Podcasts about Aadi

Amrita and Andrew never considered dating, but they did choose to build a life and a family together. They met as coworkers and remained friends until one night, over a casual beer, Andrew floated the idea of having kids together. Amrita surprised even herself by saying yes. In this episode, these ‘platonic soulmates' talk about what it's like to live together, co-parent their son Aadi, and run a business, all while keeping their relationship platonic.You can learn more about Amrita and Andrew by watching their viral video and subscribing to their free Substack Emergency Contacts, about the power of intimate friendship, and reflections on partnership, family, love, and parenting. Everyone has a story worth sharing.

Unknown Gunmen Destroy Pakistan's Weapons in Karachi | Trump v Iran, Chabahar, Afg | Aadi Achint

Is Modi Losing the Game Against Trump or Winning it? | Iran | Pax Americana | China | Aadi Achint

Dr. Hope Rugo and Dr. Vivek Subbiah discuss innovative trial designs to enable robust studies for smaller patient populations, as well as the promise of precision medicine, novel therapeutic approaches, and global partnerships to advance rare cancer research and improve patient outcomes. TRANSCRIPT  Dr. Hope Rugo: Hello and welcome to By the Book, a podcast series from ASCO that features engaging conversations between editors and authors of the ASCO Educational Book. I am your host, Dr. Hope Rugo. I am the director of the Women's Cancers Program and division chief of breast medical oncology at the City of Hope Cancer Center [in Los Angeles]. The field of rare cancer research is rapidly transforming thanks to progress in clinical trials and treatment strategies, as well as improvements in precision medicine and next-generation sequencing that enable biomarker identification. According to the National Cancer Institute, rare cancers occur in fewer than 150 cases per million each year, but collectively, they represent a significant portion of all cancer diagnoses. And we struggle with the appropriate treatment for these rare cancers in clinical practice. Today, I am delighted to be joined by Dr. Vivek Subbiah, a medical oncologist and the chief of early-phase drug development at the Sarah Cannon Research Institute in Nashville, Tennessee. Dr. Subbiah is the lead author of a paper in the ASCO Educational Book titled "Designing Clinical Trials for Patients with Rare Cancers: Connecting the Zebras," a great title for this topic. He will be telling us about innovative trial designs to enable robust studies for small patient populations, the promise of precision medicine, and novel therapeutic approaches to improve outcomes, and how we can leverage AI now to enroll more patients with rare cancers in clinical trials. Our full disclosures are available in the transcript of this episode.  Dr. Subbiah, it is great to have you on the podcast today. Thanks so much for being here. Dr. Vivek Subbiah: Thank you so much, Dr. Rugo, and it is an honor and pleasure being here. And thank you for doing this podcast for rare cancers. Dr. Hope Rugo: Absolutely. We are excited to talk to you. And congratulations on this fantastic paper. It is such a great resource for our community to better understand what is new in the field of rare cancer research. Of course, rare cancers are complex and multifaceted diseases. And this is a huge challenge for clinical oncologists. You know, our clinics, of course, cannot be designed as we are being very uni-cancer focused to just be for one cancer that is very rare. So, oncologists have to be a jack of all trades in this area. Your paper notes that there are approximately 200 distinct types of rare and ultra-rare cancers. And, by definition, all pediatric cancers are rare cancers. Of course, clinical trials are essential for developing new treatment strategies and improving patient outcomes, and in your paper, you highlight some unique challenges in conducting trials in this rare cancer space. Can you tell us about the challenges and how really innovative trial designs, I think a key issue, are being tailored to the specific needs of patients with rare cancer and, importantly, for these trials? Dr. Vivek Subbiah: Rare cancers present a perfect storm of challenges. First, the patient populations are very small, which makes it really hard to recruit enough participants for traditional type trials. Second, these patients are often geographically dispersed across multiple cities, across multiple states, across multiple countries, across multiple zip codes. So, logistics become complicated. Third, there is often limited awareness among clinicians, which delays referrals and diagnosis. Add to that regulatory hurdles, funding constraints, and you can see why rare cancer trials are so tough to execute. To overcome these barriers, we are seeing some really creative novel trial designs. And there are four different types of trial designs that are helping with enrolling patients with rare cancers. The first one is the basket trial. So let us talk about what basket studies are. Basket studies group patients based on shared genetic biomarkers or shared genetic mutations rather than tumor type. So instead of running separate 20 to 30 to 40 trials, you can study one therapy across multiple cancers. The second type of trial is the umbrella trial. The umbrella trials flip that concept of basket studies. They focus on one cancer type but test multiple targeted therapies within it. The third category of innovative trials are the platform studies. Platform trials are another exciting innovation. They allow new treatment arms to be added or removed as the data matures and as the data evolves, making trials more adaptive and efficient. The final category are decentralized tools in traditional trials, which are helping patients participate closer to where they are so that they can sleep in their own bed, which is, I think, a game changer for accessibility.  These designs maximize efficiency and feasibility for rare cancer research and rare cancer clinical trials. Dr. Hope Rugo: I love the idea of the platform trials that are decentralized. And I know that there is a trial being worked on with ARPA-H (Advanced Research Projects Agency for Health) funding in triple-negative breast cancer as well as in lung cancer, I think, and others with this idea of a platform trial. But it is challenged, I think, by precision medicine and next-generation sequencing where some patients do not have targetable markers, or there isn't a drug to target the marker. I think those are almost the same thing. We have really seen that these precision medicine ideas and NGS have moved the needle in helping to identify genetic alterations. This helps us to be more personalized. It actually helps with platform studies to customize trial enrollment. And we hope that this will result in better outcomes. It also allows us, I think, to study drugs even in the early stage setting more effectively. How can these advances be best applied to the future of rare cancers, as well as the challenges of not finding a marker or not having a drug? Dr. Vivek Subbiah: Thank you so much for that question. I think precision medicine and next-gen sequencing, or NGS, are truly the backbone of modern precision oncology. They have transformed how we think about cancer treatment. Instead of treating based on where the tumor originated or where the tumor started, we now look at the genetic blueprint of cancer. The NGS or next-gen sequencing allows us to sequence millions of DNA fragments quickly. Twenty, 30 years ago, they said we cannot sequence a human genome. Then it took almost a decade to sequence the first human genome. Right now, we have academic centers and commercial sequencing companies that are really democratizing NGS across all sites, not just in academic centers, across all the community sites, so that NGS is now accessible. This means that we can identify these actionable alterations like picking needles in haystacks, like NTRK fusions, RET fusions, or BRAF V600E alterations, high tumor mutational burden. This might occur across not one tumor type, across several different tumor types. So for rare cancers, this is critical because some of these mutations often define the best treatment option. Here is why this matters. Personalized therapy, right? Instead of a one-size-fits-all approach, we can tailor treatment to the patient's unique molecular profile. For trial enrollment, this can definitely help because patients can join biomarker-driven trials even if their cancer type is rare or ultra-rare. NGS technology has also helped us in designing rational studies. Many times monotherapy does not work in these cancers. So we are thinking about rational combination strategies. So NGS technology is helping us. Looking ahead, I see NGS becoming routine in clinical practice, not just at major niche academic centers, but everywhere. We will see more tumor-agnostic approvals, more molecular tumor boards guiding treatment decisions in real time. And I think we are seeing an expanded biomarker setup. Previously, we used to have only a few drugs and a handful of mutations. Now with homologous recombination defects, BRCA1/2 mutation, and expanding the HRD and also immunohistochemistry, we are expanding the biomarker portfolio. So again, I personally believe that the future is precision. What I mean by precision is delivering the right drug to the right patient at the right time. And for rare cancers, this isn't just progress. It is survival. And it is maybe the only way that they can have access to these cutting-edge precision medicines. Dr. Hope Rugo: That is so important. You mentioned an important area we will get to in a moment, the tumor-agnostic therapies. But as part of talking about that, do you think that the trials should also include just standard therapies? You know, who do you give an ADC to and when with these rare cancers? Because some of them do not have biomarkers to target and it is so disappointing for patients and providers where you are trying to screen a patient for a trial or a platform trial where you have one arm with this mutation, one arm with that, and they do not qualify because they only have a p53 loss, you know? They just do not have the marker that helps them. But we see this in breast cancer all the time. And it is tough because we don't have good information on the sequencing. So I wonder, you know, just because for some of these rare cancers it is not even clear what to use when with standard treatments. And then that kind of gets into this idea of the tumor-agnostic therapies that you mentioned. There are a lot of new treatments that are being evaluated. We have seen approval of some treatments in the last few years that are tumor-agnostic and based on a biomarker. Is that the best approach as we go forward for rare cancers? And what new treatment options are most exciting to you right now? Dr. Vivek Subbiah: Tumor-agnostic therapies, really close to my heart, are real breakthrough therapies and represent a major paradigm shift in oncology. Traditionally, for the broad listeners here, we are used to thinking about designing clinical trials and therapy like where the cancer originated, breast cancer, kidney cancer, prostate cancer, lung cancer. A tumor-agnostic therapy flips that model. Instead of focusing on the organ, they target the specific genetic alteration or biomarker that drives cancer growth regardless of where the tumor started, regardless of the location of the tumor, regardless of the zip code of the tumor. So why is this so important for rare cancers? Because many rare cancers share molecular features with more common cancers. For instance, NTRK fusion might occur in pediatric sarcoma, a salivary gland tumor, or a thyroid cancer. Historically, each of these would require separate trials, which is nearly impossible, unfeasible to conduct in these ultra-rare cancers like salivary gland cancer or pediatric sarcomas. Tumor-agnostic therapies allow us to treat all those cancers with the same targeted drug if they share that biomarker. Again, we are in 2025. The first tissue-agnostic approval, the historic precedent, was in fact an immunotherapy. Pembrolizumab was approved in 2017, May 2017, as the first immunotherapy to be approved in a tumor-agnostic way for a genomic biomarker, for MSI-High and dMMR cancers. Then came the NTRK inhibitors. So today we have not one, not two, but three different NTRK inhibitors: larotrectinib, entrectinib, and repotrectinib, which show response rates of nearly more than 60 to 75% across a handful of dozens and dozens of cancer types. Then, of course, we have RET inhibitors like selpercatinib, which is approved tissue-agnostic, and pralsetinib, which also shows tissue-agnostic activity across multiple cancers. And more recently, combination therapy with a BRAF and MEK combination, dabrafenib and trametinib, received tumor-agnostic approval for all BRAF V600E tumors with the exception of colorectal cancer. And even recently, you mentioned about antibody drug conjugates. Again, I think we live in an era of antibody drug conjugates. And Enhertu, trastuzumab deruxtecan, which was used first in breast cancer, now it is approved in a histology-agnostic manner for all HER2-positive tumors defined by immunohistochemistry 3+. So again, beyond NGS, now immunohistochemistry for HER2 is also becoming a biomarker. So again, for the broad listeners here, in addition to comprehensive NGS that may allow patients to find treatment options for these rare cancers for NTRK, RET, and BRAF, immunohistochemistry for HER2 positivity is also emerging as a biomarker given that we have a new FDA approval for this. So I would say personally that these therapies are game changers because they open doors for patients who previously had no options. Instead of waiting for years for a trial in their specific cancer type, they can access a treatment based on their molecular profile. I think it is precision medicine at its finest and best. Looking ahead, the third question you asked me is what is exciting going on? I think we will see more of these approvals. My hope is that today, I think we have nine to ten approvals. My hope is that within the next 25 to 50 years, we will have at least 50 to 100 drugs approved in this space based on a biomarker, not based on a location of the tumor type. Drug targeting rare alterations like FGFR2 fusions, FGFR amplifications, ALK fusions, and even complex signatures like high tumor mutational burden. I think we will be seeing hopefully more and more drugs approved. And as sequencing becomes routine, we will identify more patients for these therapies. I think for rare cancers, this is not just innovative approach. This is essential for them to access these novel precision medicines. Dr. Hope Rugo: Yeah, that is such a good point. I do think it is critical. Interestingly in breast cancer, it hasn't been, you know, there is always like two patients in these tumor-agnostic trials, or if that. You know, I think I have seen one NTRK fusion ever. I think that highlights the importance for rare cancers. And you know, I am hoping that that will translate into some new directions for some of our rarer and impossible-to-treat subtypes of breast cancer. It is this kind of research that is really going to make a difference. But what about those people who do not have biomarkers? What if you do not fit into that? Do you think there is a possibility of trying to do treatments for rare cancers in some prospective way that would help with that? You know, it is really a huge challenge. Dr. Vivek Subbiah: Absolutely. I think, you know, you're right, usually many of these rare cancers are driven by specific biomarkers. And again, some of the pediatric salivary gland tumors or pediatric sarcomas like fibrosarcomas, they are pathognomonic with NTRK fusions. And again, given that we have a tumor-agnostic approval, now these patients have access to these therapies. And I do not think that we would have had a trial just for pediatric fibrosarcomas with NTRK fusions. So that is one way. Another way is SWOG, right? The SWOG DART [1609] had this combination dual checkpoint, it was called the DART study dual combination chemotherapy with ipi/nivo. Now here the rare cancer subtype itself becomes a biomarker and they showed activity across multiple rare cancer subtypes. They didn't require a biomarker. As long as it was a rare or ultra-rare cancer, these patients were enrolled into the SWOG DART trial and multiple arms have read out. Angiosarcoma, Kaposi sarcoma, even gestational trophoblastic disease. Again, they have shown responses in these ultra-rare, rare cancers. Sometimes they might be seeing one or two cases a whole year. And I think this SWOG effort, this cooperative group effort, really highlighted the need for such studies without biomarkers as well. Dr. Hope Rugo: That is such a fantastic example of how to try and treat patients in a collaborative way. And in the paper, you also emphasize the need for collaborative research efforts, you know, uniting resource expertise across different ways of doing research. So cooperative groups, advocacy organizations that can really help advance rare cancer research, improve access to new therapies, and I think importantly influence policy changes. I think this already happened with the agnostic approvals. Could you tell us more about that? How can we move forward with this most effectively? Dr. Vivek Subbiah: Personally, I believe that collaboration is absolutely critical and essential for rare cancer research. No single institution, no single individual, or no single state or entity can tackle these challenges alone. The patient populations are small and dispersed. So pooling resources is the only way to run these meaningful trials. Again, it is not like singing, it is like putting a huge, huge, I would say, an opera piece together. It is not a solo, vocal therapy, but rather putting a huge opera piece like Turandot. You know, you mentioned cooperative groups. Cooperative groups, as I mentioned earlier, the SWOG DART program, the ASCO [TAPUR study]. ASCO is doing a phenomenal work of the TAPUR study. Again, this ASCO TAPUR program has enrolled so many patients with rare cancers who otherwise would not have treatment options. NCI-MATCH, the global effort, right? NCI-MATCH and the ComboMATCH are great examples. They bring together hundreds of sites, thousands of clinicians to run large-scale trials that would be impossible for any individual center or institution. These trials have already changed practice. For instance, the DART demonstrated the power of immunotherapy in rare cancers and influenced NCCN guidelines. One of the arms of the NCI-MATCH study from the BRAF V600E arm contributed towards the BRAF V600E tissue-agnostic approval. So, the BRAF V600E tissue-agnostic approval was by a pooled analysis of several studies. The ROAR study, the Rare Oncology Agnostic Research study, the NCI-MATCH dataset of tumor-agnostic cohort, and another pediatric trial, and also evidence from literature and evidence of case reports. And all this pooled analysis contributed to the tissue-agnostic approval of BRAF V600E across multiple rare cancers. There are several patient advocacy organizations which are the real unsung heroes here. Groups like, for instance, we mentioned in the paper, Target Cancer Foundation, don't just raise awareness for rare cancer research, they actively connect patients to trials providing financial, emotional support, and even run their own studies like the TRACK trial. They also influence policy to make access easier. On a global scale, initiatives like DRUP in the Netherlands, the ROME study in Italy, the PCM4EU in Europe are expanding precision medicine across these borders. These collaborations accelerate research, improve trial enrollment, and ensure patients everywhere can have access to these cutting-edge therapies. Again, it is truly a team effort, right? It is a multi-stakeholder approach. Researchers, clinicians, investigators, industry, regulators, academia, patients, patient advocates, and their caregivers all working together. And it takes a village. Dr. Hope Rugo: Absolutely. I mean, what a nice response to that. And I think really exciting and it is great to see your passion about this as well. But it helps all of us, I think, getting discouraged in treating these cancers to understand what is happening moving forward. And I think it is also a fabulous opportunity for our junior colleagues as they rise up in academics to be involved in these international collaborative efforts which are further expanding. One of the things that comes up for clinical trials for patients, and I think it is highlighted with rare cancers because, as you mentioned, people are all over the place, you know, they are so rare. They are all far away. Our patients are always saying to us, "Should I go here for a phase 1 trial?" Can you talk a little bit about how we can overcome these financial and geographic burdens for the patients? You talked about having trials locally, but it is a big financial and just social burden for patients. Dr. Vivek Subbiah: Great point. Financial cost is a major barrier in rare cancer clinical trials. It is a major barrier not just in rare cancer clinical trials, but in clinical trials in general. The economics of rare cancer research are one of the toughest challenges we face. Developing a new drug is already expensive, often billions of dollars. On an average, it takes 2 billion dollars or 2.8 billion dollars according to some data from drug discovery to approval. For rare cancers, the market is tiny, which means the pharmaceutical companies have really little financial incentive to invest. That is why initiatives like the Orphan Drug Act were created to provide tax credits, grants, and market exclusivity to encourage development for rare diseases. Clinical trials themselves are expensive because the small patient populations mean longer recruitment times and higher per-patient costs. Geographic dispersion, as you mentioned, for the patients adds travel, coordination. That is why we need to think out of the box about decentralized trial infrastructure so that we can mitigate some of these expenses. Complex trial designs like basket or platform trials sometimes require sophisticated data systems and regulatory oversight. That is a challenge. And I think some of the pragmatic studies like ASCO TAPUR have overcome those challenges. Advanced technologies like next-gen sequencing and molecular profiling also add significant upfront cost to this. Funding is also limited because rare cancers receive less attention compared to common cancers. Public funding and cooperative group trials help a lot, but I think they cannot cover everything. Patient advocacy organizations sometimes step in to bridge these gaps, but sustainable financing remains a huge challenge. So, the bottom line is without financial incentives and collaborating funding models, many promising therapies for rare cancers would never make it to patients. That is why we need system-wide policy changes, global partnerships, and innovative, effective, seamless trial designs which are so critical so that they can help reduce the cost and make research feasible so that we can deliver the right drug to the right patient at the right time. Dr. Hope Rugo: There is a lot of excitement about the future integration of AI in screening. Just at the San Antonio Breast Cancer meetings, we have a number of different presentations about AI to find markers, even like HER2, and using AI where you would screen and then match patients to clinical trials. Do you have any guidance for the rare cancer community on how to leverage this technology in order to optimize patient enrollment and, I think, identification of the best treatment matches? Dr. Vivek Subbiah: I think artificial intelligence, AI, is a game-changer in the making. Right now, clinical trial is clunky. Matching patients to trial is often manual, time consuming, laborious. You need a lot of personnel to do that. AI can automate this process by analyzing genomic data, medical records, and trial eligibility criteria to find the best matches quickly, accurately, and effectively. For the community, the key is to invest in data standardization and interoperability because AI needs clean, structured data to work effectively. Dr. Hope Rugo: Thank you so much, Dr. Subbiah, for sharing these fantastic insights with us on the podcast today and for your excellent article. Dr. Vivek Subbiah: Thank you so much. Dr. Hope Rugo: We thank you, our listeners, for joining us today. You will find a link to Dr. Subbiah's Educational Book article in the transcript of this episode. And please join us again next month on By the Book for more insightful views on key issues and innovations that are shaping modern oncology.  Thank you. Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers:        Dr. Hope Rugo   @hoperugo   Dr. Vivek Subbiah @VivekSubbiah Follow ASCO on social media:        ASCO on X  ASCO on Bluesky       ASCO on Facebook        ASCO on LinkedIn        Disclosures:       Dr. Hope Rugo:    Honoraria: Mylan/Viatris, Chugai Pharma   Consulting/Advisory Role: Napo Pharmaceuticals, Sanofi, Bristol Myer   Research Funding (Inst.): OBI Pharma, Pfizer, Novartis, Lilly, Merck, Daiichi Sankyo, AstraZeneca, Gilead Sciences, Hoffman La-Roche AG/Genentech, In., Stemline Therapeutics, Ambryx   Dr. Vivek Subbiah: Consulting/Advisory Role: Loxo/Lilly, Illumina, AADI, Foundation Medicine, Relay Therapeutics, Pfizer, Roche, Bayer, Incyte, Novartis, Pheon Therapeutics, Abbvie Research Funding (Inst.): Novartis, GlaxoSmithKline, NanoCarrier, Northwest Biotherapeutics, Genentech/Roche, Berg Pharma, Bayer, Incyte, Fujifilm, PharmaMar, D3 Oncology Solutions, Pfizer, Amgen, Abbvie, Mutlivir, Blueprint Medicines, Loxo, Vegenics, Takeda, Alfasigma, Agensys, Idera, Boston Biomedical, Inhibrx, Exelixis, Amgen, Turningpoint Therapeutics, Relay Therapeutics Other Relationship: Medscape, Clinical Care Options

Decoding Modi's Game for Bangladesh & Pakistan | ISI Plans | Pentagon | Aadi Achint LIVE

Aadi Saikumar enters the Permit Room and talks about his mindset right now, the movies he liked recently, Saikumar wanting him to be a cricketer, growing up in Chennai, being a fan of Chiranjeevi, playing cricket, Prema Kavali, Lovely, OTT, disappointments, hits, being a father, Shambala and much more!Chapters:00:00 - Mindset right now4:47 - Movies he liked recently8:46 - Did Saikumar want him to be an actor?15:05 - Growing up in Chennai21:25 - Big fan of Chiranjeevi24:07 - Cricket during inter34:32 - Learning dance39:24 - Dubbing is hard44:20 - Prema Kavali & Lovely50:54 - Comedy timing55:15 - Sukumarudu59:12 - How to cope with disappointment?1:11:06 - Is it difficult to say no?1:16:09 - OTT appreciation1:24:09 - Being a father1:28:25 - Relationship with social media1:34:29 - Director's actor1:38:51 - Executing a script is difficult1:41:55 - Shambala1:47:39 - Drinking career1:49:17 - Hostage movies1:53:00 - Four aspects

PJ chats to Dave McCarthy of AADI.ie Hosted on Acast. See acast.com/privacy for more information.

Modi's Master Plan: Pakistan, Oil & The Rise of India | Dhurandhar & Unknown Gunmen | Aadi Achint

Pakistan's GAME OVER! | Action on Illegals on Eastern Borders | Aadi Achint, Sanjay Dixit

Send us a textRamesh and Kathy reacto to the trailer for Aadi Shambhala A Mystical World  When a meteor crashes into the highly superstitious village of Shambhala in the 1980s, strange supernatural events unfold, forcing an atheist scientist to face an ancient horror-one that science can't explain or escape.When a meteor crashes into the highly superstitious village of Shambhala in the 1980s, strange supernatural events unfold, forcing an atheist scientist to face an ancient horror-one that science can't explain or escape.Support the show

Unknown sent by Modi to Bangladesh? | Chicken Neck | Pakistan | Trump v Ukraine | Aadi Achint

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

Game Over for Pakistan? | Maj Gen Rajiv Narayanan, Sumit Peer, Abhijit Iyer Mitra, Aadi Achint

What is Modi Government Planning? | Delhi Blasts & Inside News | Mulla Munir & Pakistan |Aadi Achint

What is Modi Government Planning? | Delhi Blasts & Inside News | Mulla Munir & Pakistan |Aadi Achint

Tilak Devasher, Col RSN Singh, Aadi Achint, Col.Ajay Raina on The Shifting Geopolitics of South Asia

What is Modi Planning? | Military Exercises & NoTAMs | Bangladesh Collapse | Pak | Aadi Achint

Pakistan Breakup — Countdown Has Begun! | Spygames in Bangladesh & Modi's Assasination | Aadi Achint

Pakistan Breakup — Countdown Has Begun! | Spygames in Bangladesh & Modi's Assasination | Aadi Achint

Setbacks for Trump | Pakistan Cheats Again | Pakistan Geography to Change | China |  Aadi Achint

Modi's Big Actions and Crackdown | Sonam Wangchuk in Jail | Amit Shah | Pakistan | Trump|Aadi Achint

H1-B Visa Bomb by Trump - Target India? | Pak in Turmoil | Bangladesh, China, Manipur | Aadi Achint

Nepal is a Big Warning to Modi? | Qatar, Israel | Aadi Achint, Sanjay Dixit

This week's bonus podcast is all about Aadi Alahan. Introduced to the show as a newborn baby in 2006, Aadi's now officially flown the nest and headed off to start a new life in India (and yes, he's somehow 20 now - some of these soap character really do grow up so fast!). From his days as a budding golf prodigy to dodgy dates, steamy affairs, and being wrongly accused of spiking Lauren, Aadi's storylines have kept us thoroughly entertained over the years. But what were our most memorable Aadi moments? And what was it about his character that made him such a fan favourite? Join us as we look back on the highs, lows, and hidden gems of Aadi Alahan's time on the Street in our latest character profile!

On our latest podcast, we chat about the episodes of Coronation Street shown in the UK between the 25th and the 29th August (Episodes #11,653 - 11,658). Sorry, we couldn't help it - this episode does get somewhat ranty towards the beginning thanks to Corrie's insane decision to publish spoilers about the massive twist in Friday's episode first thing in the morning, thus ruining the surprise for anyone foolish enough to scroll social media rather whilst munching on their Weetabix rather than switching straight to ITVX. And it was a great twist too! Definitely something that we're interested in seeing the fallout from at Number 13... Anyway, that wasn't even the main focus of the week - that particular spotlight, of course, falls on Asha, who had a bit of a mare of a day to flash back to on Monday, and on the same week that we're saying goodbye to the lovely Aadi, too! Also this week, Theo ramps up his control of Todd when he bans him from seeing Billy, whilst over at the Rovers - praise be! - Christina's back in town, and Jenny's feeling more than a little suspicious of her motives...  Up next on the podcast it's The Kabin, and we chat a bit about Adam Hussain's latest short film, Spice For Life, which made its way onto YouTube this week, and we round off the show with some feedback, including one listener's personal ranking of all the Rovers owners over the years - now that's a discussion we can really get behind! Street Talk - 00:13:26 The Kabin - 03:02:45 Feedback - 03:12:48

Tariff Trump Shocker by US Court | Selling Diesel to Ukraine | Modi Changing World ft. Aadi Achint

On our latest podcast, we chat about the episodes of Coronation Street shown between the 18th - 22nd August (Episodes #11,647 - 11,652). There was definitely something in the Weatherfield water this week as everyone seemed to be more than a little bit randy! From Steve and Cassie (and an unwilling third party teddy bear) cavorting in the living room of Number 9 to Sarah-Louise using her best seduction techniques on Underworld's latest client, the cobbles were practically steaming - and as for Abi and Carl's saucy antics.. well we can definitely say we were pleased to see Tracy pouring a bucket of cold water over that on Friday! Also this week, we had Aadi deciding that a trip to India maybe isn't  such a bad idea after all, romance between Dee-Dee and Olly, and an some intriguing comments from Costello that had us theorising all sorts about the circumstances surrounding Becky's death... After the Street Talk segment of the podcast, we were off to The Kabin, where we take a look at which cast members have been nominated for an NTA this year, and we finish things off with some lovely listener feedback. Street Talk - 00:10:57 The Kabin - 02:05:24 Feedback - 02:15:25

This podcast covers episodes 11,647 to 11,652. When Kit accosts a badly parked motorist, he sets a remarkable chain of events into action. Steve buys apology lager for Tyrone but then gets in his bad books again by giving him a show no one wants to see. Carl has to think quick when he finds Tracy in his hotel room, ready for action. Dee Dee is conflicted about a romantic opportunity with one of her clients. Tim and Sally are shocked to learn that Brody had plans to abscond with his sisters. Aadi decides that moving to India might be for the best, while Asha hides an upsetting incident at work. Olly's a midnight creeper. Tracy's a lurker. Costello is baffling.

On our latest podcast, we chat about the episodes of Corrie shown between the 11th and the 15th August (Episodes #11,641 - 11,646). We were a bit tight for time when we were recording this as we had a wedding to get to, so this episode is Street Talk only! This week saw Abi and Carl come dangerously close to being exposed when Hope inadvertently snapped a photo of them together in the precinct. Sadly for us, one impromptu phone dunking later and their secret's still safe… Can this affair just end or be rumbled soon, please, Corrie? Meanwhile, Gary dishes out a dose of street justice to Noah after hearing how he treated Theo in the past – but with Danielle pointing the finger at her husband for the attack, it looks like his chances of seeing his kids again are slipping away. Also this week, Steve makes himself less than welcome when he moves into Number 9, things go from bad to worse for Aadi, and George suffers an unsuccessful blind date – though could romance be waiting just a corner shop away?

This podcast covers episodes 11,641 to 11,646. Todd reckons Theo is playing games with him and decides to give him a taste of his own medicine. Carla makes tentative plans to take her relationship with Swain to the next level. Steve's furious to find that Tracy has been lying about the valuation of the florists. After not hearing from Eileen since she left, George is encouraged to get himself back in the dating game. An afternoon of passion for Aadi and Amy is ruined by Lauren who is out for revenge. Dee Dee worries that the time she spends working means she's missing out on Laila's development milestones. A cheeky photo of Tyrone could end up spelling trouble for Carl and Abi's secret affair. Gary hates pamphlets. David barks all night. Dorin is a top hider.

On our latest podcast, we chat about the episode of Coronation Street shown between the 4th and the 8th August (Episodes #11,635 - 11,640). This week's trip to the cobbles saw Dev booted and turquoise-suited for his wedding to Bernie – and naturally, it wouldn't be a Weatherfield wedding without a few dramatic curveballs thrown in, would it? Vomiting quads! A break-in at Number 7! An asthma attack at the altar! And one very big revelation from Aadi that puts a serious dampener on Dev's big day... Elsewhere, Todd uncovers some rather shocking skeletons in Theo's closet, leaving us not wondering 'if' he'll end up on the receiving end of a knuckle sandwich from his new fella – but 'when'. Meanwhile, Abi and Carl continue their hotel hook-ups, Jenny turns her attention to a rather unexpected new man, and Carla and Lisa settle into life at Number 6. Up next on the podcast, it's the Kabin, with some good news for overseas viewers wanting to catch Corrie early, then after another chunk of listener feedback, we share our thoughts on some very spoilery casting news that broke this week - and we're pretty flippin' excited! Street Talk - 00:11:38 The Kabin - 02:28:42 Listener Feedback - 02:38:37 Kabin Extra - 3:05:03

This podcast covers episodes 11,635 to 11,640. Abi and Carl throw caution to the wind as they embark on a steamy tryst in a room of a hotel owned by Abi's sister-in-law. Sally and Tim are concerned when they discover bruises on Shanice's arms. Carla and Swain move into number six and immediately have themselves a lodger. Theo and Todd are excited when the flat above the Corner Shop becomes available. Tracy and Steve reach a truce in their divorce settlement. After fixing a leaky O ring, George is seen in a new light by Jenny. As the wedding approaches, Auntie Rani continues to look down her nose at the whole affair. Aadi shouldn't drink. Sarah makes things worse. Ryan has nightmares of Victorian dolls.

Modi's Surgical Strike on Trump | The Ultimate Showdown Between Modi vs Trump vs Putin | Aadi Achint

India Didn't Just Win — It Humiliated Pakistan & America | Trump, China & Modi | Aadi Achint Podcast

India Didn't Just Win — It Humiliated Pakistan & America | Trump, China & Modi | Aadi Achint Podcast

This podcast covers episodes 11,629 to 11,634. Abi and Carl succumb to their lustful desires for five minutes in the garage office. Todd and Theo declare their love for each other after an uncomfortable fumble in the back seat of a Ford Fusion. James is heartbroken when Dee Dee announces she's decided to be a mum for Laila after all. Bernie does her best to keep Dev away from the wedding planning and particularly the budget. Sam enacts his revenge on Lily by concocting a story about a spate of nuanced burglaries in the area. Swain skips therapy and remains caught in the shadow of Becky's potential corruption. Aadi loves a spreadsheet. Billy is a nosy vicar. Jack makes beans.

Modi vs Trump vs Pakistan | Modi Ignoring Trump is a Masterstroke | Aadi Achint Finds Pak Oil Fields

Sanjay Dixit and Aadi Achint uncover the buried truth of Noor Khan: a nuclear base split between American oversight and Chinese tech. As bunkers burn and data leaks erupt, Pakistan's air dominance collapses.

This podcast covers episodes 11,623 to 11,628. Bernie is keen that Aadi maintains his lie about the robbery at the Corner Shop. Noah's back and wastes no time trying to encourage Theo to a conversion therapy session. Carla feels helpless as she tries to support Swain through her therapy. Lou has one last throw of the dice as she tries to avoid a lengthy jail term for twatting Gary. Tensions are high between Sam and Lily following the lockdown incident at the school. Carl's loan sharks are circling while he looks to Debbie for salvation. Audrey loves the drama. David mistrusts air fryers. Ryan read a book.

Trump Angry Over Modi's Free Trade with UK | Pak in Crisis as Drone Attacks Increase | Aadi Achint

We're not going to be able to record at all this weekend, so Episode #690 of the podcast is coming out early, focusing on what went on in Weatherfield on the 21st and the 23rd July (Episodes #11,623 - 11,626). It was a tough week for Theo this week when Noah reared his head again with a Bible in one hand and a leaflet to his latest conversion session in the other. Can Theo let go of his past and stay true to himself? Also this week, Ryan's left reeling when Debbie gives him an unexpected kiss - a friendly gesture from a grateful boss, a side effect of her dementia.. or something much murkier? Meanwhile, Aadi scrambles to keep Dev from uncovering the truth about the staged robbery, Lou braces herself for a likely prison sentence, and Sam mysteriously vanishes during Audrey's birthday party. Could Lily's antics last week be to blame? Not much in the way of Corrie news this week so we give The Kabin a swerve, and finish off with a couple of pieces of listener feedback. Street Talk - 00:11:24 Feedback - 01:50:39

On our latest podcast, we chat about the episodes of Coronation Street shown between the 14th and the 18th July (Episodes #11,617 - 11,622) Another big event episode this week – and yes, another prison break and another hostage situation. This time, it was Mick's turn in the spotlight, but how did it measure up to recent rampages? And did Corrie really need to return to that same well so soon after Rob Donovan's escape? Meanwhile, Lily's got a new head and, with it, a brand new attitude – but was her callousness towards Sam during the school break-in in any way justified? Also this week, Aadi and Brody stage a robbery, there's a gazump-off between Lisa and Carla, and while Gary's head might be healing, his pride has taken a serious hit... Up next, we take a quick trip to The Kabin, where we chat about the competition launches by This Morning to get a Corrie fan's pooch a walk-on part in the show, and we round off the week with more of your feedback.  Street Talk - 00:14:39 The Kabin - 02:37:51 Feedback - 02:44:54

This podcast covers episodes 11,617 to 11,622. In retrospect, it turns out that it was a really bad idea to let a man on remand for killing a police officer work in the prison laundry. Brody is devastated when both paternal figures in his life reject him on the same afternoon. Nick is furious when he discovers that Lily kept Sam locked out of a safe room during the incident at the school. Debbie causes concerns when she puts in an offer £30,000 over the asking price for Number 6. Gary discharges himself from hospital and at home he reacts badly to a bit of banter from Liam. Aadi cooks up a hare-brained scheme to regain the money he lost that time he over-ordered whisky. Hope's worried for Chesney. Lauren's got new lippy. Sarah huffs Kit's oxters.

Col Ajay Raina, Aadi Achint, Sanjay Dixit on Pakistan, China, America | Deep Insights on World Order

On our latest podcast, we discuss the episodes of Coronation Street shown on the 10th and the 11th July (Episodes #11,613 - 11,616). This week's episodes finally saw the reveal of what happened to Gary the night of the party to put him into the coma - and to the surprise of no-one, it's Lou who's right at the heart of it. Will she be able to talk her way out of this one? Meanwhile, Lisa starts her therapy sessions and finds herself opening up a lot more than she was expecting about Becky. Also this week, Lauren and Aadi get closer, an insecure Kevin continues to lie about his health, and Dee-Dee gets Laila christened in secret. Next up on the podcast, it's The Kabin, and we chat about the nominations for this year's Inside Soap Awards. We finish things off with more of your fantastic feedback. Street Talk - 00:11:26 The Kabin - 01:51:36 Feedback - 02:13:56

This podcast covers episodes 11,609 to 11,616. Todd confronts Millie about his suspicions of her pregnancy. Kev is worried about the gulf growing between him and Abi and contrives a foolhardy plan to keep her. Dee Dee has trouble respecting the boundaries of the adoption agreement with James. Steve panics when he lets slip that he's falling for Cassie. Aadi feels responsible for Racist Kelly when she is finally released from hospital. Conflicted by Tinker and Becky's deaths, Swain struggles to open up during her first therapy session. Maria's concerns for Gary grow while Nina continues to worry about her own involvement. Fiz can't change a flat. Jack takes a penalty. Carla puts cheese in her bath.

India is Preparing For Something Big? | Importance of Skardu for India | Col Ajay Rina, Aadi Achint, Sanjay Dixit

We're now six months into 2025, which can only mean one thing – it's time for our Coronation Street mid-year review! It's been a dramatic start to the year, with a string of big exits – from Mason's tragic death to Daisy's glamorous escape to Bali – but is Corrie shedding too many characters at once? We dive into the growing trend of event episodes, including the Platt house fire, Mick and Kit's powerful flashback, Aadi's ill-fated party and more. Plus, we discuss the arrival of the Michaelis family, the surprise return of Rob Donovan, and what the increased reliance on those hospital and police sets might mean for the show's future. No stone is left unturned in our deep dive into Corrie's 2025 so far!

This podcast covers episodes 11,603 to 11,608. Brody and his new best friend Dylan crash the party at Number 7 and take along a little something-something to get things moving. Racist Kelly worries she's universally hated then has her drink accidentally spiked at the party. Steve and Cassie are an item and Tracy congratulates them by making some ridiculous divorce demands. Debbie doesn't take too kindly to Kev and Ronnie sticking their noses into how she will be cared for in the future. Todd is shocked when he discovers Millie drinking lager in the community garden. Nina tries to remember details of the troubling events after the party, while Maria wonders where on earth Gary's disappeared to. Kit's so done with this week. Aadi's a disappointing snog. Summer is a hoot.

On our latest edition of the podcast, we chat about the episodes of Corrie shown between the 16th and the 20th June (Episodes #11,597 - 11,602) This week saw Glenda putting on a drag night at the Rovers - but the real drag was most definitely Theo, who Todd seems to be besotted with despite him having more red flags than the Swiss embassy. Meanwhile, the truth about Debbie's condition comes out on Friday and she does a runner - does the fact that she doesn't turns up on the Victoria Gardens bench by the end of the episode mean we're in for a longer term missing person story? Also this week, Lou locks lips with Gary, Aadi plans a Summer party and Dee-Dee and James clash over her plans for a religious upbringing for Laila. Up next on the podcast is The Kabin, where we share our thoughts on the reports that Jack Carroll has quietly left the show, and we finish things off with a bumper feedback session. Street Talk - 00:23:49 The Kabin - 02:41:03 Feedback - 02:53:01