Podcasts about PFS

Mar 20, 2026 – Gold and silver are dropping when they should be rallying, inflation is far from tamed, and looming global debt could upend the markets at any moment—are we on the cusp of a financial reckoning that no one sees coming?

Mar 19, 2026 – The situation in the Middle East continues to escalate as the damage broadens from military targets to energy infrastructure, which has longer-lasting impacts on the price of oil, gas, fertilizer, and more. Chris Puplava says that markets...

Mar 20, 2026 – What if the fiercest threat to America's future isn't armies or missiles—but a silent, strategic assault on the global commodities markets? In this riveting conversation, host Jim Puplava speaks with systems thinker Craig Tindale, who warns...

Mar 18, 2026 – Is the recent volatility in energy markets a precursor to a cyclical downturn, or has the U.S. consumer achieved a new level of structural decoupling from energy price shocks? Join Cris Sheridan and ITR Economics' Lauren Saidel-Baker...

Mar 16, 2026 – What if breathing pressurized oxygen could be the key to unlocking your body's ability to heal and reverse cellular aging? In this fascinating conversation, Jim Puplava sits down with Shah Haq, director of engineering at...

Mar 14, 2026 – Financial Sense Newshour's Jim Puplava and Cris Sheridan explore how global supply chains, critical minerals, and strategic vulnerabilities are reshaping geopolitics amidst the ongoing Middle East conflict. They examine the material...

Mar 13, 2026 – Mish Schneider at Market Gauge tells Financial Sense Newshour why she's raised cash while holding to a core position of commodities given the current trends in the market. Mish says that one of the most important sectors she follows...

Mar 12, 2026 – Is the world prepared for the reality of $150-200 oil? In this sobering conversation, Jim Puplava and energy analyst Robert Rapier discuss the escalating Iran War and the "nuclear option" currently paralyzing global trade...

David Stewart discusses Minera Alamos' recent resource update at the Pan Gold Mine which showed Proven and Probable Reserves of 222 thousand ounces. David also discusses the Gold Rock project integration plans into the Pan Complex and a highly anticipated PFS for the Copperstone asset. The company is also planning a strategic rebranding to focus on US growth.

Mar 10, 2026 – After oil spiked near $120 this week, prices tumbled following President Trump's bold claim that the conflict is nearing its end. Yet, with conflicting reports and fresh news of potential Iranian mining operations, the Strait of Hormuz...

Mar 10, 2026 – While President Trump declares the mission accomplished, geopolitical strategist Christian Takushi warns the real conflict is only beginning. In this explosive episode, we peel back the curtain on the "Strategic Sabotage" of 2026...

Mar 9, 2026 – What if the secret to reversing the aging process wasn't found in a pill, but in the fundamental elements of nature? Jason Tebeau reveals the Superhuman Protocol, a groundbreaking three-step system designed to "recharge"...

Mar 6, 2026 – How much of an impact with the Iran war and spiking oil prices have on inflation, widely expected Fed rate cuts, and the markets? Jim Puplava sits down with renowned market strategist Jim Bianco for a wide-ranging discussion...

Mar 6, 2026 – When energy markets and geopolitical tensions collide, does the traditional investment playbook still hold? With oil surpassing $90 a barrel, investors are facing a complex landscape of supply chain vulnerabilities and inflationary pressures.

In this episode of the Oncology Brothers podcast, we dived deep into the complexities of multiple myeloma treatment, focusing on the groundbreaking MajesTEC-3 trial. We had the pleasure of welcoming Dr. Luciano Costa from the University of Alabama, who shared insights on the combination of teclistamab and daratumumab for relapsed refractory multiple myeloma. Listen us on: Spotify: https://open.spotify.com/show/31BXhY9FM4gPWG10WgE11o Follow us on social media: X/Twitter: https://twitter.com/oncbrothers Instagram: https://www.instagram.com/oncbrothers Website: https://oncbrothers.com/ Key topics discussed included: The impressive progression-free survival (PFS) rates observed in the MajesTEC-3 trial, with a PFS of 83.4% at three years. The mechanism of action of teclistamab as a bispecific antibody targeting BCMA and its synergy with daratumumab. Safety profiles, including the management of cytokine release syndrome (CRS) and infection risks, along with the use of IVIG for prophylaxis. The evolving landscape of multiple myeloma therapies, including the role of CAR T-cell therapy versus bispecific antibodies. Join us for this informative discussion that aims to keep healthcare professionals updated on the latest advancements in multiple myeloma treatment. Don't forget to like, subscribe, and check out our other episodes for more insights on oncology! #MultipleMyeloma, #MajesTEC3, #Teclistamab, #Daratumumab, #BispecificAntibody, #OncBrothers

Mar 5, 2026 – Geopolitics has overtaken economics as the primary driver of global markets. In this high-stakes conversation, Jim Puplava sits down with Ron William from RW Advisors to break down the convergence of multiple major cycles...

Interview with Hugh Agro, CEO, Revival GoldOur previous interview: https://www.cruxinvestor.com/posts/revival-gold-tsxvrgv-undervalued-investment-series-with-hugh-agro-9318Recording date: 3rd of March 2026Revival Gold has announced significant drill results from the South Mercur area of its Utah-based Mercur project, intersecting over 4 grams per ton gold across 25 meters with favorable leachability characteristics. The results mark the first holes from this newly consolidated portion of the 7,200-hectare property, which includes ground previously operated separately by Homestake and never coordinated with adjacent historic Mercur operations.The discovery comes as Revival Gold executes a detailed development timeline targeting 2029 production of approximately 100,000 ounces annually from its heap leach operation. The company has outlined a comprehensive 2026 work program including 16,000 meters of drilling, baseline studies across biological, cultural, and hydrological domains, and engineering work advancing toward pre-feasibility study (PFS) completion in early 2027.Mercur's current economic assessment demonstrates compelling returns, with $750 million in after-tax net present value at $3,000 gold, rising to $1.2 billion at $4,000 gold. At a 57% internal rate of return, the project would generate approximately $350 million in annual free cash flow at current gold prices above $5,000 per ounce, establishing it as Utah's largest gold producer.The project benefits from rare brownfield advantages including location entirely on private land, existing power and water infrastructure, and extensive historical data from previous operations. These factors reduce both capital intensity and permitting risks compared to typical greenfield developments or projects on public lands.Despite these attributes, Revival Gold trades at approximately 0.15x net asset value, with analyst price targets two to three times current levels. CEO Hugh Agro attributes the discount to development-stage risk perception, expecting multiple re-rating as the company demonstrates execution through 2026-2027 milestones.Beyond Mercur, the company's 4.6 million ounce Beartrack-Arnett project in Idaho provides additional portfolio value, with two drill rigs currently testing high-grade underground potential. The dual-asset strategy offers exploration upside while maintaining focus on Mercur's path to production, backed by institutional support from EMR Capital, Konwave, and Dundee.Learn more: https://www.cruxinvestor.com/companies/revival-gold-incSign up for Crux Investor: https://cruxinvestor.com

Mar 4, 2026 – Discover how Iran's turmoil fits into a high-stakes global chess match between the US and China. In this episode, FS Insider's Cris Sheridan and Edward Gustely unravel the real motives behind America's strategy in the Middle East...

Interview with Heye Daun, President & CEO of Koryx Copper Inc.Our previous interview: https://www.cruxinvestor.com/posts/koryx-copper-tsxvkry-seasoned-executives-aim-to-unlock-value-in-huge-namibian-copper-project-6281Recording date: 1st March 2026Koryx Copper Inc. is developing the Haib copper project in Namibia, one of sub-Saharan Africa's most stable and established mining jurisdictions. Under the leadership of CEO Heye Daun, a Namibian citizen, mining engineer, and serial dealmaker, the company has transformed a previously mismanaged junior mining asset into a credible large-scale copper development opportunity in under two years.The Haib project was drilled originally by Rio Tinto in the 1970s but was left undeveloped as copper prices at the time did not support a low-grade sulfide deposit. It eventually passed to Deep South Resources, which proposed bio-heap-leach processing, a method not proven at commercial scale for sulfide material, and subsequently lost its operating licenses. When Daun's team assumed control, they reinstated conventional milling and flotation, the standard and bankable processing route for sulfide copper, and rebuilt both the technical and financial credibility of the asset from the ground up.The resulting PEA published in 2025 modelled just under 100,000 tonnes of annual copper production at a capital cost of approximately $1.5 billion, using a copper price of $4.30 per pound which roughly 30% below spot at the time of the PDAC 2026 interview. The middle-of-the-cost-curve economics hold up at conservative assumptions, and management's stated approach to study assumptions has historically been validated: on both prior Namibian transactions, the step from PEA to PFS maintained or improved the project scope rather than contracting it.The next milestone is the PFS, expected by end of 2026. This study will sharpen engineering and cost estimates, providing a more bankable document for potential financing discussions and strategic partner conversations. Alongside the PFS, Koryx is expanding its mineral resource and adding exploration ground around the Haib project, with a new, larger resource estimate expected in the near term.Financially, the company has moved from a $10 million market capitalisation to raising over $100 million, including a $51 million institutional placement that attracted Middle Eastern and Chinese financial groups as strategic participants. The company states it is sufficiently capitalised to reach an investment decision without further dilutive financing in the near term.The long-term construction path is expected to involve a major mining company or capital partner given the scale of investment required. Daun has been explicit about this: a $1.5 to $2 billion project is beyond the appropriate scope for a junior developer to build independently. Whether that takes the form of a joint venture, acquisition, or offtake-led financing arrangement will be determined in part by prevailing market conditions and the company's share price at the time of the investment decision.For investors, the near-term investment case rests on two catalysts: the mineral resource expansion and the PFS delivery. Both are well-defined, time-bounded events that, if executed credibly, represent meaningful de-risking steps for an asset that already has institutional and strategic interest at the door.View Koryx Copper's company profile: https://www.cruxinvestor.com/companies/koryx-copperSign up for Crux Investor: https://cruxinvestor.com

Mar 2, 2026 – In this urgent and in-depth conversation, FS Insider interviews geopolitical analyst Jacob Shapiro after the ongoing US-Israel military operation against Iran. Shapiro unpacks the real-time complexities—from the risks of regime...

Febr 27, 2026 – Is the strong bull market starting to lose momentum? Financial Sense Newshour's Jim Puplava interviews market strategist Jim Welsh of Macro Tides for a technical deep dive into what's really going on under the market's surface...

Feb 27, 2026 – Can America win the AI race if it can't keep the lights on? In this electrifying conversation, Jim Puplava sits down with energy experts Robert Bryce and Doomberg to unpack the explosive collision between artificial intelligence...

Feb 26, 2026 – Is the world drifting toward a new era of global conflict — one that doesn't look like the wars of the past? In this gripping interview, Martin Armstrong lays out why today's geopolitical tensions may be part of a much larger historical cycle...

Feb 25, 2026 – Last week's Supreme Court ruling upended President Trump's sweeping tariff strategy, cutting the effective U.S. tariff rate nearly in half and sending shockwaves through global trade. Adriano Bosoni breaks down who wins and who loses...

Dr. Lakshmi Rajdev and Dr. Manish Shah join the podcast to discuss the updated guideline on immunotherapy and targeted therapy in unresectable locally advanced, advanced, or metastatic gastroesophageal cancer. They share first-line and subsequent-line recommendations for both gastroesophageal adenocarcinoma and esophageal squamous cell carcinoma based on actionable biomarkers including PD-L1 expression, MMR and/or MSI, CLDN18.2 expression, and HER2 status. They note the importance of the algorithms and tables in the guidelines that provide visual illustrations and quick reference guides of the evidence-based recommendations. They also comment on ongoing and recently presented trials that may impact future guidelines in this space. Read the full guideline, "Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer: ASCO Guideline Update" at www.asco.org/gastrointestinal-cancer-guidelines" TRANSCRIPT This guideline, clinical tools and resources are available at www.asco.org/gastrointestinal-cancer-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology,  https://ascopubs.org/doi/10.1200/JCO-25-02958      Timestamps ·       00:00 – 02:15 Introduction and Overview ·       02:16 - 08:20 First-line treatment for patients with pMMR/MSS, HER2-negative gastroesophageal adenocarcinoma ·       08:21 –10:29 First-line treatment for patients with pMMR/MSS, HER2-positive gastroesophageal adenocarcinoma ·       10:30 – 14:39 First-line treatment for patients with dMMR/MSI-H, gastroesophageal adenocarcinoma ·       14:40 – 18:03 First-line treatment for ESCC ·       18:04 – 22:04 Second- and third-line therapy for gastroesophageal adenocarcinoma and ESCC ·       22:05 – 24:38 Importance of guideline ·       24:39 – 27:45 Outstanding questions and future research   Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts.   My name is Brittany Harvey, and today I am interviewing Dr. Lakshmi Rajdev from the Icahn School of Medicine at Mount Sinai and Dr. Manish Shah from Weill Cornell Medicine, co-chairs on "Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer: ASCO Guideline Update." Thank you for being here today, Dr. Rajdev and Dr. Shah. Dr. Lakshmi Rajdev: Thank you. Dr. Manish Shah: Thank you for having us. It is wonderful. Brittany Harvey: And then just before we discuss this guideline, I would like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Rajdev and Dr. Shah, who have joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes. So then to dive into what we are here today to talk about, Dr. Shah, I would like to start first with what prompted the update to this guideline, which was previously published in 2023, and what is the scope of this updated guideline? Dr. Manish Shah: Yes, terrific. So even in the last few years, the pace of drug development in gastroesophageal cancers has just been astounding. So, what prompted this guideline is actually the practice-changing results for a new biomarker, CLDN18.2 hat was based on the GLOW and SPOTLIGHT studies, as well as a practice-changing study in HER2-positive disease where we added pembrolizumab to trastuzumab and chemotherapy for tumors that are HER2-positive and PD-L1 CPS 1 or greater. And then there were also new studies and new approvals in esophageal squamous cell cancer that you will hear about as well. So there were several studies, overall more than 5,000 patients were reported on, and that led to several new therapies, new indications, and it really necessitated this guideline. Brittany Harvey: Excellent. It is great to hear about all of these exciting updates in this space. So then to next review the key recommendations of this guideline by clinical question that the expert panel addressed. So, Dr. Rajdev, what is the recommended first-line treatment for patients with proficient mismatch repair, microsatellite stable, HER2-negative gastroesophageal adenocarcinoma? Dr. Lakshmi Rajdev: Thank you for that question. So historically, we have sort of used fluoropyrimidine and platinum doublets, which yielded a survival of about one year. More recently, immunotherapy and targeted therapy options have improved outcomes in patients with advanced esophageal and gastric adenocarcinoma, as well as squamous cell carcinoma. Patients with gastric and GE junction adenocarcinoma have a high rate of actionable alterations, so it is imperative that physicians test the following biomarkers upfront so that it can help guide therapy. The markers recommended by the ASCO panel are HER2, MMR or MSI, CLDN18.2, and PD-L1. And also, it was recommended to use NGS if feasible in this patient population. HER2, as we know, is expressed in about 15% to 25% of patients; PD-L1 expression occurs in about 80% of patients; MSI-high, deficient MMR is present in about 5% to 8% of patients; and CLDN18.2 expression is present in about 40% of patients. There is, of course, biomarker overlap. About 13% to 22% of CLDN18.2 patients are also PD-L1 positive. For patients with pMMR or microsatellite stable HER2-negative disease with PD-L1 expression greater than 1 and absence of CLDN18.2, the panel recommended a first-line therapy with fluoropyrimidine and platinum-based therapy in combination with immunotherapy. These recommendations stem from large phase 3 trials, and the agents approved in the United States are pembrolizumab, nivolumab, and tislelizumab. It has been shown that immunotherapy benefit is greater in patients with higher PD-L1 expression, and it is not possible to comment on the individual PD-L1 cutoff scores and sort of identify the optimal PD-L1 cutoff score that sort of balances benefits and harms. But what is recommended is that immunotherapy-based treatments can be offered in patients with a CPS score of greater than 1. With regard to the choice of immunotherapy agents, that is pembrolizumab, nivolumab, or tislelizumab, these agents are considered to have similar efficacy, and the selection of an agent could be based on dosing schedule, cost considerations, toxicity, and the method of administration. Typically, clinicians should avoid withholding the start of chemotherapy while awaiting biomarker testing, depending on the clinical scenario. Now, for patients with pMMR microsatellite stable disease that is HER2-negative with PD-L1 expression less than 1 and positive CLDN18.2 expression, zolbetuximab-based treatments or in combination with chemotherapy is recommended, and this is based on two global phase III randomized controlled trials, the GLOW and the SPOTLIGHT. And across both studies, the hazard ratio for the overall survival was 0.78, and similarly, there was also an improvement in progression-free survival favoring the zolbetuximab group compared to the chemotherapy group alone. An important note is that nausea, vomiting is commonly associated with zolbetuximab-based treatments, and the panel recommended prophylactic antiemetics, adjusting zolbetuximab infusion rates, pausing infusion temporarily, using non-prophylactic antiemetics, and hydration intravenously prior to discontinuation of zolbetuximab-based chemotherapy. So effective handling of the GI-related symptoms with zolbetuximab is recommended prior to discontinuation of therapy. Now, for patients with pMMR microsatellite stable HER2-negative gastric, GE junction adenocarcinoma with PD-L1 expression greater than 1 and CLDN18.2 positivity, the ones with the dual expression with CLDN18.2 as well as PD-L1 chemotherapy, the choice of therapy can be based on the degree of PD-L1 expression, the toxicity profile, the burden of symptoms, and the anticipated improvement in symptoms associated with response to treatment, the patient comorbidities, the prior medical and treatment history. So this decision needs to be made on a case-by-case basis, and these are some of the factors that we suggested that could potentially influence the choice of therapy. For patients with pMMR microsatellite stable disease that is HER2-negative and a PD-L1 expression less than 1 and an absence of CLDN18.2 expression, first-line therapy with fluoropyrimidine and platinum-based chemotherapy is recommended. So you can see we have segmented out patients based on PD-L1 expression, pMMR and microsatellite stable disease expression, and also based on CLDN expression. Brittany Harvey: Absolutely. And that first point you noted, I think is really important, that biomarker testing is really critical for treatment decision-making in this space. So then the next subgroup of patients that the panel looked at, Dr. Shah, what first-line therapy is recommended for patients with proficient mismatch repair, microsatellite stable, HER2-positive gastroesophageal adenocarcinoma? Dr. Manish Shah: So this was an update from a few years ago. So we have known for 15 years now that if you are HER2-positive, you should get trastuzumab plus chemotherapy. That was based on the ToGA trial. And the update now is based on a trial called KEYNOTE-811, where it examined the addition of pembrolizumab to trastuzumab and chemotherapy versus trastuzumab and chemotherapy, and there was a progression-free and overall survival benefit. And again, here, the biomarkers are important. If your CPS PD-L1 is less than 1, we would not recommend Pembrolizumab in that setting, so you would still get trastuzumab and chemotherapy. But if it is 1 or greater, the PD-L1 CPS score, then we do recommend pembrolizumab unless there is a contraindication to immunotherapy. The take-home message really is from the onset of diagnosis, please check your biomarkers. And I will just, it is worth repeating, it is important to check your PD-L1 status, HER2 status, mismatch repair status, and CLDN18.2 status. And then the optimal therapy, and it is outlined in the publication, is really biomarker-driven. We know that if we are able to hit the target that is overexpressed, we are going to have a better outcome. And Dr. Rajdev did mention where there is overlap, there can be a lack of data, and that is where we are with both PD-L1 positive and CLDN positive. Here we do have data in HER2-positive cases where if you are both HER2-positive and PD-L1 positive, you would combine trastuzumab and pembrolizumab for the best outcomes. Brittany Harvey: Understood. I really appreciate you detailing what is most important for each individual biomarker combination that patients may have. So then following that, Dr. Rajdev, what does the expert panel recommend for first-line treatment for patients with esophageal squamous cell carcinoma that is not amenable to definitive chemoradiation? Dr. Lakshmi Rajdev: There are three phase III randomized clinical trials that have influenced practice in patients with esophageal squamous cell carcinoma examining the benefit of immunotherapy in this patient population. The RATIONALE-306 was a randomized trial of tislelizumab plus chemotherapy with platinum and fluoropyrimidine or paclitaxel versus placebo with chemotherapy. And then you have the KEYNOTE-590, which compared pembrolizumab plus chemotherapy versus chemotherapy alone. And then you have CheckMate-648, which included comparisons of nivolumab plus chemotherapy versus nivolumab plus ipilimumab or chemotherapy. And the primary endpoints for these studies were overall survival, and they did look at subgroups with PD-L1 expression. They used TPS score greater than 1% in CheckMate-648 and PD-L1 CPS greater than 10 in KEYNOTE-590. The bottom line is that the overall hazard ratio for overall survival across this patient population was 0.72. So clearly, there is benefit in patients that express PD-L1 CPS greater than 1 for benefit for the addition of immunotherapy. Now, the benefit again in patients with a PD-L1 expression less than 1 remains limited, and so the panel has made a recommendation for using immunotherapy in combination with platinum-based chemotherapy in patients with a PD-L1 greater than 1. Again, we know that it is hard to make recommendations on what PD-L1 cutoffs are recommended in this patient population, meaning that should it be limited to patients with a PD-L1 of 1 to 4 or greater than 10? I think that the general consensus that has been gleaned from the data is that the higher the PD-L1 expression, the greater the benefit. I do want to comment on another option that is available in patients with squamous cell carcinoma compared to adenocarcinoma, and that is the combination of nivolumab and ipilimumab. Now, in CheckMate-648, nivolumab with ipilimumab was also recommended as a treatment option in patients that have a PD-L1 score of greater than 1. There was a survival benefit demonstrated with this combination compared to chemotherapy alone. And an important observation in this study is that, although there was a slightly increased rate in early death, but there was really no significant difference in PFS and OS compared to chemotherapy alone. Importantly, the treatment appeared to be pretty well tolerated by the study population. There was a notable difference in the objective response rate, which was 35% in the nivolumab plus ipilimumab group compared to patients receiving nivolumab and chemotherapy, where it was 53%. So superiority is, so the importance of chemotherapy in patients with esophageal squamous cell carcinoma is to be noted. However, there is no difference in overall survival and progression-free survival when using the combination of nivolumab and ipilimumab, and thus it affords a chemotherapy-free option for this patient population with esophageal squamous cell carcinoma and a CPS with a score of greater than 1. Brittany Harvey: Understood. I appreciate you reviewing the evidence underpinning those recommendations as well. So then the next patient population that the guideline panel addressed, what first-line therapy is recommended for patients with deficient mismatch repair, microsatellite instability-high, gastroesophageal adenocarcinoma or esophageal squamous cell carcinoma? Dr. Lakshmi Rajdev: The rate of MSI-high expression is about 3% to 7% across different studies. Now, the KEYNOTE-158 was a tumor-agnostic study in patients with non-colorectal cancers, and again, the problem with the MSI-high population, given that it is so rare, the numbers in the individual studies are fairly small. But consistent outcomes do emerge, indicating high response to immunotherapy. So in KEYNOTE-158, a response rate of about 46% was noted. The number of patients was small, it was about 24. In CheckMate-649, which is a study of chemotherapy plus or minus nivolumab in patients with advanced gastric adenocarcinoma, there was again a very small number of patients, and patients that were MSI-high or deficient MMR did experience substantial benefits with the addition of immunotherapy, with hazard ratios in the order of about 0.38. In KEYNOTE-062, again, it was a very small number of patients, again about 6% or so, and similar to CheckMate-649, a substantial benefit was noted in combination with chemotherapy, but also there were benefits noted with pembrolizumab alone. The RATIONALE-305 again was a study of tislelizumab in combination with chemotherapy and similarly showed benefits to the combination of chemotherapy plus immunotherapy in this patient population. I think that we are all aware of the dramatic benefits of immunotherapy in this particular subset of patients, deficient MMR MSI-high, and also we have seen in CheckMate-649 they did have a subset of patients that received nivolumab and ipilimumab. And in this patient population, they noted unstratified hazard ratio of 0.28. So I think that the overall consensus is that immunotherapy is a very important treatment modality in patients with deficient MMR MSI-high disease, given that a lot of the trials in gastroesophageal adenocarcinoma have utilized chemotherapy-based options, that is certainly a recommendation of the panel to use chemotherapy in combination with immunotherapy. However, on a case-by-case basis, the panel recommended immunotherapy alone as well, and given the high response rates noted in trials across different diseases as well as noted in this disease as well. Brittany Harvey: Certainly. And I appreciate you both for reviewing these first-line recommendations. So moving to later lines of therapy, Dr. Rajdev, what recommendations did the expert panel make for second or third-line therapy for gastroesophageal adenocarcinoma and esophageal squamous cell carcinoma? Dr. Lakshmi Rajdev: So, I think that the RAINBOW trial that investigated the utility of the addition of ramucirumab as second-line therapy has been around since 2014, and those results have led to the addition of ramucirumab to taxane-based therapy in the second-line setting. Based on the utilization of oxaliplatin and platinum-based therapy in the front-line setting, there may be patients that have an underlying neuropathy, and so we wanted to really include treatment options for this patient population so that an agent that is less neurotoxic could also be recommended in combination with ramucirumab. The RAMIRIS trial is one such trial where ramucirumab was combined with FOLFIRI, and it demonstrated benefit in combination with ramucirumab. So we have listed that as a potential treatment option for patients in the second-line setting who may have an underlying neuropathy or even for whatever reason that based on the toxicity profile, that needs to be the preferred option by a physician, that recommendation is new from the older guidelines that we have. With regard to the utility of PD-1 inhibitors, there really has been no benefit noted in the second-line setting with regard to overall survival or progression-free survival, so no recommendation is made for that option. I think an important study that has been recently presented is the DESTINY-Gastric04 trial, which really has been practice-changing and has led to the recommendation for trastuzumab deruxtecan in patients that have HER2-positive metastatic gastric or GE junction adenocarcinoma. Now, this is a phase III trial in patients who retained HER2-positive disease after progressing on front-line trastuzumab-based treatments, and the comparator for this trial was trastuzumab deruxtecan versus ramucirumab plus paclitaxel. There was significant improvement and progression-free survival in patients that received trastuzumab deruxtecan. The patients that were excluded from the trial are patients that have pulmonary problems, interstitial lung disease; that is one of the toxicities of this particular agent, and close monitoring and prompt initiation of therapy such as glucocorticoid treatment in patients who develop this toxicity was also highlighted by the panel. So to summarize, the new guidelines highlight the possibility of FOLFIRI plus ramucirumab as a second-line option and then trastuzumab deruxtecan as a later-line option in patients that still retain HER2 expression. And that is very important because the trial did retest patients whether they expressed HER2. As we know, in a substantial number of patients, there is downregulation of HER2, and there is emerging data that the benefit for subsequent HER2-directed therapies is best noted in patients that still retain HER2 expression. Brittany Harvey: Great. So as our listeners have heard, there are many recommendations and new treatment options for advanced gastroesophageal cancer. Dr. Shah, earlier you highlighted the importance of biomarker testing, but I would like to hear in your view, what is the importance of this guideline and how will it impact both clinicians and patients with gastroesophageal carcinoma? Dr. Manish Shah: So as we have discussed throughout this podcast, the treatment for gastroesophageal cancer, both adenocarcinoma and squamous cell cancer, is increasingly complex, increasingly biomarker-driven. And I think the value of the guideline is to place all of that into context. So it provides the data for why certain biomarkers are important, what therapies should be indicated. Not only that, but if you are able to review the guideline, it provides the details of each of these studies and summarizes them in a meta-analysis fashion to sort of give you the context, because sometimes the individual studies can be maybe a little bit discordant or confusing and the guideline attempts to harmonize all that. And then also, I think the tables are very, very interesting because they give you actual numbers in terms of how many patients over a thousand would this benefit or how many patients over a thousand would this cause harm in terms of nausea, vomiting, or other things like that. So it gives you context for helping clinicians and patients weigh the potential benefits of the novel treatment strategies against the potential adverse events. And then finally, the guideline does also provide an algorithm that you are able to follow based on the biomarkers, and those are in figures 4 and 5. So I think overall, it is a very comprehensive guideline. It intends to make more manageable a very complex subject, and you know, I really encourage our listeners to review it after listening to the podcast. Dr. Lakshmi Rajdev: If I can add to that, I think that what is also really good about the guidelines is there are quick summaries. So if someone is busy in the clinic, of course, there is the opportunity to review the data supporting the guidelines in great depth in the manuscript, but what is also really good is that there are good summaries. In the event that you are very busy, you can easily identify what the recommendations should be for that particular patient based on these summaries. Brittany Harvey: Absolutely. Listeners are encouraged to review the full guideline, including those tables and figures that may be more helpful when they are looking for something quick to look at in the clinic as well. So, as you both mentioned, there have been a number of recent practice-changing trials in this area. So I imagine there is still a lot of ongoing research as well. So Dr. Shah, what are the outstanding questions regarding treatment options for patients with locally advanced unresectable, advanced, or metastatic gastroesophageal carcinoma? Dr. Manish Shah: I think we touched upon it a little bit. The guidelines are based on the data available, and they are primarily examining one novel therapy with chemotherapy in a specific biomarker population. But as you know, the biomarkers are not either/or; you are not either CLDN18.2 positive or PD-L1 positive. A portion of patients could have dual biomarkers, and you know, I think that we are generating data on how to manage those patients. At the recent GI Symposium in January this year, the ILUSTRO trial was presented by Dr. Shitara, which looked at combining zolbetuximab and chemotherapy with immunotherapy for dual-positive biomarkers, and that is leading to a phase III study that has begun to enroll. So unanswered questions are: how do we manage dual-positive biomarkers? The other thing that was mentioned is that the current data for mismatch repair deficiency involve chemotherapy plus immunotherapy. Only squamous cell cancer is there a study with a positive non-chemotherapy kind of backbone, that is CheckMate-648 that Dr. Rajdev mentioned. As we move forward, it will be good to get data on non-chemotherapy options in certain biomarker-positive populations. And then finally, another update, which is likely to be practice-changing, is the HERIZON-GEA-01 study that looked at zanidatamab, which is another biparatopic antibody that targets HER2, and that is likely to change practice. And as that data gets published, we may look to even do a rapid update for the current immunotherapy and targeted therapy guideline that is just being published. Dr. Lakshmi Rajdev: So, if I can add to that, there are numerous ADCs that look very interesting. There are bispecific antibodies; in fact, the zanidatamab is a bispecific antibody showing improved activity in patients with HER2-positive disease. So I think there are studies from Asia looking at CLDN CAR T-based therapies. So, I think that there are a lot of novel agents and a lot of excitement in the field. We know that the bemarituzumab study, unfortunately, the FGFR2 inhibitor failed to demonstrate any benefit, but I think that there are other agents that are being explored, so there are newer targets, newer agents, ADCs, bispecifics that could potentially change the field in the future. Brittany Harvey: Yes, we will look forward to the data to address these unanswered questions and new agents and inform future guideline updates. So, I would like to thank you both for all of your work to review the evidence here and update this important guideline, and for your time today, Dr. Rajdev and Dr. Shah. Dr. Lakshmi Rajdev: Thank you. Dr. Manish Shah: Thank you. Brittany Harvey: And finally, thank you to all of our listeners for tuning in to the ASCO Guidelines podcast. To read the full guideline, go to www.asco.org/gastrointestinal-cancer-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, which is available in the Apple App Store or the Google Play Store. If you have enjoyed what you have heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode. The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Feb 24, 2026 – What if the massive disruption we've seen in the stock market from AI is just the beginning of a much deeper transformation? In this compelling conversation, Cris Sheridan sits down with strategist Robert Van Battenburg...

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What is really happening with the PFS? In this episode, Cary Sinnett talks with Matt Kidd, Chair of the AICPA PFS Credential Committee, about the modernization of the PFS Credential, including updating the PFS experienced exam, building the PFP Champions program, expanding avenues to earn the PFS Credential like the PFS Live workshop, growing the visibility of the PFS credential nationwide by highlighting CPA/PFS Financial Planners. They discuss why tax is becoming the gravitational center of financial planning, how CPA financial planners are uniquely positioned to deliver integrated advice, and what both seasoned CPAs and the next generation should understand about the power of adding the PFS. Top Takeaways •    The PFS exam and Body of Knowledge are being updated to reflect real-world, tax-integrated planning. •    CPA financial planners have a structural advantage in delivering holistic advice. •    Raising awareness starts with proudly displaying the CPA/PFS credential. PFS Resources: •    PFS Credential •    PFS Live Workshop •    PFS Handbook  •    PFS Business Experience •    PFS Infographic •    Earning your credential info •    Engage 2026  This episode is brought to you by the AICPA's Personal Financial Planning Section, the premier provider of information, tools, advocacy, and guidance for professionals who specialize in providing tax, estate, retirement, risk management and investment planning advice. Also, by the CPA/PFS credential program, which allows CPAs to demonstrate competence and confidence in providing these services to their clients. Visit us online to join our community, gain access to valuable member-only benefits or learn about our PFP certificate program. Subscribe to the PFP Podcast channel at Libsyn to find all the latest episodes or search "AICPA Personal Financial Planning" on your favorite podcast app.      

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Guest Full Name: Dr. R. Stacy Lindborg, PhDGuest Title: President, Chief Executive Officer, and Board DirectorCompany: IMUNONTicker: IMNNWebsite: https://imunon.com/Guest Bio:Stacy R. Lindborg, PhD, was appointed President and Chief Executive Officer of IMUNON in May 2024. Dr. Lindborg has served on IMUNON's Board of Directors since June 2021. She has nearly 30 years of experience in the pharmaceutical and biotech industries, with a particular focus on R&D, regulatory affairs, executive management, and strategy development. She has designed, hired, and led global teams, guiding long-term visions for growth through analytics and stimulating innovative development platforms to increase productivity.Prior to joining IMUNON, Dr. Lindborg was Executive Vice President and Co-Chief Executive Officer at BrainStorm Cell Therapeutics, where she remains a member of the company's Board of Directors. At BrainStorm, she was accountable for creating and executing clinical development strategies through registration and launch and progressed its novel cell therapy for ALS through a positive Phase 3 Special Protocol Assessment (SPA) study with the U.S. Food and Drug Administration. She frequently interacted with investors and analysts, represented the company in the scientific community and with the media, and played an active role in discussions with potential business partners.Dr. Lindborg previously was Vice President and Head of Global Analytics and Data Sciences, responsible for R&D and marketed products at Biogen. She began her biopharmaceutical career at Eli Lilly and Company, where, over the course of 16 years, she assumed positions of increasing responsibility, including Head of R&D strategy.Dr. Lindborg received an MA and PhD in statistics, and a BA in psychology and math from Baylor University. She has authored more than 200 presentations and 90 manuscripts that have been published in peer-reviewed journals, including 20 first-authored. She has held numerous positions within the International Biometric Society and American Statistical Association and was elected Fellow in 2008.Company Bio:IMUNON is a clinical-stage biotechnology company focused on advancing a portfolio of innovative treatments that harness the body's natural mechanisms to generate safe, effective, and durable responses across a broad array of diseases. IMUNON is developing its non-viral DNA technology across its modalities. The first modality, TheraPlas®, is developed for the gene-based delivery of cytokines and other therapeutic proteins in the treatment of solid tumors where an immunological approach is deemed promising. The second modality, PlaCCine®, is developed for the gene delivery of viral antigens that can elicit a strong immunological response.IMUNON's lead clinical program, IMNN-001, is a DNA-based immunotherapy for the localized treatment of advanced ovarian cancer. IMNN-001 is the first therapy to achieve a clinically effective response in advanced (stage IIIC/IV) ovarian cancer including benefits in both progression-free survival (PFS) and overall survival (OS) in a first-line treatment setting when used with standard of care chemotherapy. IMUNON has completed multiple clinical trials evaluating the potential of IMNN-001, including one Phase 2 clinical trial (OVATION 2), and is currently conducting a Phase 3 clinical trial (OVATION 3). The first patient was dosed in the Phase 3 study in the third quarter of 2025. IMNN-001 works by instructing the body to produce safe and durable levels of powerful cancer-fighting molecules, such as IL-12 and interferon gamma, at the tumor site. Additionally, the Company has completed dosing in a first-in-human study of its COVID-19 booster vaccine (IMNN-101).

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