Podcasts about PFS

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Latest podcast episodes about PFS

Financial Sense(R) Newshour
Resource Wars and Anti-Fragile Assets: The Macro Butler on the “Banana Republic” Portfolio (Preview)

Financial Sense(R) Newshour

Play Episode Listen Later Dec 23, 2025 3:40


Dec 23, 2025 – What if the world's biggest economic risks—and opportunities—are hiding in plain sight within gold, silver, copper, and critical minerals? In this riveting discussion, Macro Butler's Laurent Lequeu reveals why he believes a new era...

Kinsella On Liberty
KOL480 | The Liberland Constitution and Libertarian Principles (Liberland Prague, 2025)

Kinsella On Liberty

Play Episode Listen Later Dec 21, 2025


Kinsella on Liberty Podcast: Episode 480. This is my talk at the Liberland Constitution Christmas Party Prague 2025, Dec. 19, 2025, based on the article below, which will be included in the book based on the proceedings, First Constitutional Convention of the Free Republic of Liberland, Vít Jedlička, ed. (Dec. 19, 2025; forthcoming). The transcript is also below. Pictures of the event may be be found at Prague 2025: Liberland Constitution Celebration: Photos; also Hoppe, Fusillo, Kinsella Speak at Liberland Constitution Celebration, and Vit's post at Facebook and my facebook post. This audio is from my iphone; video and better audio, and that of other talks, will be released in due course. Related: First Constitutional Convention of the Free Republic of Liberland, Vít Jedlička, ed. (Dec. 19, 2025; forthcoming) (google docs version) Liberland press release Liberland Prepares for a Historic Christmas Celebration and Constitutional Milestone Prague 2025: Liberland Constitution Celebration: Photos Liberland Constitution Christmas Party Prague 2025 Hoppe, Fusillo, Kinsella Speak at Liberland Constitution Celebration Fusillo on the Universal Principles of Liberty and Liberland KOL478 | Haman Nature Hn 185: The Universal Principles of Liberty KOL474 | Where The Common Law Goes Wrong (PFS 2025) Libertarian Nation and Related Projects KOL473 | The Universal Principles of Liberty, with Mark Maresca of The White Pillbox Announcing the Universal Principles of Liberty As noted in Liberland Constitution Christmas Party Prague 2025, despite my frequent criticisms of libertarian activists and activism over the years, and despite my preference for the theoretical side of things, I've been involved in various activist projects for over the years, including helping to draft early versions of the Liberland Constitution. (( The Voluntaryist Constitution. )) I've met Liberland's President, Vít Jedlička, and previous meetings of the Property and Freedom Society. At this year's PFS meeting, he invited me, Alessandro Fusillo, and Hans-Hermann Hoppe to the Liberland meeting in Prague this December. We did attend. It was a marvelous event. Related: My Failed Libertarian Speaking Hiatus; Memories of Mises Institute and Other Events, 1988–20192025 KOL345 | Kinsella's Libertarian “Constitution” or: State Constitutions vs. the Libertarian Private Law Code (PorcFest 2021) KOL359 | State Constitutions vs. the Libertarian Private Law Code (PFS 2021) The Liberland Constitution and Libertarian Principles Stephan Kinsella[*] Remarks prepared for the Liberland Christmas Party and Constitutional Reading, Prague, Dec. 19, 2025   I would like to discuss the issue of “constitutions” and states, and their relation to human freedom. I. Man, Action, and Freedom A. Acting Man A free society has long been the aspiration and dream of liberals of all types, including modern libertarians.[2] What exactly is freedom? To understand this we must understand the nature of human action in the world. Man finds himself in a world of scarcity and hardship, where nothing is guaranteed to him—neither food, nor shelter, nor safety, nor survival. Acting man is aware of his present state and the world around him, of the receding past, and the coming future. He lives in the present, always moving from the immediate past into the coming future. He constantly faces uneasiness in his present condition and about the future anticipates is coming. He is neither omnipotent nor omniscient, as implied by the existence of scarcity and uneasiness, and yet he can act: he can acquire knowledge: he can learn what ends are possible and what scarce means (resources) can cause things to happen. He can use his body, which he directly controls, and he can acquire and possess and use resources in the world by grappling with them using his body, to make things happen—to give rise to a different future than the one he foresees will arrive without his intervention.[3] Knowledge about the world—about causal laws, recipes, facts about the world and his environment, about possible ends he could choose and possible means he could employ—and the availability and employment of causally efficacious resources together make successful human action possible.[4] It makes possible the achievement of ends and the alleviation of felt uneasiness. By using one's mind and body it is possible to succeed, to achieve what Mises would term psychic proft.[5] B. Acting Man in Isolation For Crusoe on his island what concerns acting man is causal and technical knowledge, and knowledge about contingent facts in his world—and the availability of means of action. For him he may face wild animals, injury, lightning and storms and drought and disease, and any number of challenges, but the concept of freedom does not arise. There is only successful action, or profit, and life; and loss and failure, and death. C. Acting Man in Society With the presence of other people man, the social animal, can benefit from the comforts of society, from collective cooperation, from intercourse and trade, from the division and specialization of labor. But there is also the possibility of violent conflict over the use of the scarce means of action that are essential for successful human action. Other people are a potential benefit but also a potential threat. Perhaps because men are social animals have some empathy for others, and perhaps because they understand that violence is not productive, they prefer peaceful and productive use of resources, trade, and cooperation to violence, conflict, and strife.[6] Thus there tends to emerge in society the institution of property rights: widespread social respect for and mutual recognition of property rights rooted in original appropriation and contractual title transfer.[7] Unfortunately, this tends to give rise to an agency—the state—that claims the right to tax and to ultimate decision-making and law-making. As Hoppe notes, Let me begin with the definition of a state. What must an agent be able to do to qualify as a state? This agent must be able to insist that all conflicts among the inhabitants of a given territory be brought to him for ultimate decision-making or be subject to his final review. In particular, this agent must be able to insist that all conflicts involving himself be adjudicated by him or his agent. And implied in the power to exclude all others from acting as ultimate judge, as the second defining characteristic of a state, is the agent's power to tax: to unilaterally determine the price that justice seekers must pay for his services. Based on this definition of a state, it is easy to understand why a desire to control a state might exist. For whoever is a monopolist of final arbitration within a given territory can make laws. And he who can legislate can also tax. Surely, this is an enviable position.[8] The purpose of property rights, of justice, is to permit men to use their own bodies and peacefully acquired (meaning: acquired by original appropriation, which violates no one's rights as the resource is unowned; or by consensual contractual transfer from a previous owner, which also violates no one's rights as the owner consents to the transfer) scarce means without conflict from others. It is so that men are free to use their own bodies or resources without interference from others. II. Freedom in Society Thus terms like freedom and liberty denote a state of affairs where acting man is free to use his body and other scarce resources in the world without physical interference by others—without conflict. It refers to a world where men are free from interference by private trespassers and also free from institutionalized interference by a state. Freedom and liberty just mean the absence of aggression with private property rights. Ideally, a free society means having either no state at all or a minimal state (minarchy) restricted to preventing aggression defined in terms of property rights,[9] and in a society with a largely libertarian ethos and minimal private crime. In such a society there is widespread liberty because there is little private crime and little to no institutionalize crime. A. Freedom and State Aggression But we live in a world governed by non-minimal states. They control most habitable territory on the earth. They compel membership and payment of taxes and monopolize their services, outlawing competitors. By legislative decree, these states prohibit not only acts that are malum in se but acts that are merely malum prohibitum. Although the justification for the agency that polices crime is to reduce aggression by private trespassers, with the state there is more private crime than there would be otherwise, because states are necessarily inefficient an also because they criminalize non-criminal actions.[10] All states are, in fact, criminal (and even minimal states would be criminal, even if they managed to ever emerge); all states engage in institutionalized aggression against private property rights. As Hoppe notes: socialism, by no means an invention of nineteenth century Marxism but much older, must be conceptualized as an institutionalized interference with or aggression against private property and private property claims. Capitalism, on the other hand, is a social system based on the explicit recognition of private property and of nonaggressive, contractual exchanges between private property owners. Implied in this remark, as will become clear in the course of this treatise, is the belief that there must then exist varying types and degrees of socialism and capitalism, i.e., varying degrees to which private property rights are respected or ignored. Societies are not simply capitalist or socialist. Indeed, all existing societies are socialist to some extent. … Next to the concept of action, property is the most basic category in the social sciences.

Financial Sense(R) Newshour
Jim Welsh on Bullish Seasonality, Bifurcated Commodities, and America's Affordability Squeeze

Financial Sense(R) Newshour

Play Episode Listen Later Dec 20, 2025 25:36


Dec 19, 2025 – Will the Santa Claus rally deliver a year-end gift for investors, or are we in for a bumpy ride? Market strategist Jim Welsh at Macro Tides joins Jim Puplava to dissect the latest market congestion, the explosive breakout in silver, and...

Financial Sense(R) Newshour
Why Everything Costs More: Mike Green on Monopoly Dominance in the US (Preview)

Financial Sense(R) Newshour

Play Episode Listen Later Dec 19, 2025 2:02


Dec 18, 2025 – Are record-high markets masking an affordability crisis in America's real economy? Join renowned strategist Michael Green, well-known author of the popular Yes, I Give a Fig newsletter as he reveals why the disconnect between...

Financial Sense(R) Newshour
Silver at $100? 'Second Greatest Breakout in History' Just Getting Started, Says Jordan Roy-Byrne

Financial Sense(R) Newshour

Play Episode Listen Later Dec 19, 2025 36:16


Dec 19, 2025 – Is the historic surge in silver signaling a generational shift in the financial landscape? In this detailed discussion, Jim Puplava interviews precious metals analyst Jordan Roy-Byrne. They dissect the technical and...

Financial Sense(R) Newshour
The New Commodity Supercycle: Energy, AI, and the Race for Industrial Dominance

Financial Sense(R) Newshour

Play Episode Listen Later Dec 19, 2025 35:12


Dec 19, 2025 – The next great global conflict isn't over land, but the critical metals and resources that power our modern-day world. In today's Big Picture edition of the Financial Sense Newshour, Jim Puplava dives into the escalating resource war...

The KE Report
Snowline Gold - Advancing Valley: From PEA to Pre-Feasibility Study

The KE Report

Play Episode Listen Later Dec 18, 2025 19:48


In this KE Report company update, we reconnect with Scott Berdahl, President & CEO of Snowline Gold, for a detailed discussion on the company's transition from a strong PEA into a newly commenced Pre-Feasibility Study (PFS) at the flagship Valley Gold Deposit in Yukon. This conversation focuses on what changes investors could see moving from the PEA to the PFS, how recent drilling may impact the resource and mine plan, and the extensive engineering and de-risking work already underway. Scott also outlines what drill results remain pending from Valley and regional targets, Snowline's broader exploration strategy alongside development, and why advancing Valley remains the core value driver for shareholders. If you have any follow up questions for Scott please email me at Fleck@kereport.com.   Click here to visit the Snowline Gold website to read over the recent news and learn more about the Company - https://snowlinegold.com/   ------------------------ For more market commentary & interview summaries, subscribe to our Substacks: The KE Report: https://kereport.substack.com/ Shad's resource market commentary: https://excelsiorprosperity.substack.com/ Investment disclaimer: This content is for informational and educational purposes only and does not constitute investment advice, an offer, or a solicitation to buy or sell any security. Investing in equities and commodities involves risk, including the possible loss of principal. Do your own research and consult a licensed financial advisor before making any investment decisions. Guests and hosts may own shares in companies mentioned.

Financial Sense(R) Newshour
Jeff Christian on Record Highs: Is This the Start of a Metals Supercycle? (Preview)

Financial Sense(R) Newshour

Play Episode Listen Later Dec 17, 2025 2:50


Dec 16, 2025 – FS Insider sits down with Jeff Christian of CPM Group, one of the industry's most respected and accurate precious metals and commodity analysts, for a comprehensive outlook on the metals markets—especially in light of silver...

Mining Stock Daily
Newcore Gold Completes Infill Program, Eyes Upcoming Deep Diamond Drill Results

Mining Stock Daily

Play Episode Listen Later Dec 17, 2025 14:24


Mining Stock Daily discusses the latest developments at Newcore Gold's Enchi Project in Ghana with CEO Luke Alexander. The discussion covers recent drilling results from the Boin gold deposit, the upcoming pre-feasibility study (PFS), financial strategies including warrant exercises, and the exploration potential of the project. The conversation highlights the company's focus on resource expansion and the positive outlook for 2026, driven by strong market conditions and strategic drilling efforts.

Mining Stock Daily
Morning Briefing: Kenorland Announces Maiden Resource for Frotet Proejct

Mining Stock Daily

Play Episode Listen Later Dec 16, 2025 9:05


Kenorland Minerals have reported the maiden inferred mineral resources estimate for the Regnault gold deposit at the Frotet Project in northern Quebec. New drill results this morning from Newcore Gold, Brixton Metals and Onyx Gold. Awale Resources have commenced a new drill program. Magna Mining plan to begin work on a PFS for Crean Hill. This episode of Mining Stock Daily is brought to you by... Revival Gold is one of the largest pure gold mine developer operating in the United States. The Company is advancing the Mercur Gold Project in Utah and mine permitting preparations and ongoing exploration at the Beartrack-Arnett Gold Project located in Idaho. Revival Gold is listed on the TSX Venture Exchange under the ticker symbol “RVG” and trades on the OTCQX Market under the ticker symbol “RVLGF”. Learn more about the company at ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠revival-dash-gold.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Vizsla Silver is focused on becoming one of the world's largest single-asset silver producers through the exploration and development of the 100% owned Panuco-Copala silver-gold district in Sinaloa, Mexico. The company consolidated this historic district in 2019 and has now completed over 325,000 meters of drilling. The company has the world's largest, undeveloped high-grade silver resource. Learn more at⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ ⁠https://vizslasilvercorp.com/⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Equinox has recently completed the business combination with Calibre Mining to create an Americas-focused diversified gold producer with a portfolio of mines in five countries, anchored by two high-profile, long-life Canadian gold mines, Greenstone and Valentine. Learn more about the business and its operations at ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠equinoxgold.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Integra Resources is a growing precious metals producer in the Great Basin of the Western United States. Integra is focused on demonstrating profitability and operational excellence at its principal operating asset, the Florida Canyon Mine, located in Nevada. In addition, Integra is committed to advancing its flagship development-stage heap leach projects: the past producing DeLamar Project located in southwestern Idaho, and the Nevada North Project located in western Nevada. Learn more about the business and their high industry standards over at integraresources.com

Financial Sense(R) Newshour
Bullseye Craig Johnson's 2026 Outlook: Stock Market Reality Check

Financial Sense(R) Newshour

Play Episode Listen Later Dec 13, 2025 24:13


Dec 12, 2025 – Wall Street buzzes with anticipation as Jim Puplava interviews Craig Johnson, Chief Technical Analyst at Piper Sandler, about the market's future. With the S&P 500 nearing Johnson's “bullseye” target and investors hungry for...

Financial Sense(R) Newshour
The Dollar's Tipping Point: Chris Puplava on What's Next for Precious Metals and Asset Allocation

Financial Sense(R) Newshour

Play Episode Listen Later Dec 13, 2025 27:48


Dec 12, 2025 – With silver soaring to multi-year highs and the dollar at a critical turning point, Chris Puplava, CIO at Financial Sense Wealth Management, argues that the next move for the dollar will have significant consequences for precious metals...

Financial Sense(R) Newshour
Bruce Mehlman: Why the 2026 Midterm Math Doesn't Favor Trump

Financial Sense(R) Newshour

Play Episode Listen Later Dec 12, 2025 30:27


Dec 12, 2025 – As midterms approach, Bruce Mehlman and Jim Puplava discuss how presidential approval, inflation, AI, and regulation are shaping up for an interesting political landscape for 2026 with the biggest surprise likely to come from...

Financial Sense(R) Newshour
2026 Outlook: Data Centers, Inflation, and US Growth with ITR Economics (Preview)

Financial Sense(R) Newshour

Play Episode Listen Later Dec 12, 2025 2:34


Dec 11, 2025 – Seeking a rigorous, data-driven perspective on the U.S. economic outlook? Lauren Saidel-Baker of ITR Economics explores the key macroeconomic themes for 2026 including the data center buildout, inflationary headwinds...

The KE Report
Arizona Sonoran Copper – Key Metrics From The Cactus Project PFS, Envisioned Mine Plan, Exploration Update, Permitting, Capital Raise, Pathway To Development

The KE Report

Play Episode Listen Later Dec 12, 2025 25:34


George Ogilvie, President and CEO of Arizona Sonoran Copper (TSX:ASCU – OTCQX:ASCUF), joins us to outline the key metrics from the Pre-Feasibility Study (PFS) on the Cactus Project in Arizona and the envisioned mine plan.  We also get an exploration update, more clarity around the permitting process, discuss the recent capital raise, and review the pathway to production.   PFS Highlights include: Simple open pit / SXEW operation producing approximately 103,000 tonnes (226 million lbs) of estimated average annual copper cathodes over the first 10 years of mining, which would make Cactus the third largest cathode producer in the USA  Industry-leading capital intensity of $10,894 per tonne of copper cathodes produced $574 million of average annual EBITDA1  Strong economics to support the continued development of Cactus with a focus on simplicity and executability of the open pit copper cathode project, on private land in Arizona Cactus Project is well positioned over the 22-year Project Life of Mine (“LoM”) to generate value at a variety of copper prices: Conventional, Cost-effective Mining and Processing: Open-pit, Heap Leach and SXEW Operation with Oxide and Enriched Materials from Cactus and Parks/Salyer open pits over 22 years of processing Cash costs (C1) of $1.34/lb, All in Sustaining Costs (“AISC”) of $1.62/lb and All in Costs (“AIC”)1 of $2.01/lb Initial mineral reserves of 513 million tons at a grade of 0.52% Total Copper in the Proven and Probable category for 5.3 billion pounds of contained copper 65% conversion of leachable M&I mineral resources to mineral reserves, with increased grades reporting to the heap leach pads Significant benefits to the local community and economy of Arizona, including projected creation of an estimated 600+ direct jobs Future mine expansion opportunities outside of the current mineable copper reserves, including late mine life primary sulphides, Cactus East and other exploration targets Final investment decision as early as Q4 2026 with targeted first cathodes in 2029   George reviews how the incorporation of the newer MainSpring area into the larger Parks-Salyer deposit, over the last 2 years has allowed for a shift in strategy from underground mining over to an open-pit mining method.  They are reviewing moving the center of the open pit more towards the high-grade portion of the  Park-Salyer deposit, the infill drilling showed it expanding towards that direction, which presented better economics and a faster payback period, as outlined in the PFS.   George also provides some updates on permitting for the project, and the importance of it being on private land to help expedite the process, and that they should be submitting their applications later this year for administrative acceptance by early 2026, and then approval 6 months later.  This permitting process will time out well with the release of their Bankable Feasibility Study.     Next we discussed the news on December 2nd, which announced that the Company closed its previously announced private placement of common shares of the Company pursuant to which the Company issued, on a “bought deal” basis, 25,746,300 Common Shares, including 3,358,200 Common Shares granted to the underwriters, at a price of $3.35 per Common Share, for aggregate gross proceeds of C$86,250,105.  This gives the company the runway to execute on all coming workstreams heading into the Bankable Feasibility Study and the capital stack coming together for a construction decision late next year.         If you have any follow up questions for George about Arizona Sonoran, then please email us at Fleck@kereport.com  or Shad@kereport.com.   In full disclosure, Shad has a position in Arizona Sonoran Copper at the time of this recording and may chose to buy or sell shares at any time.   Click here to visit the Arizona Sonoran website to read over all the recent news.   For more market commentary & interview summaries, subscribe to our Substacks:   The KE Report: https://kereport.substack.com/ Shad's resource market commentary: https://excelsiorprosperity.substack.com/     Investment disclaimer: This content is for informational and educational purposes only and does not constitute investment advice, an offer, or a solicitation to buy or sell any security. Investing in equities and commodities involves risk, including the possible loss of principal. Do your own research and consult a licensed financial advisor before making any investment decisions. Guests and hosts may own shares in companies mentioned.    

Financial Sense(R) Newshour
David Woo: Fed's Hawkish Cut and the 2026 Big Tech Challenge (Preview)

Financial Sense(R) Newshour

Play Episode Listen Later Dec 11, 2025 2:53


Dec 10, 2025 – Is the AI boom saving the U.S. economy—or setting it up for a crash? FS Insider's Cris Sheridan speaks with David Woo to unpack the Fed's latest “hawkish” rate cut and just how much the US market outlook is riding on continued...

Mining Stock Daily
Morning Briefing: Heliostar's Cerro de Gallo PFS Highlights an NPV of $424M, an IRR of 33.1%

Mining Stock Daily

Play Episode Listen Later Dec 11, 2025 9:52


Heliostar Metals has published its PFS for the Cerro del Gallo Project in Mexico. We have new drill results out from Talon Metals, Sanu Gold, Scottie Resources and Founders Metals. This episode of Mining Stock Daily is brought to you by... Revival Gold is one of the largest pure gold mine developer operating in the United States. The Company is advancing the Mercur Gold Project in Utah and mine permitting preparations and ongoing exploration at the Beartrack-Arnett Gold Project located in Idaho. Revival Gold is listed on the TSX Venture Exchange under the ticker symbol “RVG” and trades on the OTCQX Market under the ticker symbol “RVLGF”. Learn more about the company at ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠revival-dash-gold.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Vizsla Silver is focused on becoming one of the world's largest single-asset silver producers through the exploration and development of the 100% owned Panuco-Copala silver-gold district in Sinaloa, Mexico. The company consolidated this historic district in 2019 and has now completed over 325,000 meters of drilling. The company has the world's largest, undeveloped high-grade silver resource. Learn more at⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ ⁠https://vizslasilvercorp.com/⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠Equinox has recently completed the business combination with Calibre Mining to create an Americas-focused diversified gold producer with a portfolio of mines in five countries, anchored by two high-profile, long-life Canadian gold mines, Greenstone and Valentine. Learn more about the business and its operations at ⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠equinoxgold.com⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠⁠ Integra Resources is a growing precious metals producer in the Great Basin of the Western United States. Integra is focused on demonstrating profitability and operational excellence at its principal operating asset, the Florida Canyon Mine, located in Nevada. In addition, Integra is committed to advancing its flagship development-stage heap leach projects: the past producing DeLamar Project located in southwestern Idaho, and the Nevada North Project located in western Nevada. Learn more about the business and their high industry standards over at integraresources.com

Financial Sense(R) Newshour
Silver Spikes Over $60 on Massive Short Covering Rally. What Next?

Financial Sense(R) Newshour

Play Episode Listen Later Dec 10, 2025 16:24


Dec 9, 2025 – Silver has doubled in price this year, surging from below $30 to a record high above $60. On this episode, FS Insider welcomes precious metals expert Bob Coleman—who accurately predicted a major "short-covering rally" in silver...

Financial Sense(R) Newshour
The Geopolitical Gold Rush: Singapore's Strategic Ascent (Preview)

Financial Sense(R) Newshour

Play Episode Listen Later Dec 10, 2025 1:54


Dec 9, 2025 – Rising geopolitical tensions are pushing global capital and institutions to seek out safe havens. Enter Singapore—a strategically neutral powerhouse—and gold, the world's ultimate safe-haven asset. The intersection of these two forces...

The KE Report
Thesis Gold - Lawyers-Ranch Project PFS Highlights An After-Tax NPV5% of $4.36 Billion and an IRR of 87.8% at $4,100 Gold and $51 Silver

The KE Report

Play Episode Listen Later Dec 10, 2025 17:21


Ewan Webster, President and CEO of Thesis Gold Inc. (TSXV: TAU) (WKN: A3EP87) (OTCQX: THSGF), joins us for a comprehensive overview of the Pre-Feasibility Study (PFS) announced on December 1st, at the combined Lawyers-Ranch Project, in the Toodoggone Mining District of British Columbia.   This Lawyers-Ranch project hosts a resource of 4.7 million gold equivalent ounces, with a substantial silver contribution, but the PFS economics are based solely on the Proven & Probable Reserves of 3.2 Moz AuEq.   PFS highlights are summarized below: Strong Economics at US$2,900 per ounce of gold (oz Au) and US$35 per ounce of silver (oz Ag): Pre-tax: 73.5%, internal rate of return ("IRR") and $3.73 billion net present value at a 5% discount rate ("NPV5%") After-tax: IRR of 54.4% and an NPV5% of $2.37 billion At US$4,100/oz Au and US$51/oz Ag: Pre-tax: 117.4% IRR and $6.86 billion NPV5% After-tax: 87.8% IRR and $4.36 billion NPV5% Strong Early Production: Strong gold-equivalent ("AuEq")* annual production rates for the first three years averaging 266,000 ounces**, and 187,000 ounces** over the Life of Mine. Increased Tonnes Processed, Increased Throughput Rates and Extended Mine Life: Despite the removal of Inferred Resources from the mine plan, total tonnes processed rose by 18% (relative to the 2024 Preliminary Economic Assessment). Process plant throughput increased by 9% to 13,700 tonnes per day (t/d) and the mine life increased to 15-years, based solely on Measured and Indicated Resources. Mineral Reserve: Maiden Mineral Reserve statement with 76.16 million tonnes of ore grading 0.97 g/t Au and 28 g/t Ag for a total AuEq grade of 1.33 g/t. Low All-in Sustaining Costs ("AISC"): Average AISC of US$1,185 per AuEq ounce. Silver: Silver production accounts for approximately 23% of revenue. Quick Payback: The Project offers an after-tax payback period of 1.1 years at US$2,900 Au and US$35 Ag. Capex: Initial capital expenditure is estimated at $736.2 million, with a compelling after-tax NPV5%:initial capital ratio of 3.2:1. The initial capital estimate does not consider a potential revenue of $91.1 million in pre-production revenue from processing stockpiles as part of the initial commissioning and ramp-up plan. Project Upside: Significant project upside exists both in the potential to further optimize engineering design through a Feasibility Study, and in the project-wide exploration potential that remains untapped. The PFS did not include recovery of the crown pillar between the open pit and underground workings. With further study there is an opportunity to increase the mineable ore from underground without impacting the open pits. Inferred mineral resources from both Ranch and Lawyers are not captured within the PFS mine plan. Upgrading the classification of these Inferred ounces through additional drilling presents an opportunity to potentially expand the mineable materials. Numerous early-stage and undrilled targets exist across the entirety of the Lawyers-Ranch tenure, and Thesis is focused on a comprehensive, systems-based approach to unlocking additional exploration potential in an emerging porphyry district.       If you have any questions for Ewan regarding Thesis Gold, then please email them into us at Fleck@kereport.com or Shad@kereport.com.   In full disclosure, Shad is a shareholder of Thesis Gold at the time of this recording and may choose to buy or sell shares at any time.   Click here to follow the latest news from Thesis Gold   For more market commentary & interview summaries, subscribe to our Substacks:   The KE Report: https://kereport.substack.com/ Shad's resource market commentary: https://excelsiorprosperity.substack.com/     Investment disclaimer: This content is for informational and educational purposes only and does not constitute investment advice, an offer, or a solicitation to buy or sell any security. Investing in equities and commodities involves risk, including the possible loss of principal. Do your own research and consult a licensed financial advisor before making any investment decisions. Guests and hosts may own shares in companies mentioned.

Journal of Clinical Oncology (JCO) Podcast
JCO at 2025 ASH: Pirtobrutinib in Untreated CLL

Journal of Clinical Oncology (JCO) Podcast

Play Episode Listen Later Dec 9, 2025 20:17


JCO Editor-in-Chief Dr. Jonathan Friedberg is joined by colleagues Dr. Jennifer Woyach, Dr. Wojciech Jurczak, and Dr. Matthew Davids to discuss simultaneous publications presented at ASH 2025 on pertibrutinib, a new upfront treatment option for patients with chronic lymphocytic leukemia. TRANSCRIPT The disclosures for guests on this podcast can be found in the show notes. Dr. Jonathan Friedberg: I'm Jonathan Friedberg, editor of Journal of Clinical Oncology, and welcome to JCO After Hours, where we are covering two manuscripts that were presented at the American Society of Hematology meeting 2025 in Orlando, Florida. I am delighted to be joined by colleagues on this call to discuss these pivotal manuscripts which cover the topic of pirtobrutinib, a new upfront treatment option for patients with chronic lymphocytic leukemia. I will first just introduce our guests, Dr. Woyach. Dr. Jennifer Woyach: Hi, my name is Jennifer Woyach. I am from the Ohio State University. Dr. Wojciech Jurczak: Hello, I am Wojciech Jurczak, working at the National Research Institute of Oncology in Krakow, Poland. Dr. Matthew Davids: Hi, I am Matthew Davids from Dana-Farber Cancer Institute in Boston. Dr. Jonathan Friedberg: We are going to start by just learning a little bit about these two trials that were both large, randomized phase 3 studies that I think answered some definitive questions. We will start with your study, Jennifer. If you could just describe the design of your study and the patient population. Dr. Jennifer Woyach: Absolutely. So this is the BRUIN CLL-314 study, and this is a phase 3 randomized trial of pirtobrutinib versus ibrutinib in patients with CLL or SLL who had not previously been treated with a covalent BTK inhibitor. The patients were both treatment-naive and relapsed/refractory, about one-third of the patients treatment-naive, the rest relapsed/refractory, and they were stratified based upon 17p deletion and the number of prior lines of therapy. The primary objective was looking at non-inferiority of overall response rate over the entire treated population as well as the relapsed/refractory patient population. Key secondary objectives included progression-free survival in the intention-to-treat and the smaller relapsed/refractory and treatment-naive populations. Dr. Jonathan Friedberg: And just comment a little bit on the risk of the patients. Dr. Jennifer Woyach: This study was fairly typical of this cohort of patients. Within the relapsed/refractory patient population, there was a median of one prior line of therapy in each of the groups, up to nine prior lines of therapy in the patients included on the study. For the overall cohort, about two-thirds of the patients were IGHV unmutated, about 15% had 17p deletion, 30% had TP53 mutations, and about 35% to 40% had a complex karyotype, which is three or more abnormalities. Dr. Jonathan Friedberg: And what were your findings? Dr. Jennifer Woyach: Regarding the primary outcome, which is the focus of the publication, we did find that pirtobrutinib was indeed non-inferior and actually superior to ibrutinib for overall response rate throughout the entire patient population and in both the relapsed/refractory and treatment-naive cohorts. PFS is a little bit immature at this time but is trending towards also being significantly better in pirtobrutinib-treated patients compared with ibrutinib-treated patients. Probably most significantly, we found this to be the case in the treatment-naive cohort where there was a striking trend to an advantage of pirtobrutinib versus ibrutinib. Dr. Jonathan Friedberg: And the follow-up that you have on that progression-free survival? Dr. Jennifer Woyach: So we have about 18 months follow-up on progression-free survival. Dr. Jonathan Friedberg: The second study, Wojciech, can you just go through the design and patient population that you treated? Dr. Wojciech Jurczak: Thank you, Dr. Friedberg, for this question. So the BRUIN CLL-313 study was, in fact, the first phase 3 study with pirtobrutinib in exclusively untreated CLL patients. It was a randomized study where we challenged pirtobrutinib versus bendamustine-rituximab. At the time we designed the protocol, bendamustine-rituximab was an option as a standard of care, and Bruton tyrosine kinase monotherapy was used far more commonly than nowadays. The primary target of the study was progression-free survival. We took all untreated patients except for those with 17p deletions. Therefore, it is a good representation for intermediate risk. We had about 60% of the population, 56 to be precise, which was unmutated, evenly distributed into two treatment arms. 17p deleted cases were excluded, but we had about 7% and 8% of TP53 mutated patients as well as about 11% and 7%, respectively, in the pirtobrutinib and bendamustine-rituximab arm of patients with complex karyotype. The progression-free survival was in favor of pirtobrutinib and was assessed by an independent review committee. What is important is that the progression-free survival of the bendamustine-rituximab arm was actually similar to the other studies addressing the same questions, like the comparison with ibrutinib in the ALLIANCE study or zanubrutinib in the SEQUOIA study. What was different was the hazard ratio. In our study, it was 0.20. It was one of the longest effect sizes noted in the frontline BTK study. It represented an 80% reduction in progression-free survival or death. If we compare it to ibrutinib or zanubrutinib, it was 0.39 and 0.42 respectively. Presumably, this great effect contributed towards a trend of overall survival difference. Although survival data are not mature enough, there is a clear trend represented by three patients we lost in the pirtobrutinib arm versus 10 patients lost in the bendamustine-rituximab arm. This trend in overall survival is becoming statistically significant despite the fact that there was a possibility of crossover, and effectively 52.9 patients, which means 18 out of 34 patients relapsing in the bendamustine-rituximab arm, were treated by pirtobrutinib. Dr. Jonathan Friedberg: I am going to turn it over to Matt. The question is: why study pirtobrutinib in this patient population? And then with these two studies, how do you find the patients that were treated, are they representative of people who you see? And do you see this maybe being approved and more widely available? Dr. Matthew Davids: I think in terms of the first question, why study this in a frontline population, we have seen very impressive data with pirtobrutinib in a very difficult-to-treat population of CLL patients. This was from the original BRUIN phase 1/2 study where most of the patients had at least two or three lines of therapy, often both a covalent BTK inhibitor and the BCL2 inhibitor venetoclax, and yet they were still responding to pirtobrutinib. The drug was also very well tolerated in that early phase experience. And actually, we have seen phase 3 data from the BRUIN 321 study comparing pirtobrutinib to bendamustine and rituximab in a relapse population as well. So I think that really motivated these studies to look at pirtobrutinib as a first therapy. You know, often in other cancers of course, we want to use our best therapy first, and I think these studies are an initial step at looking at that. In terms of the second question around the patient population, these are pretty representative patient populations, I would say, for most frontline CLL studies. We see patients who are a bit younger and fitter than sort of the general population of CLL patients who are treated in clinical practice, and I think that is true here as well. Median age in the sort of mid-60s here is a bit younger than the typical patients we are treating in practice. But that is not different from other CLL frontline studies that we have seen recently, so I think it makes it a little bit easier as we kind of think across studies to feel comfortable that these are relatively similar populations. Dr. Jonathan Friedberg: How do you see this either getting regulatory approval or potentially being used compared to current standard of care options? Dr. Matthew Davids: So my understanding is that both of these trials were designed with registrational intent in the frontline setting, and they are both positive studies. That is certainly very encouraging in terms of the potential for an approval here. We have seen in terms of the FDA recently some concerns around the proportion of patients who are coming from North America, and my understanding is that is relatively low on these two studies. But nonetheless, the datasets are very impressive, and so I think it is certainly supportive of regulatory approval for frontline pirtobrutinib. Dr. Jonathan Friedberg: I will ask Jennifer a question. The control arm in your study was ibrutinib, and I think many in the audience may recognize that newer, second-generation BTK inhibitors like acalabrutinib and zanubrutinib are more frequently used now if monotherapy is decided. How do you respond to that, and how would you put your results in your pirtobrutinib arm in context with what has been observed with those agents? Dr. Jennifer Woyach: Yeah, that is a great question. Even though in the United States we are predominantly using acalabrutinib or zanubrutinib when choosing a monotherapy BTK inhibitor, this is actually not the case throughout the entire world where ibrutinib is still used very frequently. The head-to-head studies of both acalabrutinib and zanubrutinib compared to ibrutinib have shown us pretty well what the safety profile and efficacy profile of the second-generation BTK inhibitors is. So even though we do not have a head-to-head study of acalabrutinib or zanubrutinib versus pirtobrutinib, I think, given the entirety of data that we have with all of the covalent BTK inhibitors, I think we can safely look at the pirtobrutinib arm here, how the ibrutinib arm compares or performs in context with those other clinical trials. And though we really can not say anything about pirtobrutinib versus acalabrutinib or zanubrutinib, I think we can still get a good idea of what might be the clinical scenarios in which you might want to choose pirtobrutinib. Dr. Jonathan Friedberg: And Wojciech, do you agree with that? Obviously, I think you have acknowledged that chemoimmunotherapy is rarely used anymore as part of upfront treatment for CLL. So, I guess a similar question. If you were to put the pirtobrutinib result in your study in context with, I guess, more contemporary type controls, would you agree that it is competitive? Dr. Wojciech Jurczak: Well, I think that that was the last study ever where bendamustine-rituximab was used as a comparator arm. So we should notice that smashing difference. Because if we look at the progression-free survival at two years, we have 93.4% in pirtobrutinib arm versus 70.7% in bendamustine-rituximab arm. Bendamustine-rituximab arm did the same as in the other trials, like ALLIANCE or SEQUOIA. Pirtobrutinib did exceptionally well, as pirto is not just the very best BTK inhibitor overcoming the resistance, but perhaps even more important for the first line, it is very well tolerated and is a very selective drug. Now, if we look at treatment-related adverse events, the discontinuation rate, they were hardly ever seen. If we compared the adverse events in exposure-adjusted incidence, literally all adverse events were two or three times higher in bendamustine-rituximab arm except for the bleeding tendency, which however was predominantly in CTCAE grade 1 and 2 with just 0.7% of grade 3 hemorrhage. Therefore, I think that we should actually put the best and the safest drugs upfront if we may, and pirtobrutinib is, or should be, the first choice if we choose monotherapy. Now, I understand that we are not presenting you the data of pirtobrutinib in combination with anti-CD20 or with BCL2 inhibitors, but that is to come. Dr. Jonathan Friedberg: Matt, how would you envision, were regulatory approval granted and this were an option, using this in the upfront patient population? Is there anybody who you would preferentially use this or start on this treatment? Or would this be something that you would tend to reserve for second line? Dr. Matthew Davids: So I would say that in general for most of my patients who would want to start with a continuous BTK inhibitor, I would still use a covalent BTK inhibitor, and I say that for a couple of reasons despite the very promising data from these studies. The first is that the follow-up for both of these phase 3 trials is still quite short, in the range of a median 18 to 24 months. And we know that CLL is a marathon, not a sprint, and these patients are going to probably be living for a very long time. And we do have much longer follow-up from the covalent BTK inhibitors, median of 10-year follow-up with ibrutinib and five to six years with zanubrutinib and acalabrutinib respectively. And you know, I do not think that the pirtobrutinib is going to fall off a cliff after two years, but on the other hand, I think there is a lot of value to long-term data in this disease, and that is why I think for most of my patients I would stick with covalent BTK inhibitors. But the other important factor that we need to consider is patients who are younger and may have many different CLL treatments over the years. We have to be very careful, I think, about how we sequence these drugs. We know right now that we can start with covalent BTK inhibitors and then subsequently patients will respond well to the non-covalent inhibitor pirtobrutinib in later lines of therapy. But right now we do not have prospective data the other way around. So how will the patients on these studies who progress on pirtobrutinib respond to covalent BTK inhibitors? We do not know yet. There have not been a lot of progression events, which is great, but we would like to see some data in that respect to feel more comfortable with that sequence. Now, I do think that particularly for older patients and those who have significant cardiovascular comorbidities, if they wanted to go on a continuous BTK inhibitor, I do think these data really strongly support using pirtobrutinib as the BTK inhibitor of choice in that population. In particular, the cardiovascular risks with pirtobrutinib seem to be quite low. I was very struck in the comparison with BR that the rate of AFib was equivalent between the two arms of the study. And that is really the first time we have seen that with any of these BTK inhibitors, no elevated risk of AFib in a randomized study. I think that is the population where it will get the most traction first, is the upfront, sort of older patient with significant cardiovascular comorbidities. And as the data from these studies mature, I think that we will start to see more widespread use of pirtobrutinib in the frontline setting. Dr. Jonathan Friedberg: Jennifer, I am just curious if you have any personal experience or heard anecdotally about after progression on pirtobrutinib the use of other BTK inhibitors and whether there is a growing experience there. Dr. Jennifer Woyach: I do not think that there is much clinical experience, you know, as Matt alluded to, it certainly has not been tested yet. There has been some data in relapsed CLL suggesting that in people who have resistance mutations to covalent BTK inhibitors after treatment with pirtobrutinib, sometimes those mutations go away. I think most of us are concerned that they are probably not actually gone but maybe in compartments that we just have not sampled, suggesting that sort of approach where you might sequence a covalent inhibitor after a non-covalent in somebody who had already been resistant probably would not work that well. But, you know, in this setting where people had never been exposed to a covalent BTK inhibitor before, we really have no idea what the resistance patterns are going to be like. We assume they will be the same as what we have seen in relapsed CLL, but I think we just need some longer follow-up to know for sure. Dr. Wojciech Jurczak: If I may confront Dr. Davids about the use of covalent BTK inhibitors upfront, well, I think that we should abandon the idea of using the first and the second and the third generation, at least if we don't have medical lines. If we endlessly block the same pathway, it is not going to be effective. So if pirtobrutinib gets approval in first, second line, we do not necessarily have to use it in the first line. I am not here in a position to defend that we should treat patients with pirtobrutinib upfront and not BCL2 time-limited regimen. However, the way I look at CLL patients when choosing therapy is not just how should I treat them now, but what would be the best regimen in 5, 10 years if I have to re-treat them. And in some instances, the idea may be that in this setting we would like to have a BTK inhibitor upfront to have a BCL2 inhibitor later to make it time-limited. Although I understand and I agree with Matthew that if we have an elderly, fragile population, then the charm of having a drug taken once a day in a tablet with literally few cardiovascular adverse events might be an option. Dr. Jonathan Friedberg: And I will give Matt the last word whether he wants to respond to that, and also just as a forward-looking issue, I know both investigators have implied that there will be future studies looking at combinations with pirtobrutinib, and if you have any sense as to what you would be looking for there. Dr. Matthew Davids: The field really is heading toward time-limited therapy for most patients, I would say. There is a bit of a discrepancy right now in the field between sort of what we are doing in academic practice and what is done sort of more widely in community practice. And so right now we are going to see evolving datasets comparing these approaches. We are already seeing data now from the CLL17 study with ibrutinib comparing continuous to time-limited venetoclax-based therapy, and we are seeing similar efficacy benefits from these time-limited therapies without the need for continuous treatment. And so that is where I think some of the future studies with pirtobrutinib combining it with venetoclax and other partners are so important. Fortunately, several of these studies are already ongoing, including a phase 3 trial called CLL18, which is looking at pirtobrutinib with venetoclax, comparing that to venetoclax and obinutuzumab. So I am optimistic that we are going to be developing these very robust datasets where we can actually use pirtobrutinib in the frontline setting as a time-limited therapy as a component of a multi-drug regimen. So far, those early data are very promising. Dr. Wojciech Jurczak: Perhaps last but not least, in a single center we have treated over 300 patients with pirtobrutinib. So eventually some of them relapsed. And I must say that our experience on BCL2 inhibitors, not just venetoclax but including sonrotoclax, are appealingly good. Therefore, by using pirtobrutinib even earlier, we do not block the efficacy of other compounds. Dr. Jonathan Friedberg: All right. Well, I want to thank all of our speakers. I also want to congratulate our two guests who presented these very influential papers at the ASH Annual Meeting, and chose to publish them in JCO, so we thank you for that, and Dr. Davids for your commentary - really appreciated. That is this episode of JCO After Hours. Thank you for your attention. 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.   Disclosures Dr. Wojciech Jurczak Consulting or Advisory Role: BeiGene, Lilly, Abbvie/Genentech, Takeda, Roche, AstraZeneca Research Funding: Roche, Takeda, Janssen-Cilag, BeiGene, AstraZeneca, Lilly, Abbvie/Genentech Dr. Jennifer Woyach Consulting or Advisory Role: Pharmacyclics, Janssen, AstraZeneca, Beigene, Loxo, Newave Pharmaceutical, Genentech, Abbvie, Merck Research Funding: Company name: Janssen, Schrodinger, beone, Abbvie, Merck, Loxo/Lilly Dr. Matthew Davids Honoraria: Curio Science, Aptitude Health, Bio Ascend, PlatformQ Health, Plexus Consulting or Advisory Role: Genentech, Janssen, Abbvie, AstraZeneca, Adaptive Biotechnologies, Ascentage Pharma, BeiGene, Lilly, Bristol-Myers Squibb, Genmab, Merck, MEI Pharma, Nuvalent, Inc., Galapagos NV, Schroedinger Research Funding: Ascentage Pharma, Novartis, MEI Pharma, AstraZeneca  

Financial Sense(R) Newshour
Beyond Diet: Social Connections and Purpose in Lifespan Extension

Financial Sense(R) Newshour

Play Episode Listen Later Dec 8, 2025 23:05


Dec 8, 2025 – Explore the science of longevity in this compelling discussion between Financial Sense's Jim Puplava and Nick Buettner at Blue Zones. Drawing on extensive research from the world's longest-lived populations, Buettner outlines...

Financial Sense(R) Newshour
Electricity Wars: Ukraine, Data Centers, and Swinging Elections

Financial Sense(R) Newshour

Play Episode Listen Later Dec 6, 2025 46:33


Dec 5, 2025 – What if the future of war, politics, and your electric bill were all connected? In this must-hear conversation, veteran host Jim Puplava sits down with acclaimed energy expert and author Robert Bryce to expose the hidden battle for...

Financial Sense(R) Newshour
Uranium's Next Boom: Woody Preucil on US, Global Push to Nuclear Power (Preview)

Financial Sense(R) Newshour

Play Episode Listen Later Dec 5, 2025 3:17


Dec 2, 2025 – Is uranium the next big investment? Discover why global energy shifts, tech-driven demand, and supply shortages could spark an ongoing uranium bull market. 13D's Woody Preucil discusses the future of nuclear and where...

Financial Sense(R) Newshour
John Roque: Big Tech, Silver's Moonshot, and 2026 Market Setups

Financial Sense(R) Newshour

Play Episode Listen Later Dec 5, 2025 27:15


Dec 5, 2025 – Wondering where the stock market is headed as we wrap up the year—and what could be in store for 2026? Financial Sense's Jim Puplava speaks with veteran market strategist John Roque at 22V Research as they dive into...

Oncology Brothers
FDA Approval of Epcoritamab-Rituximab-Lenalidomide for R/R Follicular Lymphoma – Dr. Gilles Salles

Oncology Brothers

Play Episode Listen Later Dec 4, 2025 21:31


In this episode of The Oncology Brothers, we discussed the recent approval of Epcoritamab for relapsed refractory follicular lymphoma. Joined by Dr. Gilles Salles from Memorial Sloan Kettering, we dived into the EPCOR FL1 study, which highlighted the combination of Epcoritamab with rituximab and lenalidomide, showcasing significant improvements in progression-free survival (PFS) and overall response rates. Key topics included: • The mechanism of action of Epcoritamab as a bispecific antibody targeting CD20 and CD3. • Study design and findings from the EPCOR FL1 trial. • Step-up dosing schedule and its implications for patient management. • Side effects to monitor, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). • The role of minimal residual disease (MRD) and ctDNA in treatment decisions. Join us as we explored the future of treatment options in follicular lymphoma and the potential impact on patient quality of life. Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Don't forget to like, subscribe, and hit the notification bell for more updates on the latest in oncology! #Epcoritamab #FollicularLymphoma #BispecificAntibody #CRS #Immunotherapy #OncologyBrothers #Lymphoma

Intelligent Money Minute
How to Prepare for a Successful Business Exit with Mike Meilinger

Intelligent Money Minute

Play Episode Listen Later Dec 4, 2025 7:28


In this episode of Intelligent Money Minute, Hans Blake, CFA, CPA, sits down with Mike Meilinger, CPA, ABV, CFF, PFS, and managing partner of Meilinger Consulting, on how to guide […] The post How to Prepare for a Successful Business Exit with Mike Meilinger appeared first on Intelligent Investing.

Financial Sense(R) Newshour
Dr. Ed Yardeni: Roaring 2020s Could Drive Both Gold and S&P 500 to 10,000 (Preview)

Financial Sense(R) Newshour

Play Episode Listen Later Dec 3, 2025 3:00


Dec 2, 2025 – Market strategist Dr. Ed Yardeni joins FS Insider's Cris Sheridan to discuss his bullish outlook, including a 10,000 target for the S&P 500 by 2029. Yardeni, known for his “Roaring 2020s” thesis, highlights strong economic and...

The KE Report
Dave Erfle - Silver's $96/oz Technical Target, Thesis Gold's Impressive PFS & M&A Recaps

The KE Report

Play Episode Listen Later Dec 3, 2025 18:43


In this editorial, Dave Erfle, Founder and Editor of the Junior Miner Junky, breaks down the explosive move in silver, now approaching $60/oz, and the technical long-term target of $96/oz. We analyze the macro tailwinds and examine the Pre-Feasibility Study (PFS) from Thesis Gold (TSX-V:TAU). The PFS reveals exceptional economics, with an After-Tax NPV of $2.37 Billion (at base case $2,900 Gold and $35 Silver). Dave also covers the accelerating M&A environment, including the bolt-on acquisition by Montage Gold and the strategic divestment by Endeavour Silver. Key Discussion Points: Silver Price Trajectory: The technical and fundamental case for continued upside, including the long-term $96/oz target and the impact of looming Fed rate cuts. Thesis Gold PFS Analysis: Breakdown of the economics, emphasizing the 23% silver value often ignored by the market. M&A Trends: Examination of the latest merger activity, including the accretive acquisition by Montage Gold and the strategic move by Endeavour Silver to shed non-core assets. Valuation Strategy: Advice on navigating the current market volatility, focusing on buying undervalued juniors and trimming fully valued positions. Click here to visit the Junior Miner Junky website to learn more about Dave's investment letter.   ------------------- For more market commentary & interview summaries, subscribe to our Substacks:  The KE Report: https://kereport.substack.com/  Shad's resource market commentary: https://excelsiorprosperity.substack.com/   Investment disclaimer: This content is for informational and educational purposes only and does not constitute investment advice, an offer, or a solicitation to buy or sell any security. Investing in equities and commodities involves risk, including the possible loss of principal. Do your own research and consult a licensed financial advisor before making any investment decisions. Guests and hosts may own shares in companies mentioned.

Financial Sense(R) Newshour
Year-End Tax Planning: Key Moves to Maximize 2025 Benefits

Financial Sense(R) Newshour

Play Episode Listen Later Dec 2, 2025 19:28


Dec 1, 2025 – As year-end approaches, prioritize Roth conversions before December 31st to capitalize on low tax rates. Complete critical actions like 529 contributions, gifting, RMDs, and charitable distributions by year-end to ensure tax benefits...

Oncology Brothers
FDA Approval of Epcoritamab-Rituximab-Lenalidomide for R/R Follicular Lymphoma – Dr. Gilles Salles

Oncology Brothers

Play Episode Listen Later Dec 1, 2025 21:31


In this episode of The Oncology Brothers, we discussed the recent approval of Epcoritamab for relapsed refractory follicular lymphoma. Joined by Dr. Gilles Salles from Memorial Sloan Kettering, we dived into the EPCOR FL1 study, which highlighted the combination of Epcoritamab with rituximab and lenalidomide, showcasing significant improvements in progression-free survival (PFS) and overall response rates. Key topics included: • The mechanism of action of Epcoritamab as a bispecific antibody targeting CD20 and CD3. • Study design and findings from the EPCOR FL1 trial. • Step-up dosing schedule and its implications for patient management. • Side effects to monitor, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). • The role of minimal residual disease (MRD) and ctDNA in treatment decisions. Join us as we explored the future of treatment options in follicular lymphoma and the potential impact on patient quality of life. Follow us on social media: •⁠  ⁠X/Twitter: https://twitter.com/oncbrothers •⁠  ⁠Instagram: https://www.instagram.com/oncbrothers •⁠  Website: https://oncbrothers.com/ Don't forget to like, subscribe, and hit the notification bell for more updates on the latest in oncology! #Epcoritamab #FollicularLymphoma #BispecificAntibody #CRS #Immunotherapy #OncologyBrothers #Lymphoma

Financial Sense(R) Newshour
Ken Rogoff on “Our Dollar, Your Problem”: Debt, China, and the Dollar's Fragile Reign

Financial Sense(R) Newshour

Play Episode Listen Later Nov 28, 2025 34:08


November 28, 2025 – Is the dollar's reign under threat? Jim Puplava interviews Harvard's Kenneth Rogoff on “Our Dollar, Your Problem,” discussing how US debt, political division, China's yuan, and crypto challenge dollar dominance and why...

Financial Sense(R) Newshour
Dr. Alan D Thompson: AGI by 2026 (Preview)

Financial Sense(R) Newshour

Play Episode Listen Later Nov 27, 2025 3:18


Nov 26, 2025 – Humanoid robots are on the verge of an “iPhone moment”—and the AI revolution is accelerating faster than ever. In this fascinating interview, Cris Sheridan and AI expert Dr. Alan D. Thompson explore how robots are mastering...

Mad Radio
PettyCast: Diving into Maye & Portnoy vs Stephen A & More

Mad Radio

Play Episode Listen Later Nov 25, 2025 19:14


Seth and Sean get petty and listen to others being petty. This week they dive into Cam Newton vs Drake Maye vs Stephen A Smith vs Dave Portnoy. Whew! Kenyon Martin lists all the PFs better than Draymond, Klay Thompson isn't a Ja Morant fan, and Kenzel Kelly yelling to 'free his boy BK' his boy meaning his dad Brian Kelly.

Financial Sense(R) Newshour
Before Disaster Hits: How to Prepare for Emergencies

Financial Sense(R) Newshour

Play Episode Listen Later Nov 22, 2025 16:43


Nov 24, 2025 – Emergencies can happen without warning, making preparation essential. In this episode, Kevin Matsukado, former Head of Safety and Security at Hawaii Pacific University, shares a practical five-step approach to emergency...

Financial Sense(R) Newshour
Mark Mills: AI Most Energy-Hungry Tech Ever Invented – Data Centers, the Grid, and Black Swans

Financial Sense(R) Newshour

Play Episode Listen Later Nov 21, 2025 59:09


Nov 21, 2025 – AI is rapidly transforming the U.S. economy and energy grid. Jim Puplava and Mark Mills discuss the surge in AI data centers, rising energy demand, skilled trade shortages, and how America can lead the global AI race amid major...

Financial Sense(R) Newshour
Ron William: The Gold Bell Has Rung!

Financial Sense(R) Newshour

Play Episode Listen Later Nov 21, 2025 24:26


Nov 21, 2025 – Is gold sending an alarm for the broader outlook? Today, on Financial Sense Newshour, Jim Puplava interviews Ron William on how gold's rally is a “bell ringing” for investors, signaling a generational rotation from equities...

ASCO Daily News
What Frontline Treatment Should Be Used in Advanced Ovarian Cancer?

ASCO Daily News

Play Episode Listen Later Nov 20, 2025 25:46


Dr. Linda Duska and Dr. Kathleen Moore discuss key studies in the evolving controversy over radical upfront surgery versus neoadjuvant chemotherapy in advanced ovarian cancer. TRANSCRIPT Dr. Linda Duska: Hello, and welcome to the ASCO Daily News Podcast. I am your guest host, Dr. Linda Duska. I am a professor of obstetrics and gynecology at the University of Virginia School of Medicine.  On today's episode, we will explore the management of advanced ovarian cancer, specifically with respect to a question that has really stirred some controversy over time, going all the way back more than 20 years: Should we be doing radical upfront surgery in advanced ovarian cancer, or should we be doing neoadjuvant chemotherapy? So, there was a lot of hype about the TRUST study, also called ENGOT ov33/AGO-OVAR OP7, a Phase 3 randomized study that compares upfront surgery with neoadjuvant chemotherapy followed by interval surgery. So, I want to talk about that study today. And joining me for the discussion is Dr. Kathleen Moore, a professor also of obstetrics and gynecology at the University of Oklahoma and the deputy director of the Stephenson Cancer Center, also at the University of Oklahoma Health Sciences.  Dr. Moore, it is so great to be speaking with you today. Thanks for doing this. Dr. Kathleen Moore: Yeah, it's fun to be here. This is going to be fun. Dr. Linda Duska: FYI for our listeners, both of our full disclosures are available in the transcript of this episode.  So let's just jump right in. We already alluded to the fact that the TRUST study addresses a question we have been grappling with in our field. Here's the thing, we have four prior randomized trials on this exact same topic. So, share with me why we needed another one and what maybe was different about this one? Dr. Kathleen Moore: That is, I think, the key question. So we have to level-set kind of our history. Let's start with, why is this even a question? Like, why are we even talking about this today? When we are taking care of a patient with newly diagnosed ovarian cancer, the aim of surgery in advanced ovarian cancer ideally is to prolong a patient's likelihood of disease-free survival, or if you want to use the term "remission," you can use the term "remission." And I think we can all agree that our objective is to improve overall survival in a way that also does not compromise her quality of life through surgical complications, which can have a big effect. The standard for many decades, certainly my entire career, which is now over 20 years, has been to pursue what we call primary cytoreductive surgery, meaning you get a diagnosis and we go right to the operating room with a goal of achieving what we call "no gross residual." That is very different – in the olden days, you would say "optimal" and get down to some predefined small amount of tumor. Now, the goal is you remove everything you can see.  The alternative strategy to that is neoadjuvant chemotherapy followed by interval cytoreductive surgery, and that has been the, quote-unquote, "safer" route because you chemically cytoreduce the cancer, and so, the resulting surgery, I will tell you, is not necessarily easy at all. It can still be very radical surgeries, but they tend to be less radical, less need for bowel resections, splenectomy, radical procedures, and in a short-term look, would be considered safer from a postoperative consideration. Dr. Linda Duska: Well, and also maybe more likely to be successful, right? Because there's less disease, maybe, theoretically. Dr. Kathleen Moore: More likely to be successful in getting to no gross residual. Dr. Linda Duska: Right. Yeah, exactly. Dr. Kathleen Moore: I agree with that. And so, so if the end game, regardless of timing, is you get to no gross residual and you help a patient and there's no difference in overall survival, then it's a no-brainer. We would not be having this conversation. But there remains a question around, while it may be more likely to get to no gross residual, it may be, and I think we can all agree, a less radical, safer surgery, do you lose survival in the long term by this approach? This has become an increasing concern because of the increase in rates of use of neoadjuvant, not only in this country, but abroad. And so, you mentioned the four prior studies. We will not be able to go through them completely. Dr. Linda Duska: Let's talk about the two modern ones, the two from 2020 because neither one of them showed a difference in overall survival, which I think we can agree is, at the end of the day, yes, PFS would be great, but OS is what we're looking for. Dr. Kathleen Moore: OS is definitely what we're looking for. I do think a marked improvement in PFS, like a real prolongation in disease-free survival, for me would be also enough. A modest improvement does not really cut it, but if you are really, really prolonging PFS, you should see that-  Dr. Linda Duska: -manifest in OS. Dr. Kathleen Moore: Yeah, yeah. Okay. So let's talk about the two modern ones. The older ones are EORTC and CHORUS, which I think we've talked about. The two more modern ones are SCORPION and JCOG0602. So, SCORPION was interesting. SCORPION was a very small study, though. So one could say it's underpowered. 170 patients. And they looked at only patients that were incredibly high risk. So, they had to have a Fagotti score, I believe, of over 9, but they were not looking at just low volume disease. Like, those patients were not enrolled in SCORPION. It was patients where you really were questioning, "Should I go to the OR or should I do neoadjuvant? Like, what's the better thing?" It is easy when it's low volume. You're like, "We're going." These were the patients who were like, "Hm, you know, what should I do?" High volume. Patients were young, about 55. The criticism of the older studies, there are many criticisms, but one of them is that, the criticism that is lobbied is that they did not really try. Whatever surgery you got, they did not really try with median operative times of 180 minutes for primary cytoreduction, 120 for neoadjuvant. Like, you and I both know, if you're in a big primary debulking, you're there all day. It's 6 hours. Dr. Linda Duska: Right, and there was no quality control for those studies, either. Dr. Kathleen Moore: No quality control. So, SCORPION, they went 451-minute median for surgery. Like, they really went for it versus four hours and then 253 for the interval, 4 hours. They really went for it on both arms. Complete gross resection was achieved in 50% of the primary cytoreduced. So even though they went for it with these very long surgeries, they only got to the goal half the time. It was almost 80% in the interval group. So they were more successful there. And there was absolutely no difference in PFS or OS. They were right about 15 months PFS, right about 40 months OS.  JCOG0602, of course, done in Japan, a big study, 300 patients, a little bit older population. Surprisingly more stage IV disease in this study than were in SCORPION. SCORPION did not have a lot of stage IV, despite being very bulky tumors. So a third of patients were stage IV. They also had relatively shorter operative times, I would say, 240 minutes for primary, 302 for interval. So still kind of short. Complete gross resection was not achieved very often. 30% of primary cytoreduction. That is not acceptable. Dr. Linda Duska: Well, so let's talk about TRUST. What was different about TRUST? Why was this an important study for us to see? Dr. Kathleen Moore: So the criticism of all of these, and I am not trying to throw shade at anyone, but the criticism of all of these is if you are putting surgery to the test, you are putting the surgeon to the test. And you are assuming that all surgeons are trained equally and are willing to do what it takes to get someone to no gross residual. Dr. Linda Duska: And are in a center that can support the post-op care for those patients. Dr. Kathleen Moore: Which can be ICU care, prolonged time. Absolutely. So when you just open these broadly, you're assuming everyone has the surgical skills and is comfortable doing that and has backup. Everybody has an ICU. Everyone has a blood bank, and you are willing to do that. And that assumption could be wrong. And so what TRUST said is, "Okay, we are only going to open this at centers that have shown they can achieve a certain level of primary cytoreduction to no gross residual disease." And so there was quality criteria. It was based on – it was mostly a European study – so ESGO criteria were used to only allow certified centers to participate. They had to have a surgical volume of over 36 cytoreductive surgeries per year. So you could not be a low volume surgeon. Your complete resection rates that were reported had to be greater than 50% in the upfront setting. I told you on the JCOG, it was 30%. Dr. Linda Duska: Right. So these were the best of the best. This was the best possible surgical situation you could put these patients in, right? Dr. Kathleen Moore: Absolutely. And you support all the things so you could mitigate postoperative complications as well. Dr. Linda Duska: So we are asking the question now again in the ideal situation, right? Dr. Kathleen Moore: Right. Dr. Linda Duska: Which, we can talk about, may or may not be generalizable to real life, but that's a separate issue because we certainly don't have those conditions everywhere where people get cared for with ovarian cancer. But how would you interpret the results of this study? Did it show us anything different? Dr. Kathleen Moore: I am going to say how we should interpret it and then what I am thinking about. It is a negative study. It was designed to show improvement in overall survival in these ideal settings in patients with FIGO stage IIIB and C, they excluded A, these low volume tumors that should absolutely be getting surgery. So FIGO stage IIIB and C and IVA and B that were fit enough to undergo radical surgery randomized to primary cytoreduction or neoadjuvant with interval, and were all given the correct chemo. Dr. Linda Duska: And they were allowed bevacizumab and PARP, also. They could have bevacizumab and PARP. Dr. Kathleen Moore: They were allowed bevacizumab and PARP. Not many of them got PARP, but it was distributed equally, so that would not be a confounder. And so that was important. Overall survival is the endpoint. It was a big study. You know, it was almost 600 patients. So appropriately powered. So let's look at what they reported. When they looked at the patients who were enrolled, this is a large study, almost 600 patients, 345 in the primary cytoreductive arm and 343 in the neoadjuvant arm. Complete resection in these patients was 70% in the primary cytoreductive arm and 85% in the neoadjuvant arm. So in both arms, it was very high. So your selection of site and surgeon worked. You got people to their optimal outcome. So that is very different than any other study that has been reported to date. But what we saw when we looked at overall survival was no statistical difference. The median was, and I know we do not like to talk about medians, but the median in the primary cytoreductive arm was 54 months versus 48 months in the neoadjuvant arm with a hazard ratio of 0.89 and, of course, the confidence interval crossed one. So this is not statistically significant. And that was the primary endpoint. Dr. Linda Duska: I know you are getting to this. They did look at PFS, and that was statistically significant, but to your point about what are we looking for for a reasonable PFS difference? It was about two months difference. When I think about this study, and I know you are coming to this, what I thought was most interesting about this trial, besides the fact that the OS, the primary endpoint was negative, was the subgroup analyses that they did. And, of course, these are hypothesis-generating only. But if you look at, for example, specifically only the stage III group, that group did seem to potentially, again, hypothesis generating, but they did seem to benefit from upfront surgery.  And then one other thing that I want to touch on before we run out of time is, do we think it matters if the patient is BRCA germline positive? Do we think it matters if there is something in particular about that patient from a biomarker standpoint that is different? I am hopeful that more data will be coming out of this study that will help inform this. Of course, unpowered, hypothesis-generating only, but it's just really interesting. What do you think of their subset analysis? Dr. Kathleen Moore: Yeah, I think the subsets are what we are going to be talking about, but we have to emphasize that this was a negative trial as designed. Dr. Linda Duska: Absolutely. Yes. Dr. Kathleen Moore: So we cannot be apologists and be like, "But this or that." It was a negative trial as designed. Now, I am a human and a clinician, and I want what is best for my patients. So I am going to, like, go down the path of subset analyses. So if you look at the stage III tumors that got complete cytoreduction, which was 70% of the cases, your PFS was almost 28 months versus 21.8 months. Dr. Linda Duska: Yes, it becomes more significant. Dr. Kathleen Moore: Yeah, that hazard ratio is 0.69. Again, it is a subset. So even though the P value here is statistically significant, it actually should not have a P value because it is an exploratory analysis. So we have to be very careful. But the hazard ratio is 0.69. So the hypothesis is in this setting, if you're stage III and you go for it and you get someone to no gross residual versus an interval cytoreduction, you could potentially have a 31% reduction in the rate of progression for that patient who got primary cytoreduction. And you see a similar trend in the stage III patients, if you look at overall survival, although the post-progression survival is so long, it's a little bit narrow of a margin.  But I do think there are some nuggets here that, one of our colleagues who is really one of the experts in surgical studies, Dr. Mario Leitao, posted this on X, and I think it really resonated after this because we were all saying, "But what about the subsets?" He is like, "It's a negative study." But at the end of the day, you are going to sit with your patient. The patient should be seen by a GYN oncologist or surgical oncologist with specialty in cytoreduction and a medical oncologist, you know, if that person does not give chemo, and the decision should be made about what to do for that individual patient in that setting. Dr. Linda Duska: Agreed. And along those lines, if you look carefully at their data, the patients who had an upfront cytoreduction had almost twice the risk of having a stoma than the patients who had an interval cytoreduction. And they also had a higher risk of needing to have a bowel resection. The numbers were small, but still, when you look at the surgical complications, as you've already said, they're higher in the upfront group than they are in the interval group. That needs to be taken into account as well when counseling a patient, right? When you have a patient in front of you who says to you, "Dr. Moore, you can take out whatever you want, but whatever you do, don't make me a bag." As long as the patient understands what that means and what they're asking us to do, I think that we need to think about that. Dr. Kathleen Moore: I think that is a great point. And I have definitely seen in our practice, patients who say, "I absolutely would not want an ostomy. It's a nonstarter for me." And we do make different decisions. And you have to just say, "That's the decision we've made," and you kind of move on, and you can't look back and say, "Well, I wish I would have, could have, should have done something else." That is what the patient wants. Ultimately, that patient, her family, autonomous beings, they need to be fully counseled, and you need to counsel that patient as to the site that you are in, her volume of disease, and what you think you can achieve. In my opinion, a patient with stage III cancer who you have the site and the capabilities to get to no gross residual should go to the OR first. That is what I believe. I do not anymore think that for stage IV. I think that this is pretty convincing to me that that is probably a harmful thing. However, I want you to react to this. I think I am going to be a little unpopular in saying this, but for me, one of the biggest take-homes from TRUST was that whether or not, and we can talk about the subsets and the stage III looked better, and I think it did, but both groups did really well. Like, really well. And these were patients with large volume disease. This was not cherry-picked small volume stage IIIs that you could have done an optimal just by doing a hysterectomy. You know, these were patients that needed radical surgery. And both did well. And so what it speaks to me is that anytime you are going to operate on someone with ovary, whether it be frontline, whether it be a primary or interval, you need a high-volume surgeon. That is what I think this means to me. Like, I would want high volume surgeon at a center that could do these surgeries, getting that patient, my family member, me, to no gross residual. That is important. And you and I are both in training centers. I think we ought to take a really strong look at, are we preparing people to do the surgeries that are necessary to get someone to no gross residual 70% and 85% of the time? Dr. Linda Duska: We are going to run out of time, but I want to address that and ask you a provocative question. So, I completely agree with what you said, that surgery is important. But I also think one of the reasons these patients in this study did so well is because all of the incredible new therapies that we have for patients. Because OS is not just about surgery. It is about surgery, but it is also about all of the amazing new therapies we have that you and others have helped us to get through clinical research. And so, how much of that do you think, like, for example, if you look at the PFS and OS rates from CHORUS and EORTC, I get it that they're, that they're not the same. It's different patients, different populations, can't do cross-trial comparisons. But the OS, as you said, in this study was 54 months and 48 months, which is, compared to 2010, we're doing much, much better. It is not just the surgery, it is also all the amazing treatment options we have for these patients, including PARP, including MIRV, including lots of other new therapies. How do you fit that into thinking about all of this? Dr. Kathleen Moore: I do think we are seeing, and we know this just from epidemiologic data that the prevalence of ovarian cancer in many of the countries where the study was done is increasing, despite a decrease in incidence. And why is that? Because people are living longer. Dr. Linda Duska: People are living longer, yeah. Dr. Kathleen Moore: Which is phenomenal. That is what we want. And we do have, I think, better supportive care now. PARP inhibitors in the frontline, which not many of these patients had. Now some of them, this is mainly in Europe, will have gotten them in the first maintenance setting, and I do think that impacts outcome. We do not have that data yet, you know, to kind of see what, I would be really interested to see. We do not do this well because in ovarian cancer, post-progression survival can be so long, we do not do well of tracking what people get when they come off a clinical trial to see how that could impact – you know, how many of them got another surgery? How many of them got a PARP? I think this group probably missed the ADC wave for the most part, because this, mirvetuximab is just very recently available in Europe. Dr. Linda Duska: Unless they were on trial. Dr. Kathleen Moore: Unless they were on trial. But I mean, I think we will have to see. 600 patients, I would bet a lot of them missed the ADC wave. So, I do not know that we can say we know what drove these phenomenal – these are some of the best curves we've seen outside of BRCA. And then coming back to your point about the BRCA population here, that is a really critical question that I do not know that we're ever going to answer. There have been hypotheses around a tumor that is driven by BRCA, if you surgically cytoreduced it, and then chemically cytoreduced it with chemo, and so you're starting PARP with nothing visible and likely still homogeneous clones. Is that the group we cured? And then if you give chemo first before surgery, it allows more rapid development of heterogeneity and more clonal evolution that those are patients who are less likely to be cured, even if they do get cytoreduced to nothing at interval with use of PARP inhibitor in the front line. That is a question that many have brought up as something we would like to understand better. Like, if you are BRCA, should you always just go for it or not? I do not know that we're ever going to really get to that. We are trying to look at some of the other studies and just see if you got neoadjuvant and you had BRCA, was anyone cured? I think that is a question on SOLO1 I would like to know the answer to, and I don't yet, that may help us get to that. But that's sort of something we do think about. You should have a fair number of them in TRUST. It wasn't a stratification factor, as I remember. Dr. Linda Duska: No, it wasn't. They stratified by center, age, and ECOG status Dr. Kathleen Moore: So you would hope with randomization that you would have an equal number in each arm. And they may be able to pull that out and do a very exploratory look. But I would be interested to see just completely hypothesis-generating what this looks like for the patients with BRCA, and I hope that they will present that. I know they're busy at work. They have translational work. They have a lot pending with TRUST. It's an incredibly rich resource that I think is going to teach us a lot, and I am excited to see what they do next. Dr. Linda Duska: So, outside of TRUST, we are out of time. I just want to give you a moment if there were any other messages that you want to share with our listeners before we wrap up. Dr. Kathleen Moore: It's an exciting time to be in GYN oncology. For so long, it was just chemo, and then the PARP inhibitors nudged us along quite a bit. We did move more patients, I believe, to the cure fraction. When we ultimately see OS, I think we'll be able to say that definitively, and that is exciting. But, you know, that is the minority of our patients. And while HRD positive benefits tremendously from PARP, I am not as sure we've moved as many to the cure fraction. Time will tell. But 50% of our patients have these tumors that are less HRD. They have a worse prognosis. I think we can say that and recur more quickly. And so the advent of these antibody-drug conjugates, and we could name 20 of them in development in GYN right now, targeting tumor-associated antigens because we're not really driven by mutations other than BRCA. We do not have a lot of things to come after. We're not lung cancer. We are not breast cancer. But we do have a lot of proteins on the surface of our cancers, and we are finally able to leverage that with some very active regimens. And we're in the early phases, I would say, of really understanding how best to use those, how best to position them, and which one to select for whom in a setting where there is going to be obvious overlap of the targets. So we're going to be really working this problem. It is a good problem. A lot of drugs that work pretty well. How do you individualize for a patient, the patient in front of you with three different markers? How do you optimize it? Where do you put them to really prolong survival? And then we finally have cell surface. We saw at ASCO, CDK2 come into play here for the first time, we've got a cell cycle inhibitor. We've been working on WEE1 and ATR for a long time. CDK2s may hit. Response rates were respectable in a resistant population that was cyclin E overexpressing. We've been working on that biomarker for a long time with a toxicity profile that was surprisingly clean, which I like to see for our patients. So that is a different platform. I think we have got bispecifics on the rise. So there is a pipeline of things behind the ADCs, which is important because we need more than one thing, that makes me feel like in the future, I am probably not going to be using doxil ever for platinum-resistant disease. So, I am going to be excited to retire some of those things. We will say, "Remember when we used to use doxil for platinum-resistant disease?" Dr. Linda Duska: I will be retired by then, but thanks for that thought. Dr. Kathleen Moore: I will remind you. Dr. Linda Duska: You are right. It is such an incredibly exciting time to be taking care of ovarian cancer patients with all the opportunities.  And I want to thank you for sharing your valuable insights with us on this podcast today and for your great work to advance care for patients with GYN cancers. Dr. Kathleen Moore: Likewise. Thanks for having me. Dr. Linda Duska: And thank you to our listeners for your time today. You will find links to the TRUST study and other studies discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. More on today's speakers:   Dr. Linda Duska  @Lduska Dr. Kathleen Moore Follow ASCO on social media:     @ASCO on X (formerly Twitter) ASCO on Bluesky   ASCO on Facebook     ASCO on LinkedIn     Disclosures of Potential Conflicts of Interest:    Dr. Linda Duska:   Consulting or Advisory Role: Regeneron, Inovio Pharmaceuticals, Merck, Ellipses Pharma  Research Funding (Inst.): GlaxoSmithKline, Millenium, Bristol-Myers Squibb, Aeterna Zentaris, Novartis, Abbvie, Tesaro, Cerulean Pharma, Aduro Biotech, Advaxis, Ludwig Institute for Cancer Research, Leap Therapeutics  Patents, Royalties, Other Intellectual Property: UptToDate, Editor, British Journal of Ob/Gyn  Dr. Kathleen Moore: Leadership: GOG Partners, NRG Ovarian Committee Chair Honoraria: Astellas Medivation, Clearity Foundation, IDEOlogy Health, Medscape, Great Debates and Updates, OncLive/MJH Life Sciences, MD Outlook, Curio Science, Plexus, University of Florida, University of Arkansas for Medical Sciences, Congress Chanel, BIOPHARM, CEA/CCO, Physician Education Resource (PER), Research to Practice, Med Learning Group, Peerview, Peerview, PeerVoice, CME Outfitters, Virtual Incision Consulting/Advisory Role: Genentech/Roche, Immunogen, AstraZeneca, Merck, Eisai, Verastem/Pharmacyclics, AADi, Caris Life Sciences, Iovance Biotherapeutics, Janssen Oncology, Regeneron, zentalis, Daiichi Sankyo Europe GmbH, BioNTech SE, Immunocore, Seagen, Takeda Science Foundation, Zymeworks, Profound Bio, ADC Therapeutics, Third Arc, Loxo/Lilly, Bristol Myers Squibb Foundation, Tango Therapeutics, Abbvie, T Knife, F Hoffman La Roche, Tubulis GmbH, Clovis Oncology, Kivu, Genmab/Seagen, Kivu, Genmab/Seagen, Whitehawk, OnCusp Therapeutics, Natera, BeiGene, Karyopharm Therapeutics, Day One Biopharmaceuticals, Debiopharm Group, Foundation Medicine, Novocure Research Funding (Inst.): Mersana, GSK/Tesaro, Duality Biologics, Mersana, GSK/Tesaro, Duality Biologics, Merck, Regeneron, Verasatem, AstraZeneca, Immunogen, Daiichi Sankyo/Lilly, Immunocore, Torl Biotherapeutics, Allarity Therapeutics, IDEAYA Biosciences, Zymeworks, Schrodinger Other Relationship (Inst.): GOG Partners

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Financial Sense(R) Newshour

Play Episode Listen Later Nov 19, 2025 2:33


Nov 18, 2025 – Cracks are showing in the AI trade, warns Peter Boockvar. As US tech giants spend up to 50% of revenue on AI, Wall Street grows wary. With China releasing open-source models, Boockvar favors commodities and gold over big tech amid rising uncertainty.

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Play Episode Listen Later Nov 18, 2025 26:33


Nov 14, 2025 – Chris Hennessey shares tips on maximizing deductions, managing SALT limits, and estate planning essentials before 2026 tax law changes. Don't miss his expert advice for investors and high earners...

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Play Episode Listen Later Nov 15, 2025 44:36


Nov 14, 2025 – Are the days of tech dominance numbered? In this wide-ranging discussion, Jim Puplava and Greg Weldon warn that the so-called Mag 7 tech stocks are faltering, jeopardizing narrow market leadership and exposing investors to...

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Play Episode Listen Later Nov 14, 2025 27:29


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Financial Sense(R) Newshour

Play Episode Listen Later Nov 14, 2025 23:55


Nov 14, 2025 – Amid mounting concerns about market liquidity, Financial Sense's Chris Puplava explains why the Federal Reserve may soon intervene to stabilize short-term funding. As the Fed shrinks its balance sheet, reserves risk falling from “ample” to...

Financial Sense(R) Newshour
China Just Launched the Robotic Revolution; Humanoids Will Be Bigger Than ChatGPT, Says Nick Pardini (Preview)

Financial Sense(R) Newshour

Play Episode Listen Later Nov 13, 2025 3:10


November 13, 2025 – Robots are leaving the realm of science fiction and entering our homes, transforming everyday life. Today, on FS Insider, Cris Sheridan interviews Nick Pardini at Davos Investment Group about the rapid advancements in autonomous robotics and their societal impact. They discuss how breakthroughs in robotics, combined with AI, are making household tasks like cleaning, cooking,...

Financial Sense(R) Newshour
What's Next for Home Prices? Dr. Selma Hepp on Market Trends and 50-Year Mortgages (Preview)

Financial Sense(R) Newshour

Play Episode Listen Later Nov 11, 2025 2:38


Nov 11, 2025 – Curious about the future of U.S. housing? Dr. Selma Hepp, Chief Economist at Cotality, dissects the latest data and forecasts for the U.S. housing market. Dr. Hepp notes a continued slowdown in home price appreciation...

Financial Sense(R) Newshour
Red, Blue, and You: How Light Influences Sleep and Metabolism

Financial Sense(R) Newshour

Play Episode Listen Later Nov 11, 2025 31:52


Nov 10, 2025 – Struggling with sleep? Discover how the lighting in your home might be subtly impacting your health in this enlightening discussion between Dr. Mike Haga and Jim Puplava, as they delve into the latest research on light spectrum and intensity...

Financial Sense(R) Newshour
Marc Chandler on Dollar Correction, Gold Revaluation, and Currency Outlook

Financial Sense(R) Newshour

Play Episode Listen Later Nov 8, 2025 19:05


Nov 7, 2025 – Financial Sense welcomes Marc Chandler, chief strategist at Bannockburn Capital Markets, to discuss the outlook for the US dollar, why a gold revaluation to market prices makes sense, and his broader outlook for...

Financial Sense(R) Newshour
Jim Welsh on AI Correction, Government Shutdown, and Downside Risks

Financial Sense(R) Newshour

Play Episode Listen Later Nov 7, 2025 28:20


Nov 7, 2025 – AI and market concentration are reshaping Wall Street—and investors should beware. Financial Sense Newshour's Jim Puplava and Jim Welsh at Macro Tides dissect the recent pullback in major indexes, the outsized influence of...

Financial Sense(R) Newshour
Is America Headed for a Debt Crisis? Jim Puplava on the Road to $50 Trillion

Financial Sense(R) Newshour

Play Episode Listen Later Nov 7, 2025 32:23


Nov 7, 2025 – What if the United States is barreling toward a debt crisis that no one in Washington wants to acknowledge? In this urgent discussion, Cris Sheridan and Jim Puplava break down the alarming math behind America's fiscal future...

Financial Sense(R) Newshour
Why This Gold Pullback Changes Nothing: Alan Hibbard's $10K Price Target (Preview)

Financial Sense(R) Newshour

Play Episode Listen Later Nov 6, 2025 1:54


Nov 5, 2025 – What if the biggest financial shift of our generation isn't about stocks or bonds, but about returning to real money? In this compelling conversation, Cris Sheridan interviews precious metals specialist Alan Hibbard about the future of gold, silver, and Bitcoin...