Podcasts about PFS

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  • 209PODCASTS
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Best podcasts about PFS

Latest podcast episodes about PFS

Financial Sense(R) Newshour
Peter Zeihan Discusses His Latest Book, The End of the World Is Just the Beginning

Financial Sense(R) Newshour

Play Episode Listen Later Jul 1, 2022 70:26


Jul 1 – After this week's market wrap-up, Financial Sense Newshour speaks with the well-known geopolitical strategist Peter Zeihan to discuss his latest book, The End of the World Is Just the... Subscribe to our premium weekday podcasts: https://www.financialsense.com/subscribe

Mining Stock Daily
Why Demetri Kofinas Thinks the Fed will Sacrifice the Economy to Save Itself

Mining Stock Daily

Play Episode Listen Later Jul 1, 2022 63:40


Demetri Kofinas, host of the Hidden Forces podcast, joins us this week for a lengthy conversation centered on the months of interviews and content he's published recently on monetary and economic pivots. We talk about a few ideas some of his guests have shared, how its transformed his approach to markets, and why he's not going to questions the Fed's decisions to fight inflation. We'd like to thank our sponsors: Integra Resources is advancing the past-producing DeLamar Project in southwestern Idaho. The Company has continued to demonstrate resource growth and conversion through greenfield and brownfield exploration. Integra Resources trades on the TSX-V under ITR and the NYSE American under ITRG. Western Copper and Gold is focused on developing the world-class Casino project in Canada's Yukon Territory. The Casino project consists of an impressive 11 billion pounds of copper and 21 million ounces of gold in an overall resource. Western Copper and Gold trades on the TSX and the NYSE American with WRN. Be sure to follow the company via their website,www.westerncopperandgold.com. Rio-2 is advancing the Fenix Gold Project in Chile, the largest undeveloped gold heap leach project in the Americas. Fenix consists of 5 million ounces in the measured and indicated resource category and 1.4 million ounces in the inferred resource category. With a robust PFS in place, Fenix is set up for fast-tracked construction and production. You can find a list of project and company information on their website, rio2.com. ASCU is a Copper Mining Company with a 100% ownership of The Cactus Mine, located on private land in the Arizona Copper Belt. The Company is committed to supplying LME Grade A Copper Cathodes usable in the Renewable Energy Future, mined in a responsible and sustainable manner. Our goal, beyond our ESG Strategy, is to ensure “Net Zero Carbon Emission” from future operations, minimizing the effect of climate change on the earth and preserving our planet for our children and future generations. https://arizonasonoran.com/

Property and Freedom Podcast
PFP165 | David Dürr, “On How to Take the State to Court” (PFS 2016)

Property and Freedom Podcast

Play Episode Listen Later Jul 1, 2022


Property and Freedom Podcast, Episode 165. This talk is from the 2016 meeting of the Property and Freedom Society. David Dürr (Switzerland), On How to Take the State to Court. PFS 2016 Playlist.

Property and Freedom Podcast
PFP164 | Hans-Hermann Hoppe, Introductions, Day 3, Afternoon Sessions (PFS 2016)

Property and Freedom Podcast

Play Episode Listen Later Jul 1, 2022


Property and Freedom Podcast, Episode 164. This is Professor Hans-Hermann Hoppe‘s (Germany/Turkey) introduction before the afternoon sessions on Day 3 of the 2016 meeting of the Property and Freedom Society. PFS 2016 Playlist.

Financial Sense(R) Newshour
We've Entered a New Investment Regime, Says Alex Barrow; Gold Looking Attractive Again (Preview)

Financial Sense(R) Newshour

Play Episode Listen Later Jul 1, 2022 1:15


Jun 30 – Today, on FS Insider, our guest, Alex Barrow at Macro Ops, says they have been sitting in a large cash position since late last year when the market peaked and still think the market has... Subscribe to our premium weekday podcasts: https://www.financialsense.com/subscribe

Mining Stock Daily
Morning Briefing: Guanajuato Silver to Acquire Great Panther's Mexican Assets

Mining Stock Daily

Play Episode Listen Later Jun 30, 2022 9:15


Guanajuato Silver has signed a binding definitive agreement with Great Panther Mining. Adriatic Metals, Cornish Metals and Snowline Gold have new exploration updates to report today. We'd like to thank our sponsors: Integra Resources is advancing the past-producing DeLamar Project in southwestern Idaho. The Company has continued to demonstrate resource growth and conversion through greenfield and brownfield exploration. Integra Resources trades on the TSX-V under ITR and the NYSE American under ITRG. Western Copper and Gold is focused on developing the world-class Casino project in Canada's Yukon Territory. The Casino project consists of an impressive 11 billion pounds of copper and 21 million ounces of gold in an overall resource. Western Copper and Gold trades on the TSX and the NYSE American with WRN. Be sure to follow the company via their website,www.westerncopperandgold.com. Rio-2 is advancing the Fenix Gold Project in Chile, the largest undeveloped gold heap leach project in the Americas. Fenix consists of 5 million ounces in the measured and indicated resource category and 1.4 million ounces in the inferred resource category. With a robust PFS in place, Fenix is set up for fast-tracked construction and production. You can find a list of project and company information on their website, rio2.com. ASCU is a Copper Mining Company with a 100% ownership of The Cactus Mine, located on private land in the Arizona Copper Belt. The Company is committed to supplying LME Grade A Copper Cathodes usable in the Renewable Energy Future, mined in a responsible and sustainable manner. Our goal, beyond our ESG Strategy, is to ensure “Net Zero Carbon Emission” from future operations, minimizing the effect of climate change on the earth and preserving our planet for our children and future generations. https://arizonasonoran.com/

Property and Freedom Podcast
PFP163 | Hans Hermann Hoppe, “On The Ethics of Argumentation” (PFS 2016)

Property and Freedom Podcast

Play Episode Listen Later Jun 30, 2022


Property and Freedom Podcast, Episode 163. This talk is from the 2016 meeting of the Property and Freedom Society. Hans-Hermann Hoppe (Germany/Turkey), On the Ethics of Argumentation. Transcript below. PFS 2016 Playlist. Related: Kinsella's “Argumentation Ethics and Liberty: A Concise Guide,” Mises Daily (May 27, 2011). See youtube below: Hans-Hermann Hoppe The Ethics of Argumentation [Originally published at The […]

Financial Sense(R) Newshour
Manoj Pradhan on China, Deglobalization, and Structural Inflation (Preview)

Financial Sense(R) Newshour

Play Episode Listen Later Jun 30, 2022 2:03


Jun 29 – For multiple decades, the working age population of the globe experienced a dramatic expansion and lowered the cost of inflation for the cost of nearly every type of good, especially with... Subscribe to our premium weekday podcasts: https://www.financialsense.com/subscribe

Mining Stock Daily
Morning Briefing: Exploration Drill Results from Kodiak Copper, Calibre Mining, Goldshore and more

Mining Stock Daily

Play Episode Listen Later Jun 29, 2022 7:48


We have new drill results to report from Kodiak Copper, Calibre Mining, Goldshore Resources and Azimut. We'd like to thank our sponsors: Integra Resources is advancing the past-producing DeLamar Project in southwestern Idaho. The Company has continued to demonstrate resource growth and conversion through greenfield and brownfield exploration. Integra Resources trades on the TSX-V under ITR and the NYSE American under ITRG. Western Copper and Gold is focused on developing the world-class Casino project in Canada's Yukon Territory. The Casino project consists of an impressive 11 billion pounds of copper and 21 million ounces of gold in an overall resource. Western Copper and Gold trades on the TSX and the NYSE American with WRN. Be sure to follow the company via their website,www.westerncopperandgold.com. Rio-2 is advancing the Fenix Gold Project in Chile, the largest undeveloped gold heap leach project in the Americas. Fenix consists of 5 million ounces in the measured and indicated resource category and 1.4 million ounces in the inferred resource category. With a robust PFS in place, Fenix is set up for fast-tracked construction and production. You can find a list of project and company information on their website, rio2.com. ASCU is a Copper Mining Company with a 100% ownership of The Cactus Mine, located on private land in the Arizona Copper Belt. The Company is committed to supplying LME Grade A Copper Cathodes usable in the Renewable Energy Future, mined in a responsible and sustainable manner. Our goal, beyond our ESG Strategy, is to ensure “Net Zero Carbon Emission” from future operations, minimizing the effect of climate change on the earth and preserving our planet for our children and future generations. https://arizonasonoran.com/

Property and Freedom Podcast
PFP162 | Walter Block, “‘Market Failure'—Fact or Fiction?” (PFS 2016)

Property and Freedom Podcast

Play Episode Listen Later Jun 29, 2022


Property and Freedom Podcast, Episode 162. This talk is from the 2016 meeting of the Property and Freedom Society. Walter Block (USA), “Market Failure” – Fact or Fiction? PFS 2016 Playlist.

Property and Freedom Podcast
PFP161 | Hans-Hermann Hoppe, Introductions, Day 3, Morning Sessions (PFS 2016)

Property and Freedom Podcast

Play Episode Listen Later Jun 29, 2022


Property and Freedom Podcast, Episode 161. This is Professor Hans-Hermann Hoppe‘s (Germany/Turkey) introduction before the morning sessions on Day 3 of the 2016 meeting of the Property and Freedom Society. PFS 2016 Playlist.

Financial Sense(R) Newshour
Growth and Liquidity Indicators Still Pointing Down, Checklist for Market Bottom Far From Complete, Says VP's Aaran Param (Preview)

Financial Sense(R) Newshour

Play Episode Listen Later Jun 28, 2022 0:53


Jun 28 – Variant Perception's Aaran Param discusses the growth and liquidity outlook for the economy and markets and says that their leading indicators are still quite negative for the broad outlook.... Subscribe to our premium weekday podcasts: https://www.financialsense.com/subscribe

Mining Stock Daily
Morning Briefing: Western Copper and Gold Publish Feasibility Study for Casino

Mining Stock Daily

Play Episode Listen Later Jun 28, 2022 10:41


Western's Casino Project has a new full feasibility study out. Seabridge has a PFS for KSM out. We also have exploration updates to report from Meridian Mining, Royal Road, Lahontan Gold, Prospector Metals and AbraSilver. We'd like to thank our sponsors: Integra Resources is advancing the past-producing DeLamar Project in southwestern Idaho. The Company has continued to demonstrate resource growth and conversion through greenfield and brownfield exploration. Integra Resources trades on the TSX-V under ITR and the NYSE American under ITRG. Western Copper and Gold is focused on developing the world-class Casino project in Canada's Yukon Territory. The Casino project consists of an impressive 11 billion pounds of copper and 21 million ounces of gold in an overall resource. Western Copper and Gold trades on the TSX and the NYSE American with WRN. Be sure to follow the company via their website,www.westerncopperandgold.com. Rio-2 is advancing the Fenix Gold Project in Chile, the largest undeveloped gold heap leach project in the Americas. Fenix consists of 5 million ounces in the measured and indicated resource category and 1.4 million ounces in the inferred resource category. With a robust PFS in place, Fenix is set up for fast-tracked construction and production. You can find a list of project and company information on their website, rio2.com. ASCU is a Copper Mining Company with a 100% ownership of The Cactus Mine, located on private land in the Arizona Copper Belt. The Company is committed to supplying LME Grade A Copper Cathodes usable in the Renewable Energy Future, mined in a responsible and sustainable manner. Our goal, beyond our ESG Strategy, is to ensure “Net Zero Carbon Emission” from future operations, minimizing the effect of climate change on the earth and preserving our planet for our children and future generations. https://arizonasonoran.com/

Property and Freedom Podcast
PFP160 | Rindermann, Daniels, Schultze-Rhonhof, Stone: “Discussion—Q&A” (PFS 2016)

Property and Freedom Podcast

Play Episode Listen Later Jun 28, 2022


Property and Freedom Podcast, Episode 160. This panel discussion is from the 2016 meeting of the Property and Freedom Society. Heiner Rindermann (Germany), Gerd Schultze-Rhonhof (Germany), Anthony Daniels (Theodore Dalrymple) (England), Norman Stone† (UK/Turkey): “Discussion—Q&A”. PFS 2016 Playlist.

Financial Sense(R) Newshour
How Emotions and Politics Can Ruin Your Retirement Goals

Financial Sense(R) Newshour

Play Episode Listen Later Jun 28, 2022 48:34


Jun 27 – On today's Lifetime Planning episode, Jim Puplava and Josh Nunn discuss how to think of retirement planning as you would in running a business, why it's important to keep in mind the things... Subscribe to our premium weekday podcasts: https://www.financialsense.com/subscribe

ASCO Daily News
Novel Therapies in GI Oncology at ASCO22

ASCO Daily News

Play Episode Listen Later Jun 27, 2022 15:31


Dr. Rachna Shroff, of the University of Arizona Cancer Center, tells guest host, Dr. Shaalan Beg, of UT Southwestern's Harold C. Simmons Comprehensive Cancer Center and Science 37, about advances in precision medicine for pancreatic cancer featured at the 2022 ASCO Annual Meeting. She also highlights compelling new data from the FOLFOX, FOENIX-CCA2, and HERB trials in hepatocellular carcinoma, cholangiocarcinoma, and biliary tract cancer.   TRANSCRIPT Dr. Shaalan Beg: Hello and welcome to the ASCO Daily News podcast. I'm Dr. Shaalan Beg, your guest host of the ASCO Daily News podcast today. I'm an adjunct associate professor at UT Southwestern Simmons Comprehensive Cancer Center and vice president of oncology at Science 37. I'm delighted to welcome Dr. Rachna Shroff, the associate dean for clinical and translational research and the chief of gastrointestinal (GI) medical oncology at the University of Arizona Cancer Center where she's also the interim chief of Hematology-Oncology. Dr. Shroff is also the chair-elect for the Gastrointestinal Cancer Symposium. Today we'll be discussing key abstracts in GI cancer that were featured at the 2022 ASCO Annual Meeting. Our full disclosures are available in the show notes and disclosures of all our guests on the podcast can be found on our transcripts at asco.org/podcasts. Dr. Shroff, thank you for being on the podcast today. Dr. Rachna Shroff: Thank you so much for having me. Dr. Shaalan Beg: Let's begin by reviewing what is new in the realm of precision medicine in GI cancers. One of the diseases where precision medicine has not made adequate inroads is pancreatic cancer. One of the most common mutations in pancreas cancer is KRAS, but there haven't been a lot of treatments that can target the most common forms of KRAS. What did we hear at ASCO22 regarding precision medicine and pancreatic cancer? Dr. Rachna Shroff: I agree, I think that the area of precision oncology is, unfortunately, lagging behind a little bit in pancreatic cancer. But I think as we have gotten better and better with our comprehensive genomic profiling, we are identifying subsets of patients within pancreas cancer who are potentially amenable to targeted therapies. You already mentioned KRAS mutations, and we obviously have a number of inhibitors in development in that space, though, we are still missing that key G12D mutation that we see in pancreas cancer. But what I think was really interesting that came out of ASCO22, was a lot of interest and emphasis on better understanding the KRAS wild-type patients in pancreatic cancer. Now, this is obviously a smaller subset of patients, given that the majority of patients have KRAS mutations. But there was a really interesting abstract, LBA4011, that looked at patients with locally advanced or metastatic pancreatic cancer, who were KRAS wild-type. They actually received gemcitabine in combination with a monoclonal antibody targeting EGFR and nimotuzumab. This was a study that was done entirely in Asia. It involved 92 Chinese patients that were randomly assigned to receive the combination of nimotuzumab with gemcitabine. What was interesting in this study is that the patients were found in the full analysis set to have a significantly longer median overall survival of 10.9 months versus 8.5 months with a hazard ratio of 0.5. So, that of course was intriguing and provocative for sure. Similarly, the other endpoints were also somewhat intriguing in terms of improvements in the median progression-free survival (PFS), etc. And specifically, patients without biliary obstruction had a longer PFS, which was an interesting finding as well. The nimotuzumab overall was pretty well tolerated and not any sort of surprising treatment-related adverse events (TRAEs) were noted. And so, this is definitely a drug that, I think, piques our interest in terms of being able to target patients with KRAS wild-type pancreatic cancer. I think that questions, however, that remain, and I think require further study is really understanding what this drug could do in combination with the chemotherapy combinations that we use more frequently in metastatic pancreatic cancers such as gemcitabine and paclitaxel or 5FU-based regimens like FOLFIRINOX. I think given that it is a relatively well-tolerated drug, it would be a very reasonable thing to investigate this drug further in the KRAS wild-type population with the kind of modern-day chemotherapy regimens that we use. And I think, of course, we all know that it is useful to be able to look at these types of drugs in a more global population. And so, a larger patient set I think would be very useful as well, but at least it tells us that there is a way to think about our KRAS wild-type patients with pancreas cancer and that perhaps we really need to understand and identify those patients' potential for precision oncology. Dr. Shaalan Beg: One of the GI cancers that has been a hotbed for precision medicine is cholangiocarcinoma, a disease that's very close to your heart. What updates did we hear at ASCO22 regarding cholangiocarcinoma and precision medicine? Dr. Rachna Shroff: This space of targeted therapy and cholangiocarcinoma has been incredibly exciting for the last few years and I think drug development has been rapid-fire in that space. The oldest, if you will, target that we've been thinking about for some time is the FGFR2 fusion patient population. And in Abstract 4009 by Dr. Goyal and colleagues, we saw the results of the FOENIX-CCA 2 trial which was looking at an oral FGFR inhibitor (futibatinib) in patients with intrahepatic cholangiocarcinoma, who harbor FGFR2 fusions and gene rearrangements. We had initially seen some of this data presented a few years back, but this was the updated data set. It was a single-arm phase 2 study that involved patients with advanced intrahepatic cholangiocarcinoma who had identified FGFR2 gene fusions, and they received futibatinib daily until progression. This was a traditional single-arm phase 2 study with a primary endpoint of overall response rate. At the final data cut, with a median follow-up of 25 months, there's actually a confirmed overall response rate of 41.7%. And I think that what was really exciting about this is this is a refractory patient population. So, in patients who have refractory cholangiocarcinoma, the other drugs, the non-targeted therapy drugs that we think through, really have response rates more in the single-digit to 10% range and so to have a confirmed overall response (OR) over 40% is truly exciting. The duration of the response was also exciting. This is not just a drug that works briefly, it has a duration of response of 9.5 months. And the mature median overall survival was 20 months. And in a disease which we talk about with the ABC-02 data of GemCis, a median OS in advanced disease of 11.7 months. This is really, really exciting for patients who harbor this fusion or gene rearrangement. We know that that's seen in about 10 to 15% of patients. So, again, we're dealing with a smaller subset, but it clearly demonstrates the need to identify FGFR2 gene fusions, so that we can offer these types of targeted therapies. This was not the first FGFR inhibitor that we have seen data on and in fact, we have 2 drugs already U.S. Food and Drug Administration (FDA) approved. And so, when we look at the common treatment-related adverse events that were identified with the futibatinib, there are really class effects related to FGFR inhibition like hyperphosphatemia, alopecia, dry mouth, nothing that really stood out or that was concerning. And so, I think this final analysis for the FOENIX study really just reaffirms the utility of futibatinib in patients with FGFR2 gene fusions, and the mature OS data, the duration of response, all of this really aligns with the need to identify patients with this alteration so that we can, post-gemcitabine based therapies, offer this targeted therapy or an FGFR inhibitor in general to these patients. I think the other really exciting abstract in the glandular carcinoma or biliary tract cancer space was Abstract 4006. This was the updated data from the HERB trial, which was an investigator-initiated multicenter phase 2 trial looking at trastuzumab deruxtecan (T-DXd) in patients who have HER2 expressing unresectable or recurrent biliary tract cancer. Trastuzumab deruxtecan, I'm sure everybody has been hearing about because it has been incredibly effective in HER2 alterations across a myriad of different disease sites. And so, not wanting to be left out, biliary tract cancers were investigated in this study with patients who had HER2 expression, so, that was HER2-positive IHC3+ or IHC2+/ISH+, and they also looked at HER2-low expressing patients, and [whose disease] were refractory or intolerant to gemcitabine-based therapy with the primary endpoint of overall response rate. So, in the HERB trial, a total of 32 patients were enrolled. 24 of them were HER2-positive and 8 were HER2-low and they all received trastuzumab deruxtecan. When you look at the efficacy data, the confirmed overall response rate in the patients with HER2-positive was 36.4%, which again, as I said, in a refractory patient population is certainly very exciting data. And the overall disease control median, PFS, and median OS were all pretty encouraging in terms of efficacy. What was also kind of intriguing was that there was some efficacy seen even in the patients who are HER2-low. Now, this is, in my opinion, a slightly less exciting amount of efficacy, but still important to note that the overall response rate in HER2-low was 12.5% with a median PFS that was also somewhat exciting at 4.2 months. And so, there is a potential clearly for targeting patients with HER2-high or HER2-positive with trastuzumab deruxtecan, and I think in the patients who are HER2-low, we need to better understand the potential utility. The common treatment-related adverse events that we see were the typical things that we've heard about with trastuzumab deruxtecan, but I think the one thing that was really worth noting was 8 patients or 25% of patients had interstitial lung disease (ILD), which we know is an important identified safety concern for patients who receive trastuzumab deruxtecan, and I think that's a pretty sizable number of 25%, so, I think that's going to really require a little bit more fleshing out for us to understand the safety for these patients. One question that a lot of us have had is whether these are patients who have received gemcitabine, which we know can also cause pneumonitis. And so, I don't know if we're seeing a higher percentage of ILD because of, 'priming' with prior gemcitabine. But regardless, I think this is just proof of principle that again, we need to identify patients with biliary tract cancers that have HER2-positivity because we now have a number of drugs including potentially trastuzamab deruxtecan to target [their disease] with after gemcitabine-based treatments Dr. Shaalan Beg: Absolutely. Any new biomarkers to keep on the radar for our listeners? Dr. Rachna Shroff: I think there are a lot of really exciting targets. One that was talked about and that we saw data on at ASCO [Annual Meeting] was from Abstract 4048, which looked at claudin [18]. Claudin is basically a transmembrane protein that kind of helps maintain the tight junctions between cells. In gastric cancer, in particular, we look at claudin 18 isoform 2, and there are 18.1 and 18.2 gene expressions that have been identified in gastric cancer. So, there was a very comprehensive abstract that was presented of over 1,900 samples that underwent comprehensive profiling by next-generation sequencing. And the patients were identified with claudin 18.1, and 18.2, high versus low. Claudin 18.2 expression was actually detected in 97% of the samples. It's slightly lower with claudin 18.1 at 63%. It's important to note that the primary tumors had higher expression levels than the metastatic tumors, so those were really the tumors in which they did a deeper dive. And in the process of doing this deeper dive, they did a really interesting kind of better understanding of the immune microenvironment and the immune profile in the samples that had claudin expression. And what was identified is that there was an inverse relationship basically between claudin 18.1 and 18.2 expression and correlation with PD-L1 positivity, tumor mutational burden (TMB)-high, M1 macrophages expression, NK cell presence, CD4 positive T-cells, myeloid dendritic cells. And so, there's clearly something between the presence of this claudin expression and the effect it has on the immune microenvironment. I think that's very relevant to keep in mind because as we all know, there's a whole space of drug development focused right now on anti-claudin 18.2 monoclonal antibodies, as well as a target for antibody-drug conjugates (ADC) and cellular therapies with CAR T-cell therapies being developed specifically against claudin 18. And so, understanding the immune microenvironment and the interaction between the claudin expression will be really important as we continue to charge forward in that space. Dr. Shaalan Beg: Absolutely. Very, very exciting. Sticking with the liver pancreas theme, what other studies piqued your interest with regards to hepatocellular carcinoma (HCC)? Dr. Rachna Shroff: It's a really exciting time in HCC. I mean, we actually have drugs that are working in the advanced space. And so, now there's a lot of interest in shifting to looking at preoperative neoadjuvant, and adjuvant approaches and what we can do to improve disease-free survival and overall survival in patients who are able to undergo prior resection. So, Abstract 4013 looked specifically at the efficacy and safety of adjuvant hepatic arterial infusion chemotherapy with FOLFOX. And this was a randomized open-label phase 3 trial. It actually included a total of 315 patients between 5 different centers and patients were randomly assigned to receive either 1 to 2 cycles of adjuvant HAIC FOLFOX (Hepatic Arterial Infusion Chemotherapy FOLFOX) versus just follow up, the control group had no adjuvant treatment, and the primary endpoint was disease-free survival here and in the intention to treat population, there was a significantly improved median disease-free survival at 27 months versus 11 months in the patients who were on the control arm. And there was a protocol analysis, there were a number of other efficacy endpoints including disease-free survival rates at 1, 2, and 3 years. And everything kind of leaned towards and or suggested an improvement with the utility of HAI FOLFOX in patients who undergo complete resection. It should be noted that this included patients specifically who had microvascular invasion on their resection. And so, these are patients who are at higher risk for recurrence as we know. This to me suggests that there could be a role for adjuvant treatment in patients who undergo complete resection with microvascular invasion (MVI). HAI is a very specific technique and it requires a highly skilled center in the placement of HAI pumps. And we're seeing more and more trials across the U.S. as well investigating the role of HAI in advanced disease and in perioperative approaches. And so, I think this is an area of much-needed continued research. There are, of course, a number of ongoing adjuvant studies looking at immunotherapy in the adjuvant setting. And so, it'll be really important to see how those read out and then to try to put all of these in context so that we can better understand local therapy like HAI FOLFOX versus more systemic adjuvant approaches like immunotherapy. Dr. Shaalan Beg: Thank you very much, Dr. Shroff for sharing your valuable insights with us. I really appreciate you taking the time to spend with us and our listeners. Dr. Rachna Shroff: Thanks so much. I enjoyed it. Dr. Shaalan Beg: And thank you to our listeners for your time today. You will find links to the abstracts discussed today in the transcript of this episode. Finally, we'd really like to hear your feedback. If you could please take a moment to rate, review, and subscribe wherever you get your podcasts. Thank you very much!   Disclosures: Dr. Shaalan Beg: Employment: Science 37 Consulting or Advisory Role: Ipsen, Array BioPharma, AstraZeneca/MedImmune, Cancer Commons, Legend Biotech, Foundation Medicine Research Funding (Inst.): Bristol-Myers Squibb, AstraZeneca/MedImmune, Merck Serono, Five Prime Therapeutics, MedImmune, Genentech, Immunesensor, Tolero Pharmaceuticals Dr. Rachna Shroff: Consulting or Advisory Role: Exelixis, Merck, QED Therapeutics, Incyte, Astra Zeneca, Taiho Pharmaceutical, Boehringer Ingelheim, SERVIER, Genentech, Basilea Research Funding: Pieris Pharmaceuticals, Taiho Pharmaceutical, Merck, Exelixis, QED Therapeutics, Rafael Pharmaceuticals, Bristol-Myers Squibb, Bayer, Immunovaccine, Seagen, Novocure, Nucana, Loxo/Lilly, Faeth Therapeutics Disclaimer: The purpose of this podcast is to educate and inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. 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.  

OUTTAKE VOICES™ (Interviews)
LGBTQ Filmmakers, Honorees & Allies

OUTTAKE VOICES™ (Interviews)

Play Episode Listen Later Jun 27, 2022 19:14


Veteran filmmakers, honorees and activists Dale Dickie, Jean Carlomusto, Esther Newton and Jay Critchley talk with  Emmy Winner Charlotte Robinson host of OUTTAKE VOICES™ at the 24th annual Provincetown International Film Festival (PIFF) press luncheon that took place at Lands End Inn Provincetown, Massachusetts. First we spoke with actress Dale Dickie who was being honored with PIFF's 2022 Excellence in Acting Award. Dale is a superbly talented veteran of film, television and the theater with over 60 film credits. Dale talked about her leading role in the feature film “A Love Song” that premiered at Sundance and won the John Schlesinger Narrative Award at PIFF. “A Love Song” is about two childhood sweethearts Faye (Dale Dickie) and Lito (Wes Studi) now both widowed who share a night by a lake in the mountains. Reuniting after 40 years the pair share childhood memories make small talk and shelter together from loneliness. Dale a fierce LGBTQ ally also addressed our LGBTQ issues and her own survival in the entertainment industry. Then we chatted with director Jean Carlomusto a filmmaker, activist and interactive media artist whose film “Esther Newton Made Me Gay” made its North American Premiere at the festival and won the Warner Bros. Discovery Audience Award / Best Documentary Feature at PIFF. She was joined by the subject of her film anthropologist and author Esther Newton who throughout her career has questioned and challenged the status quo on gender, sexuality and anthropological methods. Her work has inspired generations of scholars to pursue research in what would eventually become the field of LGBTQ and Gender Studies. Esther talked about her work and what she hopes the film will accomplish and then gave us her spin on our LGBTQ issues. We concluded our montage with Jay Critchley a visual, conceptual and performance artist whose work and environmental activism has traversed the globe. Jay was honored in 2017 for his commitment to PIFF and to Provincetown. Jay's 2022 PIFF short film selection “Cheeky: Not For Tea Dance” edited by Vanessa Vartabedian can be viewed virtually at PIFF now through June 26th.   The Provincetown Film Society (PFS), which began as the Provincetown International Film Festival in 1999 is a non-profit arts organization dedicated to showcasing new achievements in independent film and honoring the work of emerging as well as acclaimed directors, producers and actors. Their mission is articulated through three primary activities: the annual Provincetown International Film Festival (PIFF), their year-round theater operation of the Water's Edge Cinema and the Gabrielle A. Hanna Provincetown Film Institute for film and media artist residencies and conferences. As a substantial contributor to the economic and creative vitality of America's oldest art colony PFS is dedicated to becoming a sustainable year-round cultural organization that brings film education, genre-specific festivals and cultural partnerships to the outer Cape.    For More Info…   LISTEN: 600+ LGBTQ Chats @OUTTAKE VOICES

Mining Stock Daily
Morning Briefing: Calibre Mining hits Bonanza Grade

Mining Stock Daily

Play Episode Listen Later Jun 27, 2022 9:18


There are new drill results from Calibre Mining, Roscan Gold, GCM Mining, Canada Nickel and Baselode Energy to report today We'd like to thank our sponsors: Integra Resources is advancing the past-producing DeLamar Project in southwestern Idaho. The Company has continued to demonstrate resource growth and conversion through greenfield and brownfield exploration. Integra Resources trades on the TSX-V under ITR and the NYSE American under ITRG. Western Copper and Gold is focused on developing the world-class Casino project in Canada's Yukon Territory. The Casino project consists of an impressive 11 billion pounds of copper and 21 million ounces of gold in an overall resource. Western Copper and Gold trades on the TSX and the NYSE American with WRN. Be sure to follow the company via their website,www.westerncopperandgold.com. Rio-2 is advancing the Fenix Gold Project in Chile, the largest undeveloped gold heap leach project in the Americas. Fenix consists of 5 million ounces in the measured and indicated resource category and 1.4 million ounces in the inferred resource category. With a robust PFS in place, Fenix is set up for fast-tracked construction and production. You can find a list of project and company information on their website, rio2.com. ASCU is a Copper Mining Company with a 100% ownership of The Cactus Mine, located on private land in the Arizona Copper Belt. The Company is committed to supplying LME Grade A Copper Cathodes usable in the Renewable Energy Future, mined in a responsible and sustainable manner. Our goal, beyond our ESG Strategy, is to ensure “Net Zero Carbon Emission” from future operations, minimizing the effect of climate change on the earth and preserving our planet for our children and future generations. https://arizonasonoran.com/

Property and Freedom Podcast
PFP159 | Norman Stone, “On Politics and Religion” (PFS 2016)

Property and Freedom Podcast

Play Episode Listen Later Jun 27, 2022


Property and Freedom Podcast, Episode 159. This talk is from the 2016 meeting of the Property and Freedom Society. Norman Stone† (UK/Turkey), On Politics and Religion. PFS 2016 Playlist.

Clinical Papers Podcast
#108 - DESTINY-Breast04: Trastuzumab Deruxtecan em pacientes com câncer de mama avançado HER2 "Low"

Clinical Papers Podcast

Play Episode Listen Later Jun 24, 2022 32:00


O DESTINY-Breast04 é o primeiro RCT a benefícios clinicamente significativos para pacientes com câncer de mama metastático HER2 low.Como regra geral, pacientes com câncer de mama avançado e baixos níveis de expressão de HER2 (HER2 low) são considerados como HER2-negativos porque as terapias direcionadas a HER2 geralmente se mostram ineficazes nesse cenário. O DESTINY-Breast04 quebra esse paradigma, abrindo as portas para uma nova opção de tratamento para esses pacientes.Com um seguimento mediano de 18,4 meses, o braço T-DXd reduziu em 50% o PFS (9,9 vs 5,1 meses; HR 0,50, IC 95% [0,40, 0,63]; P

Financial Sense(R) Newshour
Jim Steffens: Diesel Fuel Inventory a Big National Security Situation

Financial Sense(R) Newshour

Play Episode Listen Later Jun 24, 2022 41:42


Jun 24 – Is inflation under control? Are more rate hikes ahead? Joining us on the Financial Sense Newshour is Craig "Bullseye" Johnson of Piper Jaffray . Craig thinks we have not yet hit market lows... Subscribe to our premium weekday podcasts: https://www.financialsense.com/subscribe

Financial Sense(R) Newshour
Dan Steffens: Diesel Fuel Inventory a Big National Security Situation

Financial Sense(R) Newshour

Play Episode Listen Later Jun 24, 2022 41:42


Jun 24 – Is inflation under control? Are more rate hikes ahead? Joining us on the Financial Sense Newshour is Craig "Bullseye" Johnson of Piper Jaffray . Craig thinks we have not yet hit market lows... Subscribe to our premium weekday podcasts: https://www.financialsense.com/subscribe

Mining Stock Daily
Chris Temple: When the Fed Reverses Course, It will be too Late

Mining Stock Daily

Play Episode Listen Later Jun 24, 2022 53:24


In this week's long-form we reconnect with Chris Temple, publisher of the National Investor. We have a wide range of topics to get through in this discussion, including soft landings in the stock market, holes in the economy beginning to percolate, a void of an energy policy, and the summer doldrums of junior mining. We'd like to thank our sponsors: Integra Resources is advancing the past-producing DeLamar Project in southwestern Idaho. The Company has continued to demonstrate resource growth and conversion through greenfield and brownfield exploration. Integra Resources trades on the TSX-V under ITR and the NYSE American under ITRG. Western Copper and Gold is focused on developing the world-class Casino project in Canada's Yukon Territory. The Casino project consists of an impressive 11 billion pounds of copper and 21 million ounces of gold in an overall resource. Western Copper and Gold trades on the TSX and the NYSE American with WRN. Be sure to follow the company via their website,www.westerncopperandgold.com. Rio-2 is advancing the Fenix Gold Project in Chile, the largest undeveloped gold heap leach project in the Americas. Fenix consists of 5 million ounces in the measured and indicated resource category and 1.4 million ounces in the inferred resource category. With a robust PFS in place, Fenix is set up for fast-tracked construction and production. You can find a list of project and company information on their website, rio2.com. ASCU is a Copper Mining Company with a 100% ownership of The Cactus Mine, located on private land in the Arizona Copper Belt. The Company is committed to supplying LME Grade A Copper Cathodes usable in the Renewable Energy Future, mined in a responsible and sustainable manner. Our goal, beyond our ESG Strategy, is to ensure “Net Zero Carbon Emission” from future operations, minimizing the effect of climate change on the earth and preserving our planet for our children and future generations. https://arizonasonoran.com/

Property and Freedom Podcast
PFP158 | Anthony Daniels (Theodore Dalrymple), “On Bogus Illnesses and Their Enablers” (PFS 2016)

Property and Freedom Podcast

Play Episode Listen Later Jun 24, 2022


Property and Freedom Podcast, Episode 158. This talk is from the 2016 meeting of the Property and Freedom Society. Anthony Daniels (Theodore Dalrymple) (England), “On Bogus Illnesses and Their Enablers”. PFS 2016 Playlist.

American Institute of CPAs - Personal Financial Planning (PFP)
Deeper CPA financial planner connections with Akemi Dalvi {PFP Section}

American Institute of CPAs - Personal Financial Planning (PFP)

Play Episode Listen Later Jun 24, 2022 26:25


Akemi Dalvi, CPA/PFS, began her career working in audit at PwC. She loved the idea of working more intimately with clients, so she took her dad's offer to join his financial planning business in 2008 and has since taken over as President. In this episode of the PFP Section podcast, Lyle Benson, CPA/PFS, interviews Akemi. She responds to the following questions: How did she create a niche practice to serve Japanese Americans? How did the pandemic lead to endless possibilities for attracting and retaining clients and staff? What allows her to spend her time on what she loves most? How does she build her knowledge and community of other advisors? What do her clients find most valuable about her service offering? Access resources related to this podcast: Note: If you're using a podcast app that does not hyperlink to the resources, visit http://pfplanning.libsyn.com/ to access show notes with direct links.  PFP and PFS members can get a taste of what the PFP Summit community is all about by joining us for a one-hour discussion on June 29th from 1 to 2 pm ET. Cameron Passmore and Jean-Luc Bourdon, CPA/PFS, will share their experiences with having client conversations about their personal finances in times of high inflation, rising interest rates, stock market volatility, and geopolitical uncertainty. 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 at www.aicpa.org/pfp 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.

Mining Stock Daily
Morning Briefing: New Drill Results from Arizona Sonoran, Patriot Battery Metals and more

Mining Stock Daily

Play Episode Listen Later Jun 23, 2022 9:40


We have new drill results to report from Arizona Sonoran Copper, Patriot Battery Metals, and Emerita Resources. Ascot provided a lengthy update on construction, financing and exploration work at Premier. Minera Alamos reports on some early exploration work at Cerro de Oro. We'd like to thank our sponsors: Integra Resources is advancing the past-producing DeLamar Project in southwestern Idaho. The Company has continued to demonstrate resource growth and conversion through greenfield and brownfield exploration. Integra Resources trades on the TSX-V under ITR and the NYSE American under ITRG. Western Copper and Gold is focused on developing the world-class Casino project in Canada's Yukon Territory. The Casino project consists of an impressive 11 billion pounds of copper and 21 million ounces of gold in an overall resource. Western Copper and Gold trades on the TSX and the NYSE American with WRN. Be sure to follow the company via their website,www.westerncopperandgold.com. Rio-2 is advancing the Fenix Gold Project in Chile, the largest undeveloped gold heap leach project in the Americas. Fenix consists of 5 million ounces in the measured and indicated resource category and 1.4 million ounces in the inferred resource category. With a robust PFS in place, Fenix is set up for fast-tracked construction and production. You can find a list of project and company information on their website, rio2.com. ASCU is a Copper Mining Company with a 100% ownership of The Cactus Mine, located on private land in the Arizona Copper Belt. The Company is committed to supplying LME Grade A Copper Cathodes usable in the Renewable Energy Future, mined in a responsible and sustainable manner. Our goal, beyond our ESG Strategy, is to ensure “Net Zero Carbon Emission” from future operations, minimizing the effect of climate change on the earth and preserving our planet for our children and future generations. https://arizonasonoran.com/

Mining Stock Daily
Morning Briefing: Collective Mining Makes New Discovery in Colombia

Mining Stock Daily

Play Episode Listen Later Jun 22, 2022 8:59


Collective Mining announced the discovery of a new copper-gold-silver porphyry-related breccia at the Guayabales project. B2Gold has new drill results out of Mali. Calibre Mining provided a multi-year outlook of its forecast gold production. Alexco provided an update on operations today for its Keno Hill Silver District in Yukon. We'd like to thank our sponsors: Integra Resources is advancing the past-producing DeLamar Project in southwestern Idaho. The Company has continued to demonstrate resource growth and conversion through greenfield and brownfield exploration. Integra Resources trades on the TSX-V under ITR and the NYSE American under ITRG. Western Copper and Gold is focused on developing the world-class Casino project in Canada's Yukon Territory. The Casino project consists of an impressive 11 billion pounds of copper and 21 million ounces of gold in an overall resource. Western Copper and Gold trades on the TSX and the NYSE American with WRN. Be sure to follow the company via their website,www.westerncopperandgold.com. Rio-2 is advancing the Fenix Gold Project in Chile, the largest undeveloped gold heap leach project in the Americas. Fenix consists of 5 million ounces in the measured and indicated resource category and 1.4 million ounces in the inferred resource category. With a robust PFS in place, Fenix is set up for fast-tracked construction and production. You can find a list of project and company information on their website, rio2.com. ASCU is a Copper Mining Company with a 100% ownership of The Cactus Mine, located on private land in the Arizona Copper Belt. The Company is committed to supplying LME Grade A Copper Cathodes usable in the Renewable Energy Future, mined in a responsible and sustainable manner. Our goal, beyond our ESG Strategy, is to ensure “Net Zero Carbon Emission” from future operations, minimizing the effect of climate change on the earth and preserving our planet for our children and future generations. https://arizonasonoran.com/

Property and Freedom Podcast
PFP155 | Heiner Rindermann, “Cognitive and Cultural ‘Enrichment' of Europe by Immigration” (PFS 2016)

Property and Freedom Podcast

Play Episode Listen Later Jun 22, 2022


Property and Freedom Podcast, Episode 155. This talk is from the 2016 meeting of the Property and Freedom Society. Heiner Rindermann (Germany), “Cognitive and Cultural ‘Enrichment' of Europe by Immigration”. PFS 2016 Playlist.

ASCO Daily News
DESTINY-Breast04 and Other Key Breast Cancer Studies at ASCO22

ASCO Daily News

Play Episode Listen Later Jun 21, 2022 31:01


Dr. Allison Zibelli, of the Sidney Kimmel Cancer Center – Jefferson Health, and Dr. Hope Rugo, of the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, discuss the practice-changing DESTINY-Breast04 trial as well as novel therapies in metastatic HR+/HER2- breast cancer from the TROPiCS-02 and MAINTAIN studies, all of which were featured at the 2022 ASCO Annual Meeting.   TRANSCRIPT Dr. Allison Zibelli: Hello. I'm Dr. Allison Zibelli, your host for the ASCO Daily News Podcast today. I'm a vice-chair and breast medical oncologist at the Sidney Kimmel Cancer Center, Jefferson Health in Philadelphia. My guest today is Dr. Hope Rugo, a professor of medicine and the director of Breast Oncology and Clinical Trials Education at the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco. We'll be discussing key advances in breast cancer that were featured at the 2022 ASCO Annual Meeting. Our full disclosures are available in the show notes, and disclosures of all guests on the podcasts can be found on our transcripts at asco.org/podcasts. Hope, it's great to talk to you today. Dr. Hope Rugo: Nice to talk to you, too. Dr. Allison Zibelli: Let's begin with perhaps the most exciting abstract at ASCO this year, which was the DESTINY-Breast04 study, that's LBA3, a randomized phase 3 study of trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-low, unresectable and/or metastatic breast cancer. What are your thoughts about this study? Dr. Hope Rugo: Well, of course, this is a hugely practice-changing study as was noted in the second-to-last slide by the discussant [Dr.] Pat LoRusso. So, antibody-drug conjugates are really the next step in delivering chemotherapy to cancer cells. The antibody-drug conjugates allow targeted delivery of a toxin to the cancer cell. I think we didn't understand how important this was going to be. These second, sort of, verging on third-generation antibody-drug conjugates use an antibody approach and to then have a new generation of linkers, which allow the drug to be released locally, but to then have drugs which pack a big bang for the buck. So, the way antibody-drug conjugates are constructed, you need to have a drug that actually can't be given as a naked drug because it's too toxic because you're giving just very small amounts of this drug that are delivered directly to the cancer cell. And the other really critical part of this is that the drug-to-antibody ratio of at least the successful and new antibody-drug conjugates (ADC) is quite high in the 7.5 to 8 toxins per antibody. Now, what that's resulted in is really interesting, is that there's a bystander effect. So, the toxin itself can leak out of the cancer cell that it's targeted and kill neighboring cells, but also because of the construct of these antibody-drug conjugates, what's likely happening is even if the cancer cell's a very low expression of the target, really low, you're able to actually get that ADC into the cancer cell to kill the cancer cell. So that may be a big part of the so-called bystander effect. So trastuzumab deruxtecan is biosimilar trastuzumab linked to a topoisomerase inhibitor deruxtecan, and what happened here was that of course, we saw remarkable data in HER2+ disease, unbelievable p-values in DESTINY-Breast03 compared to T-DM1, a first-generation ADC. But in DESTINY-Breast04, we targeted a population of patients largely with hormone receptor-positive disease who had a little expression of HER2, 1 plus or 2 plus by immunohistochemistry and no gene amplification. And this trial, which randomly assigned patients 2:1 and included just 58 patients with triple-negative disease. So in this trial, 480 had hormone receptor-positive breast cancer, a median of 1 line of prior chemotherapy. They were only allowed up to 2. They were refractory to endocrine therapy, a median of 3 lines of endocrine therapy. In the overall patients and in the hormone receptor-positive patients, there was actually a doubling in progression-free survival (PFS). It started very early, and it continued throughout, and at every landmark analysis, T-DXd was better than the treatment of physician choice that patients were randomly assigned to. It's also important when you're thinking about trials like this to think about what the treatment of physician choice was, and it was all chemotherapy regimens we would use. Paclitaxel, nab-paclitaxel, capecitabine, eribulin, or gemcitabine. And, so, I think that that doesn't bring up any questions. When they looked at the hormone receptor-positive group, they saw, if anything, even a bigger benefit overall. Now, the other endpoint of this trial was overall survival, and at this first analysis, they saw an improvement in overall survival that was quite dramatic. The absolute difference was 6.4 months, which is pretty amazing for an overall survival difference. And then they looked at this exploratory endpoint at the 58 patients who were valuable at triple-negative breast cancer, and then that group of patients, also saw an improvement in PFS of 5.6 months, an improvement in overall survival of 9.9 months, very small group, but amazing data. The forest plots are exactly what you want to see, all the dots line up to the left of 1, and overall responses improved. One of the concerns with this drug has been toxicity. The toxicity showed no new toxicity signals, which is really important. Nausea is the biggest issue that we deal with. It's mostly grade 1 and 2, but still something that's important to manage. A little bit of hair loss, not much in the way of bone marrow suppression, which is interesting. Interstitial lung disease (ILD) or pneumonitis continues to be an important issue to follow. 12% of patients had ILD of any grade. Most of it was grade 1 and 2, but 3 patients died, representing 0.8%. So, this really highlights the importance of monitoring and managing pneumonitis. Regardless of that, few patients had a reduced ejection fraction, but again, very, in general, low grade. This is really a new standard of care, and the standing ovation was really due to the fact that all we do is dedicate ourselves to trying to help patients live longer and better with their cancers, and in this trial, we have a huge win that has no qualifications. We can help patients not only control their disease longer but live longer with T-Dxd compared to standard chemotherapy. Dr. Allison Zibelli: So, Hope, I know as a practicing medical oncologist, I find that our metastatic triple-negative patients are often the biggest therapeutic challenges for us. Will they be doing larger studies with these patients that are HER2-low? Dr. Hope Rugo: It's a really good point. About 65% of patients with hormone receptor-positive disease or so-called HER2-low, centrally confirmed in the study. So, a fair number of people, about a quarter, did not have HER2-low disease when they were tested centrally. In the triple-negative population, who really are ER, PR, HER2- by standard definitions, about a third of the patients might have HER2-low disease. So, there's a lot of interest in further exploring that and looking at the patients who have ultra-HER2-low disease, so between and 1 plus a little bit of expression. That's been studied in the hormone receptor-positive population in DESTINY-Breast06. But there's a lot of interesting further defining that triple-negative population, so to speak, they're going to be triple-negative plus now and understanding what the benefit is in that population. So definitely will be looked at more now moving forward. Dr. Allison Zibelli: Thank you. So, let's move on to Abstract 1002. And the results from the phase 1, 2 study of patritumab deruxtecan, a HER3-directed antibody-drug conjugate, and patients with HER3 expressing metastatic breast cancer. What are your thoughts about this study? Dr. Hope Rugo: That's a really interesting, another one of these second- to third-generation antibody-drug conjugates. It's just the antibody, instead of being the usual, sort of, HER2 or TROP2 that we're used to thinking about is directed to HER3, 1 of the HER family of proteins. This is interesting. There's actually been a lot of work trying to target HER3 with naked antibodies with disappointing results, although I have to say most of the studies really didn't push it too far. So, with this antibody drug construct, deruxtecan, which is the same as in T-DXd and another TROP2 ADC Dato-DXd is used. So, I will say they do need to change the toxin in the next generation of ADCs. But they looked at, at first did a dose-finding study which has previously been presented, and then a dose expansion in both hormone receptor-positive HER2-negative disease and triple-negative disease. All the triple-negative patients had HER3 high disease by immunohistochemistry, and the hormone-receptor-positive patients were enrolled in 2 cohorts, HER3 high and HER3 low. And the median number of prior treatment regimens that patients had received in the hormone-receptor-positive group was 6 and 2 for the triple-negative group, but there was a huge range, up to 13 lines of treatment. They only had 14 patients with HER2+ disease. So, it's a little bit hard to know what to do with that patient group, but they were heavily pretreated 5.5 prior lines of therapy. The confirmed overall response rate in the 113 patients with combined HER3 high and low was 30%, very impressive, heavily pretreated patients. For triple-negative disease all HER3 high, it was 23%. Again, very nice. And there were 14 patients with HER2+ disease that also were HER3 high. It was about 43%. So those are nice responses, but we always want to know how durable is that. The duration of response ranged from 6 to over 8 months in those 3 different groups. So, these were quite durable. It wasn't any 2- to 3-month duration of response. So very impressive. And then when they looked to see, did it matter whether you had HER3 expression that was high or low in the hormone-receptor positive group, they actually did see responses in the HER3-low group, some very good responses. Overall, there were less patients in that group, but it does suggest that maybe you would still see responses in the HER3-low group, very impressive. And then 1 really interesting correlative study they did was they looked to see what happened to the HER3 expression on the tumor cell over time, and it went down. So, you treated the HER3 expression in most of the patients just dropped off completely, which is really interesting. It didn't have any association with clinical activity, but it's sort of an interesting correlative endpoint. This is a drug that overall was pretty well tolerated. They saw a similar toxicity to T-DXd with a lot of nauseous, a little bit of alopecia, a little bit more bone marrow suppression than we're used to seeing with T-DXd. So, neutropenia was seen in about 10% of patients at the lower dose and about a quarter of the patients at the higher dose. Overall, pretty well tolerated. Now, interstitial lung disease is a toxicity with this construct, and they saw ILD of 7% but most cases were grade 1 and 2. The other interesting toxicity that's unique to this agent is thrombocytopenia. So, they saw a grade 3 or greater rate of thrombocytopenia of 27% in the lower dose group, and in the larger group that received the higher dose, 39% of grade 3 or greater thrombocytopenia, so platelets less than 100,000. Turns out that when you stop the drug, the platelets do come back, so that's a good thing. Sometimes we saw long-term thrombocytopenia with T-DM1. They didn't see bad toxicity like bleeding, but it is something that needs to be managed with this drug because we're not great at managing thrombocytopenia. In any case, it has fast-track designation for another solid tumor, not breast cancer, and we'll have to see where this fits into our dizzying array of very effective ADCs now. Dr. Allison Zibelli: The practicing medical oncologist is not used to testing for HER3 in our patients with breast cancer. How common is it? Dr. Hope Rugo: HER3 expression is quite common in hormone receptor-positive disease, a little less common in triple-negative breast cancer. So, I think that we would see expression if we were going to be treating patients with this particular approach. Dr. Allison Zibelli: All right. Let's move on to Abstract 507, which reported long-term outcomes of adjuvant denosumab in breast cancer, specifically fracture reduction and survival results from 3,425 patients in a randomized double-blind, placebo-controlled ABCSG-18 trial. What are your thoughts about this study? Dr. Hope Rugo: Well, this trial, this is an update of a study that previously has been presented and published, most recent publication was in Lancet Oncology in 2019, and these patients were randomly assigned to receive denosumab at 60 milligrams, important to note the dose, subcutaneously every 6 months versus placebo every 6 months, and they did get placebo subcutaneous injections. And this treatment continued through their endocrine therapy. They showed a dramatic reduction in fracture rate, and that has been maintained over time. We were really surprised enough to suggest that maybe Austrian people didn't go into the sun, so they got more Vitamin D deficiency, hard to know, but the hazard ratio is 0.5. It's unbelievable the number of fractures, 92 for denosumab but 176 for placebo, a P value of less than .0001. So, this is a real endpoint, treating patients who are receiving endocrine therapy that, in this case, non-steroidal aromatase inhibitor therapy that can increase bone loss, have a reduced fracture rate when they received denosumab. So that is the big take-home message, and a medium follow-up of 8 years. But the secondary endpoints included disease-free survival. They had about 20% disease-free survival events and 8% deaths, and what they saw was really interesting. So, the caveat is that 16% of patients were unblinded at the first analysis and half of them got denosumab, so it messed up their results a little bit, but the disease-free survival was significantly better in patients who received denosumab, and the hazard ratio of 0.83 and the hazard ratio does not cross 1. So that's very interesting, and even overall survival, they looked at 2 other endpoints, bone metastasis-free survival, and overall survival. They also trend towards an improvement with a hazard ratio of 0.8 for both of them. And they didn't actually see toxicity. So, patients' brittle bone fractures and osteonecrosis of the jaw (ONJ) are all concerning, but they really just did not see any risks in this patient population. I think there was 1 patient that had what they thought was a brittle bone fracture. Obviously, they watched the mouth very carefully as well. Really dramatic, and I think it's kind of disappointing that we never had any registration approach in this, and also not well-understood why the D-CARE study did not show a benefit, but I think D-CARE was designed differently. This is a better design to focus on our patients and the specific issues, and I think it's intriguing and should be considered as part of our treatment regimen for patients who are at risk for bone loss and have early-stage breast cancer on an aromatase inhibitor. Dr. Allison Zibelli: I've been using DEXA scans and offering denosumab to my patients on AIs that have osteopenia or osteoporosis. Should we be considering it in women with normal bone mass? Dr. Hope Rugo: I think not yet. Unfortunately, this trial was not immediately powered for cancer outcome, although the data are very encouraging. We don't know what the relationship is to bone loss, and providing an environment that's friendlier for cancer cells. So, do you have to have bone loss in order to have the risk that you're reducing with these agents? Certainly, that's what we've seen with zoledronate. So, I think that we don't have sufficient data to use this simply to treat cancer, but I do think that we should be considering this as an agent to give patients who have bone loss, either when you're starting an aromatase inhibitor or during the course of therapy. I think it's well tolerated, and a subcutaneous injection is not difficult. One of the questions that's come up for people is do you get bone loss that increases your risk of fracture after you stop therapy. But clearly from these updated data, these patients were off therapy. They did not have an increase of fractures and the patients treated with denosumab fared much better, I mean the hazard ratio of 0.5. Dr. Allison Zibelli: Let's move on to TROPiCS-02. That's LBA1001. This is a randomized phase 3 study of sacituzumab govitecan versus treatment of physician's choice in patients with hormone receptor-positive, HER2-negative advanced breast cancer. How do you think this study will impact practice? Dr. Hope Rugo: That's a great question. I presented this data, and I think I presented it on a Saturday, and on Sunday we saw the plenary talk of DESTINY-Breast04. These patients enrolled in TROPiCs-02 had a median number of lines of prior chemo 3 with a range of up to 8 actually, compared to a median number of lines as 1 in the DESTINY-Breast04 population. We included all hormone receptor-positive HER2 negative-advanced breast cancer, not centrally confirmed. They included just the HER2 low subset that was centrally confirmed. Everybody in our study had received prior CDK4/6 inhibitors compared to about 70% in DB04. And then 95% of patients in this trial had visceral mets. So, we did really treat a patient population who had very advanced high risk hormone receptor-positive breast cancer. As you know, we saw an improvement and progression-free survival with a hazard ratio of 0.66 meeting the endpoint. We needed a hazard ratio of 0.7, highly statistically significant P value .0003, but the median difference in PFS was only 1.5 months, and overall survival data is not yet mature. So that's brought up the question about how this drug should be used because there was a big fall off in the first 2 months where patients had rapid disease progression with heavily pretreated chemotherapy-resistant disease. We did landmark analyses and there were big separations in PFS at 6, 9, and 12 months, and 12 months, it was 21% patients free of progression and death at 1 year versus 7% for the TPC arm. So, it was a tripling of patients who were free of progression at one year. I think that's clinically relevant. This drug is associated with more neutropenia. That's the primary issue to manage, and probably half of the patients need growth factors at some point. When we looked at other endpoints response to ratio response, etc., we're better with Sacituzumab. So where does this all fit into our treatment paradigm. I think there's the HER2-low patients who will now receive T-DXd up in the, I hope, second line and not in lieu of endocrine therapy, when they're ready for chemo. But there are patients who don't have HER2-low disease and then there are patients who are going to be in the later line setting. So, I do think it still has a place in the treatment department, receptor-positive metastatic breast cancer. The results show that it was better than chemotherapy, physician choice based on our national and international guidelines, and that's better for our patients to have that option. Overall survival data obviously is looked for with great interest and that will help us put this into the right paradigm. And then I also hope that real world data will help us understand how sequential treatment with these different ADCs will benefit our patients. Dr. Allison Zibelli: This is really exciting. Do you think that we're maybe coming toward the end of conventional chemotherapy, especially for women with HER2-positive disease? Dr. Hope Rugo: I wonder if we are. I think we were interested in T-DM1 for HER2-positive disease early on. We've seen some really nice pathologic complete response data as well as adjuvant data in the attempt trial in patients who had stage I disease. Now that we have these second-, third-generation ADCs, T-DXd, I think this could potentially completely replace our chemotherapy. We still have to deal with alopecia. And I will point out ADCs are still chemotherapy. They're just a much more efficient and effective way of delivering treatment, and we need to be very careful to manage the toxicity. Dr. Allison Zibelli: Next, we're going to talk about the main pain trial that's LBA1004, which is a randomized phase 2 trial of fulvestrant or exemestane with or without ribociclib after progression on anti-estrogen therapy plus cyclin-dependent kinase 4/6 inhibition in patients with unresectable or hormone receptor-positive HER2-negative metastatic breast cancer, in other words CDK4/6 after CDK4/6. What are your takeaways here? Dr. Hope Rugo: First, just amazing that an investigator-initiated trial could do this well and be placebo-controlled. So, kudos to the principal investigator (PI) [Dr.] Kevin Kalinsky. This trial is a small phase 2 trial. A reasonable number, 119 patients were randomly assigned and evaluable patients could have received up to 1 line of prior chemotherapy for metastatic disease. If you had received prior exemestane, you received fulvestrant, if you received prior fulvestrant, you received exemestane, and actually if you looked at the number of patients who had received fulvestrant, it was 99 versus only 20 with exemestane. So important to keep in mind. If you looked at the overall population where the primary endpoint was progression-free survival, the hazard ratio is 0.57, just median PFS of 2.8 months in patients receiving endocrine therapy and placebo and 5.3 months for patients receiving endocrine therapy and ribociclib. So was this ribociclib after ribociclib or ribociclib after something else. 86% of patients had received palbociclib as their prior CDK4/6 inhibitor, and only about 10% to 14% had received prior ribociclib. So, there's a predominance of palbociclib followed by ribociclib. The other thing that's important to keep in mind is how sick this patient population was. Very few had received prior chemotherapy in the less than 10% range, visceral metastases in about 60%. So that's helpful. Only 19% or so had received 2 or more endocrine therapies from metastases. So, most people did this as their second line treatment. The PFS, when you looked at fulvestrant or exemestane, looked like the benefit was relatively similar, but you know you got 20 patients in the exemestane arm. The hazard ratios, looking at the subgroup analyses, all looked pretty similar, and the overall response and clinical benefit rate were better with continuing the cyclin dependent kinases (CDK) inhibitor. There was interesting sub-analysis looking at mutations and how that affected things. And they looked at patients who had ESR1 mutations or had wild-type ESR1. 42% had ESR1 mutations at study entry, very similar to what we've seen. In that group of patients, remember it's only 33 where they had this analysis, they saw a lot of other mutations. So p53, PIK3CA, FGFR, CCND1—those patients did not benefit. Only 33 patients. No benefit at all, very short PFS, about 3 months. The patients who had ESR1 wild type seemed to benefit a lot, 45 patients going from about 3 months to a little over 8 months. So, this is all hypothesis-generating data. I wouldn't run out and use this as your standard of care now because it is small data. But when the patient doesn't have other good options, I certainly would consider switching the CDK and going on, add that to the next line endocrine therapy. It's important to switch the endocrine therapy. I think we really need to look at the ongoing phase 3 trials to give us better evidence basis and understand the impact of mutations and prior therapy on who might benefit from continued CDK inhibitors after progression on a CDK inhibitor. Dr. Allison Zibelli: I think this is a really exciting trial. We all have a lot of patients on palbociclib and letrozole who've been on for 4, 5 years, and would like to continue with this kind of treatment because the side effects are really manageable. So, I look forward to seeing what's coming in the future with the phase 3 trials. So, let's talk about Abstract 1015, which I thought is a great idea. It looks at the quality of life with ribociclib plus aromatase inhibitor versus abemaciclib plus AI as first-line treatment of hormone receptor-positive, HER2-negative advanced breast cancer, assessed via matching adjusted indirect comparison. Could you tell us what matching adjusted indirect comparison is and why you chose this for the study? Dr. Hope Rugo: It's an interesting question. How do you compare across trials? So, matching this kind of make analysis, we'll call it a make analysis for the purposes of this discussion, allows you to match patients and weight based on their characteristics that might affect patient reported outcomes. And that actually is a way of trying to do a fair cross-trial comparison. So basically, take the study population, you match the inclusion and exclusion criteria, and then you weigh the different criteria so that you can try and make a better association. It's the best way we know of comparing across trials. You know, a lot of people ask why we didn't have PALOMA-2 in here, and that's because they used a different patient reported outcome tool. So, you have to use the same patient reported outcome tool in order to compare. So that's why we did this analysis, and it sort of came on the heels of a survey that Fatima Cardoso presented at San Antonio in 2021, where patients identified diarrhea as a symptom they really didn't like more than everything else. And you can imagine, I think we all have that experience in practice, the unexpected nature of diarrhea and the fact that it does limit your activities and, therefore, quality of life are important. In this analysis, interestingly but not surprisingly, ribociclib favored abemaciclib in diarrhea, and there can be associated appetite loss, so ribociclib also favored abemaciclib for appetite loss. And I thought the last one was interesting—fatigue—because I wouldn't have assumed that fatigue would be different. And maybe it's associated with diarrhea. They have these funny arm symptoms that were better. We don't really know why that was, and it's hard to assess again. We're really not clear based on the differences between the drugs. So, there are limitations to the analysis, but I think that it helps us really in individual patients try and match patients' underlying symptoms with the best treatment to offer them the best quality of life as they're being treated in the metastatic setting. Dr. Allison Zibelli: I thought this study was great because it really centered the experience of the patient and the wishes of the patient. You don't see that designed into many clinical trials, the way this was. So, I thought that was a great feature of this study. Dr. Hope Rugo: I will say that all of the 3 studies that looked at CDK inhibitors, all those 3 studies included patient-reported outcomes. That's an important new approach that is really being focused on. Dr. Allison Zibelli: Do you consider the CDK4/6 inhibitors equivalent in efficacy, and could you substitute them to try to get the side effect profile that you want? Dr. Hope Rugo: Well, I think that we saw in the early stage setting that there are differences. Now, across the different trials, there are big differences in patient populations and inclusions as we saw in the PALOMA-2 results that were presented at ASCO [Annual Meeting], whether the patients had prior chemotherapy like in PALOMA-3, whether they had a short disease-free interval, the higher risk patients in PALOMA-2. The PALOMA trials were more broadly inclusive than the other 2 studies, the MONALEESA and MONARCH series of trials. So, we do have to be a little bit careful about comparing apples to oranges, but we have the early-stage results of MONARCH E showing a clinically important difference in outcome whereas the PALLAS and Penelope-B trials didn't. So that sort of puts us into a little bit of a question period. Are these all patient populations or are there differences between the agents? The PFS and the metastatic setting, all the hazard ratios line up. So, in truth, although I know the activity against cyclin-independent kinases are different between agents, we don't still really understand the clinical differences in efficacy, but I think we all are practicing using evidence-based medicine. I wouldn't, for example, substitute a different CDK4/6 inhibitor for abemaciclib in the treatment of early-stage breast cancer. We have to just learn how to manage the diarrhea and use prophylaxis and dose reduce early to manage this and make it tolerable for our patients. And in the metastatic setting, I think we need to follow evidence-based guidelines and use the best data available to decide on the right treatment approach and sequencing for our patients. Dr. Allison Zibelli: Thank you, Hope, for coming on the podcast today. This was a really interesting review of one of the most exciting ASCO [Annual Meetings] I've been to. And thanks for sharing your valuable insights with us and helping us make sense of all this really new exciting data. We really appreciate it. Dr. Hope Rugo: Thank you. And thank you so much for inviting me. Dr. Allison Zibelli: And thank you to our listeners for joining us today. You will find the links to all the abstracts discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review, and subscribe wherever you get your podcasts. That really helps other listeners find us. Thank you.   Disclosures: Dr. Allison Zibelli: None disclosed. Dr. Hope Rugo: Honoraria: Puma Biotechnology, Mylan, Samsung Bioepis, Chugai Pharma, Blueprint Medicines Consulting or Advisory Role: Napo Pharmaceuticals Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Genentech, Merck, Odonate Therapeutics, Daiichi Sankyo, Sermonix Pharmaceuticals, AstraZeneca, Gilead Sciences, Ayala Pharmaceuticals, Astellas Pharma, Seattle Genetics, Macrogenics, Boehringer Ingelheim, Polyphor 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.

Mining Stock Daily
Morning Briefing: Meridian Drills News Au-Ag Discovery; Minera Alamos Receives Key Approval for Cerro de Oro

Mining Stock Daily

Play Episode Listen Later Jun 21, 2022 10:21


We have new drill results to report from Meridian Mining, Freegold Ventures and EMX Royalty. Mineral Alamos has received its surface rights agreements for its Cerro De Oro. Arras Minerals has published its mineral resource estimate for Beskauga. FPX Nickel has a new MOA with Binche Keyoh Bu Society. We'd like to thank our sponsors: Integra Resources is advancing the past-producing DeLamar Project in southwestern Idaho. The Company has continued to demonstrate resource growth and conversion through greenfield and brownfield exploration. Integra Resources trades on the TSX-V under ITR and the NYSE American under ITRG. Western Copper and Gold is focused on developing the world-class Casino project in Canada's Yukon Territory. The Casino project consists of an impressive 11 billion pounds of copper and 21 million ounces of gold in an overall resource. Western Copper and Gold trades on the TSX and the NYSE American with WRN. Be sure to follow the company via their website,www.westerncopperandgold.com. Rio-2 is advancing the Fenix Gold Project in Chile, the largest undeveloped gold heap leach project in the Americas. Fenix consists of 5 million ounces in the measured and indicated resource category and 1.4 million ounces in the inferred resource category. With a robust PFS in place, Fenix is set up for fast-tracked construction and production. You can find a list of project and company information on their website, rio2.com. ASCU is a Copper Mining Company with a 100% ownership of The Cactus Mine, located on private land in the Arizona Copper Belt. The Company is committed to supplying LME Grade A Copper Cathodes usable in the Renewable Energy Future, mined in a responsible and sustainable manner. Our goal, beyond our ESG Strategy, is to ensure “Net Zero Carbon Emission” from future operations, minimizing the effect of climate change on the earth and preserving our planet for our children and future generations. https://arizonasonoran.com/

Property and Freedom Podcast
PFP153 | Richard, Taghizadegan, Martland, Gabb, Model: “Discussion—Q&A” (PFS 2016)

Property and Freedom Podcast

Play Episode Listen Later Jun 21, 2022


Property and Freedom Podcast, Episode 153. This panel discussion is from the 2016 meeting of the Property and Freedom Society. Olivier Richard (Switzerland), Rahim Taghizadegan (Austria), Keir Martland (England), Sean Gabb (England), Daniel Model (Liechtenstein; Model Holding), “Discussion—Q&A.” PFS 2016 Playlist.

Financial Sense(R) Newshour
The Courage to Face COVID-19

Financial Sense(R) Newshour

Play Episode Listen Later Jun 20, 2022 29:50


Jun 20 – Jim Puplava welcomes Dr. Peter McCullough to discuss his new book The Courage to Face COVID-19, vaccination, what works against COVID, whether children should be vaccinated, and much more... Subscribe to our premium weekday podcasts: https://www.financialsense.com/subscribe

Financial Sense(R) Newshour
Weekend Edition: Fed Not Done, Draining Liquidity, and Energy Heading Higher

Financial Sense(R) Newshour

Play Episode Listen Later Jun 18, 2022 64:33


Jun 17 – After this week's market wrap-up, Financial Sense Newshour speaks with Bloomberg's Head Equities Strategist Gina Martin Adams who sees the Fed Funds rate rising to 3% by year end before the... Subscribe to our premium weekday podcasts: https://www.financialsense.com/subscribe

ASCO Daily News
Advances in Lung Cancer at ASCO22

ASCO Daily News

Play Episode Listen Later Jun 17, 2022 18:22


Guest host Dr. Vamsi Velcheti, of the NYU Langone Perlmutter Cancer Center, and Dr. Brian Henick, of the Columbia University Herbert Irving Comprehensive Cancer Center, discuss advances in KRAS-mutated lung cancer in the KRYSTAL-1 trial, and the association of ctDNA with overall survival in the NADIM trial, as well as other key advances in lung cancer presented at the 2022 ASCO Annual Meeting.   TRANSCRIPT   Dr. Vamsi Velcheti: Hello, everyone! This is Dr. Vamsi Velcheti, I'm your guest host for the ASCO Daily News podcast, today. I'm an associate professor and medical director for the Thoracic Oncology Program at Perlmutter Cancer Center at NYU Langone Health. My guest today is Dr. Brian Henick, an associate director of the Experimental Therapeutics Program, and assistant professor of Medicine at Columbia University's Herbert Irving Comprehensive Cancer Center. We'll be discussing key abstracts in lung cancer that were featured at the 2022 ASCO Annual Meeting. Our full disclosures are available in the notes and disclosures of all guests on the podcast can be found on the transcripts at asco.org/podcasts. Brian, it's great to speak with you today. Dr. Brain Henick: Thank you so much, Vamsi, and ASCO Daily News for letting me join you to discuss these abstracts. Dr. Vamsi Velcheti: So, let's dive in. So, it's an exciting ASCO Annual Meeting. And I hope you had a great time at the Meeting. So, let's start off with the LBA9009 and KRYSTAL-1 clinical trial. The study showed the activity of adagrasib in patients with KRAS-G12C mutant non-small cell lung cancer and active untreated brain mets. So, what is the key takeaway from this trial? Dr. Brain Henick: Well, Dr. Sabari presented some encouraging data on this important population. As we know, patients with active central nervous system (CNS) metastases represent a population of unmet medical need who are often excluded from clinical trials. So, it's a credit to the investigators for including this cohort. As Dr. Sabari noted, and as Dr. Goldberg emphasized in her discussion of the abstract, the measured CNS penetration of adagrasib compares favorably with other CNS active compounds from other settings. The overall response rate was 35%, with a disease control rate of 80%. But impressively, the median duration of intracranial response and progression-free survival (PFS) wasn't reached. This certainly seems to be a CNS active compound, and we'll need to see how sotorasib stacks up in their comparable cohort. Ideally, we'd have randomized data to prove superiority over the standard of care, but we may be a few steps away from that. Dr. Vamsi Velcheti: So, Brian, in terms of CNS mets, how big of a problem is it in patients with KRAS G12C mutant lung cancers? Dr. Brian Henick: We know that CNS metastases are a big problem for G12C mutant lung cancer. The rates have been quoted as high as up to 42% of patients. And in particular, as you know, Vamsi, a lot of times trials often don't include, specifically, cohorts with active untreated brain metastases. And so, this is a very unique cohort in that sense. Dr. Vamsi Velcheti: I just want to highlight that we really don't know the differential efficacy of sotorasib and adagrasib in the CNS met population because the trials were CodeBreak 100 and other trials and data readouts from sotorasib did not include patients with untreated brain mets. We did, however, [see] CNS progression-free survival data that go in line with sotorasib. So, it's really important to see that data from sotorasib. Dr. Brain Henick: I definitely look forward to seeing that. Dr. Vamsi Velcheti: So, let's talk about Abstract 8501. The primary endpoint that was presented at ASCO [Annual Meeting] was the pathologic complete response to chemotherapy and nivo vs. chemotherapy as a new adjuvant treatment for resectable stage 3, a non-small cell lung cancer. This was the phase 2 NADIM trial. So, what do you think about this study? And what's your key takeaway from the study? Dr. Brain Henick: Dr. Provencio from Spain presented data from this randomized study as you said, of nivo plus carbo taxol compared to carbo taxol as neoadjuvant therapy for potentially resectable stage 3-A and B non-small cell lung cancer. So, I did want to compare this to the randomized data that we have from Checkmate 816, which interestingly allowed for earlier-stage disease as low as 1-B. And they also allowed for more flexibility in the choice of platinum doublet regimens. This study, NADIM 2, employs 2:1 versus 1:1 randomization, which we saw in Checkmate 816. Another important difference was that NADIM 2 required adjuvant nivolumab for 6 months in the study arm, whereas Checkmate 816 didn't include any immunotherapy in the adjuvant setting, but they allowed for a standard of care chemotherapy. In NADIM 2, the control arm didn't include any adjuvant therapy. In keeping with the impressive improvements over historical pathologic complete response rates of about 5%, this chemotherapy-IO regimen yielded a path complete response (CR) rate of 36.8%. It also showed a major pathological response, which again is defined as less than 10% viable tumor of 52.6%, and an overall response rate of 75.4%. So, it looks like there's a benefit that's happening upfront with the immunotherapy and chemotherapy as opposed to this just being an adjuvant phenomenon. This is also in keeping with data that we saw with Checkmate 816, as well as neoadjuvant atezo plus chemotherapy in the phase 2 study that was led by Catherine Shu and colleagues here at Columbia a few years ago. Overall, this is more encouraging data for the neoadjuvant use of immunotherapy. The earlier immunotherapy marches into the treatment course of patients with lung cancer, the greater the cost of toxicity. So, I think an important thing for us to focus on going forward is trying to develop strategies to better identify the patients that are most likely to benefit. Dr. Vamsi Velcheti: So, Brian, I think from a practical standpoint, now that we have approval for neoadjuvant immunotherapy and adjuvant immunotherapy, we have some practical challenges in terms of how we manage our patients. Of course, the new adjuvant is very appealing because it's only 3 cycles of chemoimmunotherapy, but the challenge though, is a majority of the patients don't have a CR, or a significant proportion of the patients have an ongoing response or significant residual disease at the time of surgery. So, the question then would be what do you do after surgery if they're having an ongoing response? Do you think 3 cycles of immunotherapy are inadequate systemic therapy for these patients? Dr. Brian Henick: It's a really important question, Vamsi. I think until the data is mature, we're just kind of limited by the extent of what the data tells us so far, and then we have to kind of do our best as the treating doctor to navigate the patient's situation. So, tools that we'd still have available to us in the adjuvant setting that are approved are things like chemotherapy and radiation, leveraging things like circulating tumor DNA, I think maybe a promising path forward, as well to help guide strategies there, but I think until the data is mature, it has to be highly patient-focused to figure out what seems to be most appropriate there. How are you navigating those situations, Vamsi? Dr. Vamsi Velcheti: Yeah, as you said, it is very challenging. I think we need more data. And of course, the challenge now is like, if you use immunotherapy in the new adjuvant setting, it's very likely you're not going to get insurance authorization for 1 year of adjuvant atezolizumab. So, we really need studies to optimize treatment paradigms here. As you suggested, maybe circulating tumor DNA (ctDNA)-based approaches to look at residual disease, I think, that would be one great way to do it. Let's move on to the next abstract, Brian. I found Abstract 9001 really interesting. It's a U.S. Food and Drug Administration (FDA) pooled analysis that looked at outcomes of first-line immune checkpoint inhibitors, with or without chemotherapy based on the KRAS mutation status and PD-L1 expression. So, what is your take on this abstract and how do you think this is going to impact our practice? Dr. Brian Henick: So, Dr. Nakajima and colleagues explored the observation from individual trials that patients with KRAS-mutant lung cancer seem to have better responses than wild type with immunotherapy (IO) alone. But the favorability of these responses seems to be abrogated with chemotherapy-IO. We know that KRAS accounts for 25% of oncogene-driven non-small cell lung cancer predominantly at amino acid 12. And with the emergence of direct inhibitors of G12C, understanding the clinical features of these tumors may be critical to inform optimal integration of this new class of drugs and also to make sure that we've optimized treatment algorithms for KRAS patients in general. So, this study's authors at the FDA pulled data from 12 registrational clinical trials that were investigating first-line checkpoint inhibitor-containing regimens and they found no significant difference between KRAS wild type and mutant for overall survival regardless of the regimen used. The best outcomes were seen with chemoimmunotherapy regardless of KRAS status. This retrospective analysis does suggest that the notion of there being lesser benefit from chemoimmunotherapy from Dr. Gadgeel's study might not hold up in the overall population, but I think it raises important questions, like, are all KRAS mutations alike? The absence of KRAS mutation status for a majority of patients included in these studies limits the interpretation of the data. And also, the absence of commutation status makes it a little harder to interpret. And other important questions remain such as how G12C inhibitors will factor in? What were your thoughts, Vamsi? Dr. Vamsi Velcheti: No, I completely agree with you, Brian. I think we need more data and we know that commutation status is a very important aspect in terms of KRAS-directed therapies. And of course, with a lot of promising data from these KRAS inhibitors, there's an interest in moving these drugs into the front-line therapy for patients with KRAS mutations. But I think it's going to be quite challenging to incorporate them into the front-line therapies and we clearly will need better characterization of these patients with KRAS mutant [lung cancer] to further personalize treatment in the frontline setting for these patients. So, let's move on to the next abstract. This is the lung map study, Abstract 9004. This is a study sponsored by the National Cancer Institute (NCI), the lung map study, looking at overall survival from a phase 2 randomized study of ramucirumab and pembrolizumab, what's the standard of care in patients with advanced non—small cell lung cancer previously treated with immunotherapy. So, what were your key takeaway points here from this study? Dr. Brian Henick: So first of all, it's very exciting to see data from this very ambitious long map sub-study yield a positive result. Whereas many of the arms of this study were biomarker-guided, Dr. Reckamp presented the results from pembro plus ramucirumab as compared to the standard of care in unmarked patients with non-small cell lung cancer who had progressed after prior treatment with chemotherapy and immunotherapy. The data seems to suggest that pembro plus ramucirumab may be better tolerated than the standard of care chemo-containing regimens, as the experimental regimen had fewer serious adverse events. Pembro plus ramucirumab had a median overall survival of 14.6 months as compared to 11.6 months in the control arm and this was statistically significant. The PFS difference wasn't significant, but there was a late divergence in the curves. Dr. Bestvina nicely summarized some of the study's limitations such as the mixture of control regimens used, and there were really interesting signals that were found on subgroup analysis, such as benefit in those with mixed histology tumors, STK11 mutant tumors, and those who received chemotherapy prior to immunotherapy. The subgroups deserve further attention in the future. For now, this regimen may be an appealing option as an alternative to chemotherapy for the right patients. What do you think? Dr. Vamsi Velcheti: Yeah, I agree, Brian. I think it's a really promising combination. We've always seen some synergy with VEGF inhibitors and immunotherapy in multiple studies and multiple tumor types. So, we really need to develop better ways to select patients for VEGF combination-based approaches in lung cancer. So, let's move on to another interesting study. This is Abstract 9000. This explores the outcomes of anti-PD-L1 therapy with or without chemotherapy for first-line, metastatic non-small cell lung cancer with a PD-L1 score of greater than 50%. So, this is an FDA pooled analysis. So, what were your key takeaways from this abstract? Dr. Brain Henick: I thought this question was really well suited for a large pooled retrospective analysis and our colleagues at the FDA didn't let us down here. The question really was what's the optimal approach for patients with non-small cell lung cancer with greater than 50% PD-L1 in view of the absence of direct comparisons between these arms in prospective studies? I thought one of the most striking findings from Dr. Akinboro's presentation was the dismally low rate of underrepresented minority patients that were included in these registration trials. As far as the findings for the patients who were studied, although the Kaplan-Meier curves for overall survival showed early separation, the difference wasn't statistically significant. Subgroup analysis revealed a trend towards better outcomes for immunotherapy alone among patients who are [age] 75 and above, suggesting that this may need to be parsed out as a unique population in subsequent studies. But in all, our equipoise as a field on whether to include chemoimmunotherapy-based first-line regimens should persist and should be guided, in my opinion, largely by clinical considerations. Can the patient tolerate chemotherapy? Do you need a rapid response? Are there other things that you thought in hearing all this, Vamsi? Dr. Vamsi Velcheti: Yeah, absolutely. I think I am still struggling with the decision of whether to add chemotherapy for patients with greater than 50%. To a large extent, it's actually a clinical decision. In some patients who have a large disease burden, I tend to kind of opt for adding chemotherapy to immunotherapy in the front-line setting. But of course, we need more data here. And this is actually a very helpful piece of information from the FDA. And as you pointed out briefly, Brian, I think the fact that there are very few underrepresented patients in the pooled analysis, I think kind of speaks to the need for addressing increased diversity in clinical trial accruals. I think this is a great segue to also talk about Abstract 9012, talking about disparities in access to immunotherapy globally. This is a study from India looking at 15,000 patients who were checkpoint inhibitor eligible and who have very low rates of uptake of immunotherapy. This is something that reflects the global team of the ASCO Annual Meeting talking about disparities and improving access to treatments in underserved minority populations here in the United States, and also globally, in the developing world, the disparities in terms of access to care are humongous. So, what are your thoughts, Brian? And also, if you could highlight some of the work that you're doing at Columbia about disparities, I think that would be great. Dr. Brain Henick: Absolutely! I think access to medications is a really humbling topic for those of us who are involved in developmental therapeutics, particularly with the transformational impact we've seen with the advent of immunotherapy over the last decade-plus. Dr. Ravikrishna's presentation is therefore extremely important. He described very low rates of uptake of immunotherapy by indication. And perhaps most strikingly, the discrepancy in uptake by patients' ability to pay for therapy with the vast majority of immunotherapy received by those who are private is very concerning. Even if the definition of restricted access was permissive, for example, I didn't see mention of the cancer stage as an eligibility factor, the fact that this represents a single referral center's data doesn't bode well for uptake elsewhere. So, I think we need to continue to work as a field on prioritizing strategies to help overcome these gaps, but good quality data such as this study is an important first step. And to that point, Vamsi, I'm very excited to be working with you in collaboration on an observational study for patients with lung cancer from underserved minority populations with lung cancer in New York City so that we can better characterize access to care, efficacy, and toxicity in this population. Dr. Vamsi Velcheti: Thank you, Brian. I'd really like to thank you for sharing your valuable insights with us today on the ASCO Daily News Podcast. We really appreciate it. Brian, thank you so much for joining us. Dr. Brain Henick: My pleasure. Thanks for having me. Dr. Vamsi Velcheti: And thank you to all our listeners for joining in today. You will find links to all the abstracts discussed today in the transcript of this episode. Finally, if you value the insights that you hear on the ASCO Daily News Podcast, please take a moment to rate, review and subscribe wherever you get your podcasts. Thank you so much.     Disclosures: Dr. Vamsi Velcheti: Honoraria: Honoraria Consulting or Advisory Role: Bristol-Myers Squibb, Merck, Foundation Medicine, AstraZeneca/MedImmune, Novartis, Lilly, EMD Serono, GSK, Amgen Research Funding (Inst.): Genentech, Trovagene, Eisai, OncoPlex Diagnostics, Alkermes, NantOmics, Genoptix, Altor BioScience, Merck, Bristol-Myers Squibb, Atreca, Heat Biologics, Leap Therapeutics, RSIP Vision, GlaxoSmithKline Dr. Brain Henick: None disclosed. Disclaimer: The purpose of this podcast is to educate and inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. 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.

Mining Stock Daily
The Bond Market is Important to Watch and Inflationary Pressures will Persist

Mining Stock Daily

Play Episode Listen Later Jun 17, 2022 52:27


Two conversaiton coming off PDAC. First, Dave Lotan joins us to discuss the bond market and some of the macro indicators he's keen to follow closely in this volatile market. Last, Wheaton Precious Metals CEO, Randy Smallwood, provides his take on inflation, the capital needed to fund and build new projects, and why inflation will continue to be a thorn in the side for economies. We'd like to thank our sponsors: Integra Resources is advancing the past-producing DeLamar Project in southwestern Idaho. The Company has continued to demonstrate resource growth and conversion through greenfield and brownfield exploration. Integra Resources trades on the TSX-V under ITR and the NYSE American under ITRG. Western Copper and Gold is focused on developing the world-class Casino project in Canada's Yukon Territory. The Casino project consists of an impressive 11 billion pounds of copper and 21 million ounces of gold in an overall resource. Western Copper and Gold trades on the TSX and the NYSE American with WRN. Be sure to follow the company via their website,www.westerncopperandgold.com. Rio-2 is advancing the Fenix Gold Project in Chile, the largest undeveloped gold heap leach project in the Americas. Fenix consists of 5 million ounces in the measured and indicated resource category and 1.4 million ounces in the inferred resource category. With a robust PFS in place, Fenix is set up for fast-tracked construction and production. You can find a list of project and company information on their website, rio2.com. ASCU is a Copper Mining Company with a 100% ownership of The Cactus Mine, located on private land in the Arizona Copper Belt. The Company is committed to supplying LME Grade A Copper Cathodes usable in the Renewable Energy Future, mined in a responsible and sustainable manner. Our goal, beyond our ESG Strategy, is to ensure “Net Zero Carbon Emission” from future operations, minimizing the effect of climate change on the earth and preserving our planet for our children and future generations. https://arizonasonoran.com/

Property and Freedom Podcast
PFP151 | Sean Gabb, “Margaret Thatcher—Hero or Villain?” (PFS 2016)

Property and Freedom Podcast

Play Episode Listen Later Jun 17, 2022


Property and Freedom Podcast, Episode 151. This talk is from the 2016 meeting of the Property and Freedom Society. Sean Gabb (England), “Margaret Thatcher—Hero or Villain?” PFS 2016 Playlist.

Property and Freedom Podcast
PFP150 | Keir Martland, “How Glorious was the ‘Glorious Revolution'?” (PFS 2016)

Property and Freedom Podcast

Play Episode Listen Later Jun 16, 2022


Property and Freedom Podcast, Episode 150. This talk is from the 2016 meeting of the Property and Freedom Society. Keir Martland (England), “How Glorious was the ‘Glorious Revolution'?” PFS 2016 Playlist.

Property and Freedom Podcast
PFP149 | Hans-Hermann Hoppe, Introductions, Day 1, Afternoon Sessions (PFS 2016)

Property and Freedom Podcast

Play Episode Listen Later Jun 16, 2022


Property and Freedom Podcast, Episode 149. This is Professor Hans-Hermann Hoppe‘s (Germany/Turkey) introduction before the afternoon talks on Day 1 of the 2016 meeting of the Property and Freedom Society. PFS 2016 Playlist.

Property and Freedom Podcast
PFP148 | Rahim Taghizadegan, On the Rise and Fall of the University (PFS 2016)

Property and Freedom Podcast

Play Episode Listen Later Jun 15, 2022


Property and Freedom Podcast, Episode 147. This talk is from the 2016 meeting of the Property and Freedom Society. Rahim Taghizadegan (Austria), On the Rise and Fall of the University. PFS 2016 Playlist.

Financial Sense(R) Newshour
Jim Rickards on Economic Warfare, Russia Win, and US Recession

Financial Sense(R) Newshour

Play Episode Listen Later Jun 14, 2022 44:40


Jun 14 – Financial Sense Newshour speaks with well-known strategist and author Jim Rickards who says the biggest economic impacts of the Russia-Ukraine war have yet to hit the globe and explains when... Subscribe to our premium weekday podcasts: https://www.financialsense.com/subscribe

Property and Freedom Podcast
PFP147 | Olivier Richard, On Free and Compulsory Education (PFS 2016)

Property and Freedom Podcast

Play Episode Listen Later Jun 14, 2022


Property and Freedom Podcast, Episode 147. This talk is from the 2016 meeting of the Property and Freedom Society. Olivier Richard (Switzerland), On Free and Compulsory Education. PFS 2016 Playlist.

Property and Freedom Podcast
PFP146 | Hans-Hermann Hoppe, Introductions, Day 1, Morning Sessions (PFS 2016)

Property and Freedom Podcast

Play Episode Listen Later Jun 14, 2022


Property and Freedom Podcast, Episode 146. This is Professor Hans-Hermann Hoppe‘s (Germany/Turkey) introduction before the morning sessions on Day 1 of the 2016 meeting of the Property and Freedom Society. PFS 2016 Playlist.

Financial Sense(R) Newshour
Using the 1970s Playbook for Retirement Planning this Decade

Financial Sense(R) Newshour

Play Episode Listen Later Jun 14, 2022 26:51


Jun 13 – Investing in the markets and planning for retirement is going to be more difficult in the years ahead but there's a good way to think about how to navigate this period. Today, we discuss the... Subscribe to our premium weekday podcasts: https://www.financialsense.com/subscribe

Property and Freedom Podcast
PFP145 | Hoppe, Dürr, Kinsella, van Dun, Daniels, Discussion, Q&A (PFS 2015)

Property and Freedom Podcast

Play Episode Listen Later Jun 13, 2022 56:29


Property and Freedom Podcast, Episode 145. This panel discussion is from the 2015 meeting of the Property and Freedom Society. Hans-Hermann Hoppe (Germany/Turkey), David Dürr (Switzerland), Stephan Kinsella (USA), Frank Van Dun (Belgium), Anthony Daniels (Theodore Dalrymple) (England), “Discussion, Q&A.” PFS 2015 Playlist.