study (DFS) by June 2026.Led by CEO Rafael Moreno, with deep project execution experience, Viridis is developing Colossus to meet growing global demand driven by electric vehicles, renewable energy, and supply chain diversification concerns. The project's combination of high-grade ore, regulatory fast-tracking, operational simplicity, and sustainable practices create a compelling investment thesis for establishing a non-Chinese rare earth supply focused on permanent magnets, with a potential 60-year mine life ensuring long-term value and market resilience.View Viridis Mining & Minerals' company profile: https://www.cruxinvestor.com/companies/viridis-metals-miningSign up for Crux Investor: https://cruxinvestor.com
Sep 4, 2025 – What happens when politics, technology, and global alliances collide? In this wide-ranging interview, renowned strategist David Woo joins FS Insider's Cris Sheridan to discuss the high-stakes battle for control at the Federal Reserve...
In this episode, guests Jonathan Blattmachr and Martin Shenkman share their thoughts on key OBBBA provisions and the Act's impact on estate and tax planning with host Kristin Yokomoto. Planning considerations include use of non-grantor trusts for charitable planning, basis-focused income tax planning, and more. They will also discuss the benefits of reviewing existing SLATs and other irrevocable trusts, as well as the importance of preparing customized estate plans that address family dynamics to minimize the chances of litigation. Host: Kristin YokomotoGuests: Jonathan G. Blattmachr and Martin M. ShenkmanJonathan G. Blattmachr is the Editor-in-Chief and Co-Founder of Interactive Legal, and Co-Author of Wealth Transfer Planning™. He is a principal in ILS Management, LLC and a retired member of Milbank Tweed Hadley & McCloy LLP in New York, NY and of the Alaska, California and New York Bars. He has written and lectured extensively on estate and trust taxation and charitable giving. Jonathan graduated from Columbia University School of Law cum laude, where he was recognized as a Harlan Fiske Stone Scholar, and received his A.B. degree from Bucknell University, majoring in mathematics. He has served as a lecturer-in-law of the Columbia University School of Law and is an Adjunct Professor of Law at New York University Law School in its Masters in Tax Program (LLM). He is a former chairperson of the Trusts & Estates Law Section of the New York State Bar Association and of several committees of the American Bar Association. Jonathan is a Fellow and a former Regent of the American College of Trust and Estate Counsel and past chair of its Estate and Gift Tax Committee. He is author or co-author of eight books and more than 500 articles on estate planning and tax topics. Martin M. Shenkman, CPA, MBA, PFS, AEP (distinguished), JD, is an attorney in private practice in Fort Lee, New Jersey and New York City. He is the founder of Shenkman Law, a boutique firm focused on the legal needs of high-net-worth individuals, professionals, close business owners, and real estate owners and developers. Martin's practice includes estate and tax planning, planning for closely held businesses, and estate administration. He is the author of 42 books and more than 1,000 articles. Martin is an Editorial Board Member of Trusts & Estates Magazine, CCH (Wolter's Kluwer), and the Matrimonial Strategist. He has previously served on the editorial board of many other tax, estate and real estate publications. Martin earned his Bachelor of Science degree from Wharton School with concentrations in accounting and economics, MBA from the University of Michigan with concentrations in tax and finance, and law degree from Fordham University School of Law. He is admitted to the bar in New York, New Jersey, and Washington, D.C. and is a licensed CPA in New Jersey, Michigan, and New York. Click here to listen to Interactive Legal's 4-Part webinar series on OBBBA - https://interactivelegal.com/big-beautiful-bill/Thank you for listening to Trust Me!Trust Me is Produced by Foley Marra StudiosEdited by Cat Hammons and Todd Gajdusek
What does it take to scale a business without losing your core values? In Episode 163, Vince Virga of PFS shares how conviction, belief, and systems helped him move from chaos to clarity. Joey Brannon and Cameron Earhart unpack the leadership principles behind his journey — from letting go of control to empowering a culture of accountability and growth.This candid conversation offers entrepreneurs practical tools and timeless wisdom for scaling with intention.
Sep 1, 2025 – Discover how retiring business owners can unlock powerful, little-known tax advantages while preserving their legacy in this insightful interview with Lawrence Kaplan of CSG Partners. Financial Sense host Jim Puplava explores how employee...
Aug 22, 2025 – What if China has already secretly surpassed the US as the world's largest holder of gold? In this compelling interview, Jim Puplava is joined by author Dominic Frisby to unravel the forces driving gold's explosive bull market...
Aug 29, 2025 – The Hunt Brothers tried to corner the silver market, driving it up to $50/ounce in the late 70s and early 80s. Now, it's the world's two largest economies trying to corner an increasing list of critical commodities. In this important update...
Aug 28, 2025 – What if the next decade on Wall Street eclipses even the Roaring 1920s? Dr. Ed Yardeni, President and Chief Investment Strategist at Yardeni Research, speaks with FS Insider to give an update on his bullish case for the S&P 500 soaring to...
Aug 27, 2025 – Step inside a world where AI builds worlds, rewrites language, and merges minds—today, not decades from now. In this fascinating conversation, Dr. Alan D. Thompson, renowned AI analyst, breaks down the race toward...
Aug 22, 2025 – This morning in Jackson Hole, Wyoming, Fed Chair Jay Powell stated that monetary policy remains restrictive and that adjustments are likely needed. While a rate cut was already widely anticipated for next month's Fed meeting...
Aug 22, 2025 – Speaking with Financial Sense, Substack powerhouse Doomberg explores how energy has become the decisive factor in the new global power struggle. The conversation highlights China's rapid ascent as the largest producer...
Aug 19, 2025 – Are you prepared for the next move in markets? Find out how global liquidity, tariffs, and fiscal policy are shaping the investment landscape in our exclusive conversation with macro strategist Jonathan Petersen at Variant Perception...
Aug 20, 2025 – Explore the decisive factors in the US-China race for AI supremacy with Woody Preucil of 13D Research and Strategy. While the US leads in chip design and AI models, China's focus on digital infrastructure, 5G, and electricity production...
Join Dave and Bethlie as they continue a study on a few select chapters of the book Ten Pillars of an Awesome Marriage by Charles Shoemaker. PART 2 5. Chapter 5 Conflict Resolution Goal - not to avoid but to handle wisely Illustration of Lady Astor to Winston Churchill - If you were my husband, I would give you poison; if you were my wife, I would take it! P. 85 Swindoll Quote Frequently, marital warfare is in the trenches of belligerence or moodiness. Some battles are night attacks or surprise assaults. Others are cold wars of stoic silence. Cruel methods of torture are also employed—public criticism, fearful threats, intimidation, ugly sarcasm, and hateful remarks designed to put down one's mate. Such tactics are popular . . . but wrong because they are unfair and they never lead to domestic peace.” P. 87 PFS - personal filtering system Age Gender Education Life experiences Culture Temperament Skills Personality Spirituality How do you resolve conflicts Be right with God Be swift to hear and slow to speak Own it when you are wrong Stay focused on issue at hand Face conflicts with a team mindset We not me A marriage struggles when it has two “I”s