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Dr. Jasmine Sukumar and Dr. Dionisia Quiroga discuss advances in adjuvant therapy for patients with early breast cancer and BRCA1/2 mutations, including how to identify patients who should receive genetic testing and the significant survival benefits of olaparib that emerged from the OlympiA trial. TRANSCRIPT Dr. Jasmine Sukumar: Hello, I'm Dr. Jasmine Sukumar, your guest host of the ASCO Daily News Podcast today. I'm an assistant professor and breast medical oncologist at the University of Texas MD Anderson Cancer Center. On today's episode, we'll be exploring advances in adjuvant therapy for high-risk early breast cancer in people with BRCA1/2 germline mutations. Joining me for this discussion is Dr. Dionisa Quiroga, an assistant professor and breast medical oncologist at the Ohio State University Comprehensive Cancer Center.  Our full disclosures are available in the transcript of this episode.  Dr. Quiroga, it's great to have you on the podcast. Thanks for being here. Dr. Dionisia Quiroga: Thank you. Looking forward to discussing this important topic. Dr. Jasmine Sukumar: Let's start by going over who should be tested for BRCA1/2 genetic mutations. How do you identify patients with breast cancer in your clinic who should be offered BRCA1/2 genetic testing? Dr. Dionisia Quiroga: So, guidelines on who to offer testing to somewhat differ between organizations at this point. I would say, generally, I do follow our current ASCO-Society of Surgical Oncology (SSO) Guidelines, though. Those guidelines recommend that BRCA1/2 mutation testing be offered to all patients who are diagnosed with breast cancer and are 65 years old or younger. For those that are older than 65 years old, there are additional factors to really take into account to decide on who to recommend testing for. Some of this has to do with personal and family history as well as ancestry. The NCCN also has their own specific guidelines for who to offer testing to. For example, people assigned male at birth; those who are found to have a second breast primary; those who are diagnosed at a young age; and those with significant family history should also be offered BRCA1/2 testing.  I think, very important for our discussion today, ASCO and SSO also made a very important point that all patients who may be eligible for PARP inhibitor therapy should be offered testing. So clearly this includes a large amount of our patient population. In my practice, we often refer to our Cancer Genetics Program. We're fortunate to have many experienced genetic counselors who can complete pre-test and post-test counseling with our patients. However, in settings where this may not be accessible to patients, it can also be appropriate for oncology providers to order the testing and ideally perform some of this counseling as well. Dr. Jasmine Sukumar: Thank you Dr. Quiroga. Let's next review where we are in current clinical practice guidelines. What current options do we have for adjuvant therapy specific to people with high-risk early breast cancer and BRCA1/2 genetic mutations? Dr. Dionisia Quiroga: Our current guidelines recommend adjuvant olaparib for one year for individuals with HER2-negative high risk breast cancer. This approval largely came from the data and the results of the OlympiA trial. This was a prospective phase 3, double blind, randomized clinical trial. It enrolled patients who had been diagnosed with HER2-negative early-stage breast cancer who also carried germline pathogenic or likely pathogenic variants of either the BRCA1 and/or BRCA2 genes. The disease also had to be considered high-risk and there were several criteria that had to be evaluated to deem whether or not these patients were high-risk. For example, those who are treated with neoadjuvant chemotherapy, if they had disease that was triple-negative, they needed to have some level of invasive residual disease at time of surgery. Alternatively, if the disease was hormone receptor-positive, they needed to have residual disease and a calculated CPS + EG score of 3 or higher. This scoring system is something that estimates relapse probability on the basis of clinical and pathologic stage, ER status, and histologic grade, and this will give you a score ranging from 0 to 6. In general, the higher the score, the worse the prognosis. This calculator though is available to the public online to allow providers to calculate this risk.  For the subset of patients who received adjuvant chemotherapy, for them to qualify for the OlympiA trial, if they had triple-negative disease, they needed to have a tumor of at least 2 cm or greater and/or have positive lymph nodes for disease. For hormone receptor-positive disease that was treated with adjuvant chemotherapy, they were required to have four or more pathologically confirmed positive lymph nodes at time of surgery. From this specified pool, patients were then randomized 1:1 to get either adjuvant olaparib starting at 300 mg twice a day or a matching placebo twice a day after they had completed surgery, chemotherapy and radiation treatment if needed. Dr. Jasmine Sukumar: And what were the outcomes of this study? Dr. Dionisia Quiroga: The study ended up enrolling over 1,800 patients and from these 1,800 patients, 70% had a BRCA1 mutation while 30% had a BRCA2 mutation. About 80% of the patients had triple-negative disease compared to hormone receptor-positive disease. Interestingly, about half of all patients enrolled had received neoadjuvant chemotherapy while the other half received adjuvant chemotherapy.  Looking at the outcomes, this was overall a very positive study. We actually now have outcomes data from a median of about 6 years out. This was just reported in December at the 2024 San Antonio Breast Cancer Symposium. There was found to be a 9.4% absolute difference in six-year invasive disease-free survival favoring the olaparib arm over the placebo arm. What was also interesting is that this was consistent across multiple subgroups of patients and the benefit was really seen whether or not they had hormone receptor-positive or triple-negative disease. The absolute difference in distant disease-free survival was also high at 7.8% and additionally favored olaparib. Most importantly, there was found to be a significant overall survival benefit. The six-year overall survival was 87.5% in the olaparib group compared to 83.2% in the placebo group. This translates to about a 4.4% difference and a relative 28% overall survival benefit in using olaparib.  Now, future follow up is going to be very important. Follow up for this study is actually planned to continue out until June 2029 so we can continue to observe if these survival curves will continue to branch apart as they have so far at each follow up. And I think this is especially important for those patients diagnosed with hormone receptor-positive cancers because we know those patients are at particular risk for later recurrences.  As an additional side note, the researchers also noted that there were fewer primary malignancies in the olaparib group, not just of the breast but also primary ovarian or fallopian tube cancers as well, which is not completely surprising knowing that this drug is also heavily used and beneficial in different types of gynecologic cancers. Ultimately, the amount of adverse events reported have been low with only about 9.9% of patients receiving olaparib needing to discontinue drug due to adverse events, and this is compared to 4.2% reported in the placebo group. Dr. Jasmine Sukumar: You mentioned that the OlympiA trial showed an overall survival benefit, but interestingly the OlympiAD trial looking at olaparib versus chemotherapy in patients with advanced metastatic HER2-negative breast cancer did not show a significant overall survival benefit. Could you discuss those differences? Dr. Dionisia Quiroga: I agree, that's a very good point. So OlympiA's comparator arm was, of course, a placebo. So while this isn't the same as comparing to chemotherapy, it does still potentially suggest that there is a degree of benefit that olaparib can provide when it's introduced in the early local disease setting compared to advanced metastatic disease. I think we need more future trials looking at potential other combinations to see if we can improve the efficacy of PARP inhibitors in the metastatic setting. Dr. Jasmine Sukumar: For patients who do choose to proceed with use of adjuvant olaparib due to the promising efficacy, what side effects should oncologists counsel their patients about? Dr. Dionisia Quiroga: The most common notable side effects, I would say with olaparib and other PARP inhibitors are really cytopenias. Gastrointestinal side effects such as nausea and vomiting can occur as well as fatigue. There are some less common but potentially more serious side effects that we should counsel our patients on. This includes pneumonitis. So counseling patients on if they're short of breath or experiencing cough to let their provider know. Venous thromboembolism can also be increased rates of occurrence. And then of course myelodysplastic syndromes or acute myeloid leukemia is something that we often are concerned about. That being said, I think it should be noted that interestingly in the OlympiA trial so far, there have been less new cases of MDS and AML in the olaparib group than actually what's been reported in the placebo group at this median follow up of over six years out. So we'll need to continue to monitor this endpoint over time, but I do think this provides some reassurance. Dr. Jasmine Sukumar: Since the initiation of the OlympiA trial, other adjuvant treatments have also been studied and FDA approved for non-metastatic HER2-negative breast cancer. So for example, the CREATE-X trial established adjuvant capecitabine as an FDA approved treatment option in patients with triple-negative breast cancer who had residual disease following neoadjuvant chemotherapy. So if a patient with triple-negative breast cancer with residual disease is eligible for both adjuvant olaparib and adjuvant capecitabine treatments, how do you decide amongst the two? Dr. Dionisia Quiroga: If a patient's eligible for both, I honestly often favor olaparib, and I do this because I find the data for adjuvant olaparib a little bit more compelling. There are also differences in toxicity profile and treatment duration between the two that I think we should discuss with patients. For example, olaparib is supposed to be taken for a year total, whereas with capecitabine we typically treat for six to eight cycles with each cycle taking three weeks. There are some who may also sequence the two drugs in very high-risk disease. However, this is very much a data free zone. We don't have any current clinical trials really comparing these two or if sequencing of these agents is appropriate. So I don't currently do this in my own clinical practice. Dr. Jasmine Sukumar: Nowadays, almost all patients with stage 2 to 3 triple-negative breast cancer will be offered neoadjuvant chemotherapy plus immune checkpoint inhibitor therapy pembrolizumab per our KEYNOTE-522 trial data. With our current approach, pembrolizumab is continued into the adjuvant setting regardless of surgical outcome, so that patients receive a year total of immunotherapy. So in patients with residual disease and a BRCA germline mutation, do you suggest using adjuvant olaparib concurrently with pembrolizumab? Do we have any data to support that approach? Dr. Dionisia Quiroga: I do. I do use them concurrently. If a patient is eligible for adjuvant olaparib, I would use it the same way as if they were not on pembrolizumab. That being said, there are no large studies currently that have shown what the benefit or the toxicity of pembrolizumab plus olaparib are for early-stage disease. However, we do have some safety data of this combinatorial approach from other studies. For example, the phase 2/3 KEYLYNK-009 study showed that patients with advanced metastatic triple-negative breast cancer who were receiving concurrent pembrolizumab and olaparib had a manageable safety profile, particularly as the toxicities of these drugs alone don't tend to overlap. Dr. Jasmine Sukumar: And what about endocrine therapy for those that also have hormone receptor-positive disease? Dr. Dionisia Quiroga: Adjuvant endocrine therapy should definitely be continued while patients are on olaparib if they're hormone receptor-positive. An important component of this will also likely be ovarian suppression, which should include recommendation of risk reducing bilateral salpingo oophorectomy due to the risk of ovarian cancer development in patients who carry BRCA1/2 gene mutations. In most cases, this should happen at age 40 or before for those that carry a BRCA1 mutation, and at age 45 or prior for those with BRCA2 mutations. Dr. Jasmine Sukumar: And do you also consider adjuvant bisphosphonates in this context? Dr. Dionisia Quiroga: Yes. Like adjuvant endocrine therapy, adjuvant bisphosphonates were also instructed to be given according to standard guidelines in the OlympiA trial, so I would recommend use of bisphosphonates when indicated. You can refer to the ASCO Ontario Health Guidelines on Adjuvant Bone-Modifying Therapy Breast Cancer to guide that decision in order to utilize this due to multiple clinical benefits. It doesn't just help in terms of adjuvant breast cancer treatment but also reduction of fracture rate and down the line, improved breast cancer mortality.  Dr. Jasmine Sukumar: Particularly in hormone receptor-positive breast cancer, another adjuvant therapy option that was not available when the OlympiA trial started are the CDK4/6 inhibitors, ribociclib and abemaciclib, based on the NATALEE and monarchE studies. So how do you consider the use of these adjuvant therapy drugs in the context of olaparib and BRCA mutations? Dr. Dionisia Quiroga: Yeah, so we are definitely in a data-free zone here. And that's in part because the NATALEE and the monarchE studies are still ongoing and reporting data out at the same time that we're getting updated OlympiA data. So unlike some of our other adjuvant treatments that we discussed, where olaparib could be safely given concurrently, the risk of myelosuppression and using both a CDK4/6 inhibitor and a PARP inhibitor at the same time would be too high. In some cases, even if a patient has a BRCA1/2 mutation, they may not meet that specified inclusion criteria that OlympiA set for what they consider to be high-risk disease. And we know from the NATALEE and the monarchE trial there are also different markers that they use to denote high-risk disease. So it's possible, for example, in the NATALEE trial that looks specifically at adjuvant ribociclib, they included a much larger pool of hormone receptor-positive early-stage breast cancers, including a subset that did not have positive axillary lymph nodes.  In cases where patients would qualify for both olaparib and a CDK4/6 inhibitor, I think this is worth a nuanced discussion with our patients about the potential benefits, risks and administration of these drugs. I think another point to bring up is the cost associated with these drugs and the length of time patients will be on for, because financial toxicity is always something that we should bring up with patients as well. When sequencing these in high-risk disease, my practice is to generally favor olaparib first due to the overall survival data. There is also some data to support that patients with BRCA1/2 germline mutations may not respond quite as well to CDK4/6 inhibitors compared to those without. But again, this is still outside of the purview of current guidelines. Fortunately, we have more potential choices for patients, and that's a good thing, but shared decision making also needs to be key. Dr. Jasmine Sukumar: And while our focus today is on adjuvant treatment for people who carry germline BRCA mutations, what about other related gene mutations such as PALB2 pathogenic variant? Dr. Dionisia Quiroga: That's a great question. Clinical trials in the advanced metastatic setting have shown that there is efficacy of olaparib in the setting for PALB2 mutations. This is largely based on the TBCRC 048 phase 2 trial and that provided a Category 2B NCCN recommendation for patients with these PALB2 gene mutations. However, we're really still lacking enough clinical data for use in early-stage disease, so I don't currently use adjuvant olaparib in this case. I am definitely eager for more data in this area as the efficacy of PARP inhibitors in PALB2 gene mutations is very compelling. I think also, in the same line, there's been some data for somatic BRCA1/2 mutations in the metastatic setting, but we still have a lack of data for the early stage setting here as well. Dr. Jasmine Sukumar: Thank you Dr. Quiroga, for sharing your valuable insights with us today on the ASCO Daily News Podcast. Dr. Dionisia Quiroga: Thank you, Dr. Sukumar. Dr. Jasmine Sukumar: And thank you to our listeners for your time today. You'll find links to the 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. 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. Dionisa Quiroga @quirogad @quirogad.bsky.social Dr. Jasmine Sukumar @JasmineSukumar  @jasmine.sukumar.bsky.social Follow ASCO on social media:  @ASCO on X   @ASCO on Bluesky    ASCO on Facebook    ASCO on LinkedIn    Disclosures: Dr. Dionisia Quiroga:  No relationships to disclose Dr. Jasmine Sukumar: Honoraria: Sanofi (Immediate Family Member)  

Listen to Karen's interview of Shachar Oren, of Sound Media Ventures, as he shares his journey from boot strapped startup to successful exit to lead a Media Tech VC firm in Atlanta, GA.  Karen first met Shachar nearly 2 decades ago when he was raising capital for Neurotic Media and wanted to present to her angel group, the Network of Business Angels & Investors.   Shachar's  journey as an entrepreneur gave him keen insights into the concepts of growth hacking, lean start up, boot strapping, raising capital, and getting to a profitable exit.  His experience has provided an unique perspective as an angel investor and venture capitalist sitting on the opposite side of the table.   Shachar also shares his insights as to what he looks for when considering investments in the emerging field of Media Tech.  Enjoy their conversation and learning moments.  Shachar Oren is the Founder & CEO of Sound Media Ventures, a venture capital firm that invests in companies at the nexus of media and technology. Prior to starting this fund, Shachar founded Neurotic Media, a high-tech music platform that served global Fortune 500 brands for 18 years. Shachar led the successful exit of Neurotic Media to Peloton Interactive in 2018. For the last decade, Shachar has also offered executive counsel pro bono for incubators, educators, and start-up founders. He currently serves as the President of Georgia Music Partners, and advises startups in technology, media and entertainment through organizations such as TechStars Music, GA Tech's Create-X and College of Creative Design, ATDC, GSU Main Street among others.  He is a member of Atlanta Technology Angels and active in the growing entrepreneur/investor ecosystem in Georgia.   For more information please visit: https://soundmedia.vc/ Karen Rands is the leader of the Compassionate Capitalist Movement™ and author of the best selling investment primer: Inside Secrets to Angel Investing: Step-by-Step Strategies to Leverage Private Equity Investment for Passive Wealth Creation.  She is an authority on creating wealth through investing and building successful businesses that can scale and exit rich.  Karen is an enthusiastic speaker on these topics for corporations, economic development groups, angel investor networks, and professional  business networks.   About Karen https://www.karenrands.co/about-karen-rands/ Visit http://Kugarand.com and click on the Services tab, to learn more about the Compassionate Capitalist Wealth Maximizer System™.  Read about the Due Diligence Services, Investor Relations, Capital Strategies, Capital Access, and Capital Readiness Coaching serviced offered by her firm, Kugarand Capital Holdings.  The Compassionate Capitalist Show™ is a Podcast on YouTube.  Please visit and subscribe and share.  It is great to watch Karen and her guests live, in action.  The whole library of podcasts and interviews since 2020 can be found there by category or chronological. https://bit.ly/CCSyoutubepod   Imagine the feeling of investing in a way that had massive impact and a potential pay you back 10x your money. The time is now to find out if Angel Investing / CrowdFunding Investing is the wealth creation strategy for you.  Take action on Karen's offer to learn how to invest with confidence in entrepreneurs and sign up (FREE FOR NOW) the new Compassionate Capitalist Wealth Maximizing System. http://dothedeal.org  

Introduction: Welcome to Five & Thrive: a weekly podcast highlighting the Southeast's most interesting news, entrepreneurs, and information of the week, all under 5 minutes.  My name is Jon Birdsong and I'm with Atlanta Ventures.  Product Release of the Week: Who doesn't love a good product release and this week, after much anticipated industry coverage, Greenzie has pushed a major update to their software. Quick reminder about Greenzie, they are a software company that makes commercial lawn mowers autonomous. They have partnered with manufacturers including Wright Manufacturing and Bobcat to build the mowers with a few more bells and whistles so they can be activated into autonomous mowers. Landscapers love them, especially landscapers who mow big, wide open fields. This week, Greenzie launched a major update to their software including: Job saving and reloading: Map an area once and mow all season with the press of a button on an easy-to-use interface with no app download required. So now a lawn maintenance company can mow the perimeter of a property once and it's saved in the database so you don't have to mow the perimeter again. Before, you had to mow the perimeter each time. Not any more. Another major feature is job continuation. If your mower or job was interrupted now you can pick up where you left off with ease. Before it would start over from the beginning. These are huge workflow updates along with several other enhancements! Congrats to the Greenzie engineering team on delivering to the market.    Quiet Giant of the Week: This company just moved their HQ to 999 Peachtree Street which is 10th and Peachtree, right where Empire State South used to be. The name of the company is called FIXD Automotive. They have approximately 40 employees led by CEO, John Gattusso. Fixd is a hardware and software company that offers drivers the tools and resources that produce money saved and peace-of-mind over the life of their car. Their FIXD Sensor, which works with any gas-powered car since 1996 relays car problems from the vehicle to the FIXD App via Bluetooth. With the FIXD sensor, now you can translate 7000+ engine codes into plain English on your smartphone, see how severe your issue is, access detailed repair guides and how-to videos, monitor the health of multiple vehicles, and receive automated maintenance alerts. FIXD started out of Create-X and has been a Quiet Giant, growing steadily and quietly for years.  Question of the Week: We've been getting asked a bunch recently, what is Atlanta Ventures take on Artificial Intelligence? There is no question AI is a transformative evolution in technology. There will be several jobs and roles augmented and alleviated. From a pure consumer perspective, we are users of ChatGPT and Dall-E2 and explore those applications often. When it comes to pure investment in the space, it all depends on how AI is being applied. For example, last week, we invested in AdPipe out of Athens, Ga. They are Motion-First marketing platform that goes and finds specific types of clips in your video library, clips them into 2 second gifs, makes it easy to add overlays and copy, and then packages them up so marketers and sales reps now have a motion-first, customized piece of content. The engineering team is leveraging AI to find those specific clips. For example, one of their most well-known clients is Caterpillar. AdPipe now uses AI to find “videos of tractors” in Caterpillar's video library and within 30 seconds, AI has gone in and found dozens of videos from years of investment and delivered it to the AdPipe platform. Before AI, someone manually would have to go into the Caterpillar library, watch a lot of video for a few seconds to find tractor clips, clip it, and then upload it to AdPipe. Not anymore. One other point around narrative and storytelling on the fundraising side to highlight with AdPipe; they didn't brand themselves as a Generative-AI marketing platform when we first engaged with them. They were already solving a very real problem in the market with dozens of industrial customers. Instead, they are using AI to improve a specific use case and workflow. If we met a company that had no customers, limited product or revenue, and they positioned their product as an Generative-AI marketing platform, this is when our spidey senses would have heighted and immediately questioned if this was a spin on a piece of innovative technology looking for a problem to solve. All said and done, when it comes to AI, make sure the problem being solved is a real pain point and apply it smartly – a good example is the AdPipe product.  Annnnd that is five minutes! Links discussed: 

Oncologists love pushing the limits of what is possible for our patients. To celebrate this and the 20th episode of Oncology for the Inquisitive Mind, Michael and Josh explore the heights of pioneering treatment for early-stage triple-negative breast cancer (TNBC). A notoriously resistant cancer with no known targetable lesions that affect younger women on average, The BrighTNess trial, Keynote 522 and Create-X show just how far the treatment landscape has changed in the last five years.Tune into our final episode for the year! We will return in early 2023 with more content, interviews and hilarious banter.On a final note, Dr Michael Fernando has been admitted to the Royal Australian College of Physicians (RACP), the equivalent of being board certified! Michael has completed this arduous training and is now a fully-fledged Medical Oncologist! Do not distress listeners. Despite no longer being a trainee, Michael will continue on as presenter and host extraordinaire for this podcast.Links to studies discussed in this episode (subscription may be required):BrighTNess trial: https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30111-6/fulltextKeynote 522: https://www.nejm.org/doi/full/10.1056/NEJMoa1910549Create-X: https://www.nejm.org/doi/full/10.1056/NEJMoa1612645For more episodes, resources and blog posts, visit www.inquisitiveonc.comFind us on Twitter @InquisitiveOnc!If you want us to look at a specific trial or subject, email us at inquisitiveonc@gmail.comArt courtesy of Taryn SilverMusic courtesy of AlexiAction: https://pixabay.com/users/alexiaction-26977400/Disclaimer: This podcast is for educational purposes only. If you are unwell, seek medical advice. Hosted on Acast. See acast.com/privacy for more information.

Atlanta influencer turned founder Cynthia Ruff is building Hashtag Pay Me, the software helping creators and influencers appropriately price content. Incubated in Georgia Tech's startup accelerator Create-X, Cynthia is building her startup from over a decade of content creation experience. In this energetic episode, learn why she turned down early investor capital to bootstrap Hashtag Pay Me, the evolution of the creator economy, her thoughts on the current state of the growing creator economy, and what monetization opportunities lie ahead for creators.

While working in the cybersecurity industry for Cisco, Founder Henry Zhang became aware of critical gaps that large cybersecurity corporations overlooked when it came to the security posture and safety of local businesses. He and co-founder Nicole Wraback, a Georgia Tech computer science engineering grad who studied AI, decided to invent a solution that could work for real people. They enrolled in Georgia Tech's Create-X student accelerator and met Robin Bienfait, of Valor. He then went through Startup Runway, Valor's pre-seed investor introduction platform. Valor led Senteon's seed round, which also had participation from Lytical Ventures and Purdue. Senteon's cybersecurity platform allows stakeholders to audit endpoint behavior and identify system-level settings that can be implemented on in-production machines to provide "best-case" system hardening. While many competitors in the space are only touching part of the process and still requiring some manual output, Senteon's platform creates baselines specifically tailored to the granular needs of each business unit, spending only a fraction of the time previously needed to achieve greater efficacy. Henry explains it why Senteon is different and how it helps in this fascinating conversation with Valor investor William Leonard.

Georgia Tech leads the world in the number of startups launched, behind only Standard and MIT. Part of the magic is Create-X, a unique university accelerator that teaches students to build real businesses. Meet the man behind Create-X since 2019, Rahul Saxena, a GT grad himself with a robotics and genetics engineering background who's also worked as a VC, got an MBA from Emory, and experienced a turn-around as an operator. You'll hear how Georgia Tech sees "evidence based entrepreneurship." What Saxena says is, "You can actually teach entrepreneurship. It's a process." Don't miss this engaging interview with Valor investor William Leonard and learn all the tips Rahul has for starting great tech firms and the process of becoming a founder.

Rahul Saxena, Associate Director at Georgia Tech CREATE-X Rahul has a blend of deep technical and business experience that serve him well in his role as a Venture Capitalist. During undergrad at Georgia Tech, he conducted research by the age of 19 on mechanical heart valves that was later published and praised by the FDA. […] The post Rahul Saxena With Georgia Tech CREATE-X appeared first on Business RadioX ®.

Why should a surgeon care about breast cancer chemotherapy trials? Join Drs. Michael Alvarado, Rita Mukhtar, and Alexa Glencer as they discuss the benefits of neoadjuvant chemotherapy over upfront surgery and the role of adjuvant chemotherapy for select patients who harbor residual disease at the time of surgery. Learning objectives: - Understand the benefits conferred by neoadjuvant chemotherapy compared to upfront surgery in certain patients with breast cancer - Learn about the study design and results of the CREATE-X phase 3 randomized controlled trial comparing adjuvant capecitabine to standard therapy in patients with HER2 negative invasive breast cancer with residual disease following cytotoxic neoadjuvant chemotherapy - Describe the specific benefit of adjuvant capecitabine for triple negative breast cancer patients and discuss its evolving role with recent FDA approval of neoadjuvant pembrolizumab in this group - Learn about the study design and results of the KATHERINE phase 3 randomized controlled trial comparing adjuvant T-DM1 to trastuzumab in patients with HER2+ invasive breast cancer with residual disease following cytotoxic and HER2-targeted neoadjuvant chemotherapy Journal article links: CREATE-X: https://www.nejm.org/doi/full/10.1056/NEJMoa1612645 KATHERINE: https://www.nejm.org/doi/full/10.1056/NEJMoa1814017 Please visit behindtheknife.org to access other high-yield surgical education podcasts, videos and more.  

Episode summary introduction: Prof Raghupathy Sivakumar is the Founding Director of CREATE-X at Georgia Tech. Prof Sivakumar joins us on our podcast today to share Why CREATE-X was born , the structure, instruction and opportunities it offers, startups it helps launch and how students and faculty benefit from it. In particular, we discuss the following with him: Prof. Sivakumar's Professional Background Origins of CREATE-X The Entrepreneurial Confidence Program Benefits for Students and Faculty Topics discussed in this episode: Introducing Prof Sivakumar, Georgia Tech [] Prof. Sivakumar - Professional Background [] Joining Academia [] Startup Experiences [] Innovation - Siva's Take [] What is CREATE-X? [] Origins of CREATE-X [] Structure [] Student Stats [] Faculty Involvement [] Cross Disciplinary [] Success Stories [] Measuring Success [] Dealing with Failure [] What's Ahead for CREATE-X [] Culture Change at Georgia Tech [] Advice for Tomorrow's Innovators [] Wrap Up [] Our Guest: Raghupathy Sivakumar is Wayne J. Holman Chair Professor with the School of Electrical and Computer Engineering at Georgia Tech. He is also the Founding Director of CREATE-X at Georgia Tech. Prof. Sivakumar has a Bachelor's in Computer Science from College of Engineering, Guindy, India, and a Masters and PhD in Computer Science from University of Illinois Urbana Champaign. Memorable Quote: “...creating a network of people that you can tap into when you're ready to take the entrepreneurial plunge, right, because entrepreneurship by nature, you are always going to be limited by the resources that you have, right?” Prof Sivakumar advice to tomorrow's innovators & entrepreneurs. Episode Transcript: Please visit Episode's Transcript. Calls-to-action: Subscribe to our Weekly Podcast Digest. To Ask the Guest a question, or to comment on this episode, email podcast@almamatters.io. Subscribe or Follow our podcasts at any of these locations:, Apple Podcasts, Google Podcasts, Spotify, RadioPublic, Breaker, Anchor. For Transcripts of all our podcasts, visit almamatters.io/podcasts.

Dr. Hope Rugo, professor of medicine and director of Breast Oncology and Clinical Trials Education at the University of California, San Francisco Helen Diller Comprehensive Cancer Center, highlights key studies in breast cancer featured at the 2021 ASCO Annual Meeting.   Transcript: ASCO Daily News: Welcome to the ASCO Daily News podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. My guest today is Dr. Hope Rugo. She is 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. Dr. Rugo joins me to discuss key advances in the breast cancer field featured at the 2021 ASCO Annual Meeting. Dr. Rugo has received research support for clinical trials through the University of California from Pfizer, Merck, Novartis, Lilly, Roche, and other organizations. Her full disclosures are available on the transcript of this episode at asco.org/podcasts. Dr. Rugo, it's great to have you on the podcast today. Dr. Hope Rugo: Oh, it's great to be here. ASCO Daily News: There were many interesting studies in breast cancer featured at the Annual Meeting. Thank you for being here to highlight some of them. Let's start with the OlympiA trial. This is LBA1. This remarkable study found that adjuvant olaparib extends disease-free survival in BRCA-mutated early stage HER2-negative breast cancer. What can you tell us about this trial? Dr. Hope Rugo: Well, this is really such an amazing study, in terms of the results and its practice-changing impact. The study actually kind of interestingly was published in the New England Journal [of Medicine] 2 days before it was presented. And even though we had all seen the data, it was really such a, I think, moving presentation in terms of really changing the face of treatment for women and men with BRCA1 and BRCA2 associated breast cancer. Of course, olaparib and talazoparib are both PARP inhibitors that are approved to treat metastatic breast cancer associated with BRCA1 and BRCA2 mutations. And in those randomized trials, they showed improvement in response and progression-free survival, but not clear differences in overall survival. So, of course, when we have an impact in the metastatic setting, the next step is to move into early-stage breast cancer. But that's quite a challenge given the fact that you have to test and find the mutation, which is challenging in some parts of the world. And then you have to decide which group of patients need more than standard therapy. So the OlympiA trial randomly assigned patients who had pathogenic BRCA1 or BRCA2 mutations and HER2-negative, either hormone receptor-positive or triple negative breast cancer, to receive a year of olaparib or a placebo. And the patient eligibility was further defined. If you had triple negative breast cancer, you could have had any residual disease after neoadjuvant therapy, or you had to have a tumor greater than two centimeters or a positive node. If you have hormone receptor-positive disease keeping in mind the benefit of adjuvant endocrine therapy. If you didn't have a pathologic complete response to neoadjuvant therapy, you had to have a few other high-risk features using the CPS plus EG score. And if you received adjuvant therapy, you had to have four or more positive nodes, so stage III disease. All patients had to have received at least six cycles of chemotherapy, radiation as indicated, and of course, hormone therapy was given for hormone receptor-positive disease. There were over 1,800 patients randomly assigned, which was pretty, I think, impressive given the fact that everybody had to be tested. And the whole idea behind the trial is that you would enroll a group of patients who still had a high residual risk of recurrence, even though you got standard and reasonable adjuvant or neoadjuvant therapy. It's important to keep in mind when you think about the results of this trial is that having a BRCA mutation, and in particular BRCA1, increases sensitivity to chemotherapy. So the pathologic complete response rates, for example, in the neoadjuvant setting for triple negative breast cancer with the BRCA1 gene mutation, are higher than in patients who don't have a germline mutation. And so you're really looking at a group of patients who have high-risk disease because they didn't have a pathologic complete response if it was the neoadjuvant setting. Now, of the patient population, a little over 70% had BRCA1 mutations. The rest had BRCA2 mutations. And for the triple negative group, that represented a large portion of the population, about 80%. Again, the rest, a little under 20%, had hormone receptor-positive disease. As you would expect, more than 50%, about 60%, were premenopausal. And about 50% received neoadjuvant therapy. There's always a question about whether or not treatment with prior platinum-based therapy, which is also effective when you have DNA repair deficiency, such as in the germline BRCA mutations, whether or not that would affect sensitivity. A little more than a quarter of the patients had received a platinum chemotherapy agents. And the invasive disease-free survival, the primary endpoint of this trial, was really remarkable. There was an 8.8% improvement in a 3-year invasive disease-free survival rate in patients taking olaparib versus placebo, a very big p-value, and a hazard ratio 0.58. This is really dramatic. The curves separated early, and they remained separated. So that it was the IDFS was 77% for patients on placebo and about 86% in patients who were receiving olaparib, just really very impressive. And one of the things you want to find out about is are you changing the rate of distant recurrence. And indeed, not only were there less distant recurrences, but if you look at distant excluding the brain, that's where you really saw the biggest difference. There was a small difference--hard to know if it really is significant--1.5% less brain recurrence is a big issue for patients, particularly with triple negative disease. It was a little less contralateral invasive disease, but it wasn't anything significant. So really, what you were preventing was the kind of recurrence we don't want to see, which is distant recurrence. And then if you looked at the distant disease-free survival, the absolute improvement for metastatic disease was 7.1%. Again, the curve separated early and stayed separated over time. Now, overall survival, of course, is the golden endpoint that you want to look at. There were numerically less deaths in the olaparib arm, 59 versus 86 in the placebo arm. Most of these deaths were due to breast cancer. And the hazard ratio is 0.68. Although the p-value was 0.024, that didn't meet the statistical plan, which was a p less than 0.01 in terms of how the statistics can be balanced in this trial. But the overall difference was 3.7%. And of course, there were subgroup analyses done, which showed that everybody benefited. It was impossible to see a difference. And again, only a small number of patients relatively receive platinum, so it's hard to know whether or not that changed the response. In terms of the side effects--you always want to think about side effects--it was exactly what you would have expected from what we [expect] in the metastatic setting. Not a lot of grade III or greater toxicities. Mainly anemia was the most common at 9%, and 5% neutropenia, a little bit increase of grade III fatigue, but only 2%. The rest of the toxicities were all grade I and II. And of note, olaparib does cause nausea, 57% of patients versus 23% reported nausea with olaparib versus placebo. But normally, you can manage this nausea and the anemia by actually dose reducing and first holding and then dose reducing. One of the big questions, of course, with PARP inhibitors is if you're inhibiting repair of DNA, are you causing leukemia--new primary cancers? And it was very encouraging. Again, it's 3 years, so we need to be followed a little bit longer, maybe 5, but it was 0.2% or 0.3%. There was no increase in myelodysplasia or myeloleukemias with the use of the PARP inhibitor, which is really important. And the global quality of life scores were identical. So even with these side effects, they could be managed and didn't impact global quality of life. And then in terms of the paper, the additional information the paper gave is that most of the people who required a transfusion received only one transfusion of red blood cells. So I think with the caveat that there are some additional side effects, they are generally able to be managed well. Quality of life is maintained. And there's a huge early difference in the most important endpoints that we look for in these trials--invasive disease-free survival and most importantly, distant disease-free survival. So definitely history in the making. ASCO Daily News: Excellent. Thank you for sharing these fantastic results from the OlympiA trial. The ECOG-ACRIN Research Group presented EA1131, a study of platinum-based chemotherapy or capecitabine in patients with residual triple negative basal-like breast cancer following neoadjuvant chemotherapy (Abstract 605). This interim analysis really highlighted the need for better therapies for this patient population. What are your thoughts on this trial? Dr. Hope Rugo: Well, this, I think, is an important trial. Ingrid Mayer from Vanderbilt designed the trial with ECOG and actually presented the data. There will be a lot more data coming from this study because they collected tumor tissue and are doing a lot of different analyses, which might help us understand the benefits of different treatments in different subgroups of patients with triple negative breast cancer. Now, this trial really focused on patients who have the highest risk disease after neoadjuvant therapy, clinical stage II or III triple negative breast cancer diagnosis. They received the standard neoadjuvant chemotherapy. And they had to have tumors that were greater than one centimeter in the breast at the time of surgery or any positive lymph nodes. So this is actually a group of patients who we already know have a high-risk of distant recurrence. They did do an analysis of the tissue using a PAM50 assay to understand which tumors were basal or non-basal like. And patients were randomly assigned to receive capecitabine by the CREATE-X trial, which showed an improvement in overall survival when capecitabine was given to patients with residual triple negative breast cancer after neoadjuvant chemotherapy in Japan and Korea, versus carboplatin or cisplatin by treating physician discretion (DOI: 10.1056/NEJMoa1612645). The patients received four cycles every 3 weeks of carbo or cisplatin. Now, one thing that's important to keep in mind is in Japan where the CREATE-X trial was designed in Korea where it also participated, the capecitabine dose was the original U.S. Food and Drug Administration (FDA)-approved dose, where it was a little bit higher, 1,200 milligrams per meter squared twice a day, 2 weeks on, 1 week off. In the U.S., patients don't tolerate this very well. And there is a different metabolism in Asian patients, where they can tolerate a higher dose of 5FU and capecitabine with not as much toxicity due to pharmacogenomics. The patients in the ECOG-ACRIN trial received capecitabine at 1,000 milligrams per meter squared twice daily with the same schedule, which is really all that's tolerated. So the objective of this trial was to see whether or not you could do better or the same if you received a platinum versus capecitabine with the idea that DNA damaging agents work very well in basal-like triple negative breast cancer. So the patients were enrolled in this trial. 415 patients were randomly assigned. And then the data safety monitoring group who were following the results at the interim analysis ended up closing the trial because they found that based on the statistics so far that it was unlikely that the platinum arm would either be better or worse than the capecitabine arm. And they saw more toxicity in the platinum arm. So the trial was closed. And that's the data that was presented. So there was a total of 160 patients who received capecitabine, [and] 148 [patients] who received platinum. Most of the patients had basal-like disease. The age, it was about 52. It's all what you would have expected to see in this patient population. So I don't think we have any concerns about the patient population. The 3-year invasive disease-free survival in patients with basal-like triple negative breast cancer, the primary endpoint of the trial, was identical between the two arms. But actually, discouragingly, it wasn't great. So IDFS for capecitabine was 49% and platinum 42%. So this was actually very disappointing data. And I think it just highlights how we really need to provide better treatment for our patients who don't achieve pathologic complete responses to the best neoadjuvant therapy. It is true that the ECOG-ACRIN trial didn't require that patients receive anthracyclines, but 85% did. So I think that we feel really comfortable that they got good chemotherapy. They looked in the non-basal-like sub-type. And in the non-basal-like sub-type, which are cancers that are more likely to be responsive to capecitabine in the metastatic setting, actually, the outcome, although small numbers, looked better with capecitabine than with getting the platinum-type therapy. And if you looked at non-basal versus basal, regardless of therapy, the patients who had non-basal-like disease did much better than the patients who had basal-like disease, something that we would have guessed, but hasn't been shown before. So I think it was really important, [and] really helps us to identify the patients who need the most intervention. But even the basal group, the IDFS, the non-basal group, it was 55.5%. So better than basal at 46%, but still you got 45% of patients with invasive disease-free survival event over a 3-year medium follow-up. Overall survival at 3 years, also, was disappointing at about 66% for capecitabine and 58% for platinum. So I think that, really, this trial just identified, I think, in a very confirming way how we need to make progress in the treatment of these patients who have residual disease after neoadjuvant chemotherapy. In terms of toxicity, the platinum-based therapy clearly was more toxic. Most of the toxicity that was seen was grade I and II, as you would expect, but there was more grade III toxicity even with the platinum-type therapy. Again, as you would expect. You get hand-foot syndrome with capecitabine and not with platinum. But there was more of the standard toxicities that you would expect with the platinum or bone marrow suppression, primarily some thrombocytopenia, et cetera. So when they looked overall at the trial population, I mentioned that most had basal sub-type by PAM50. It was 80%. So it is a group of patients where I think even going into neoadjuvant therapy about 80% have basal-like disease. So I think it makes us very interested in the results that we expect to see in the very near future from the KEYNOTE 522 trial, where we've seen an improvement in pathologic complete response, particularly in patients with node positive disease with the addition of pembrolizumab, to standard taxane platinum and anthracycline-based neoadjuvant chemotherapy (DOI: 10.1056/NEJMoa1910549).  But a very recent press release noted that they have reached their event-free survival endpoint. And that pembrolizumab improves event-free survival. And the importance of this data, which, of course, has not yet been shared, so we have to see what it looks like and what the differences are, is that they had shown earlier at the FDA's ODAC meeting in February of this year that possibly patients who don't achieve a PCR, who received pembrolizumab before and after surgery, had a better outcome than patients who did not receive pembrolizumab and received placebo. So how we incorporate capecitabine into the post-neoadjuvant treatment or other novel agents will very much be a subject of the next few years as we sort this out. But if the pembrolizumab data is indeed exciting--and we'll talk more about the durvalumab data in just a moment--then I think the question would be, what chemotherapy do you give? And based on this trial, there is absolutely no indication for platinum postoperatively in patients with residual disease after neoadjuvant therapy. Capecitabine should be given. But clearly, we need better options for therapy. And this is also being studied with some of the new antibody drug conjugates, like sacituzumab govitecan to see whether or not we can improve outcome in these patients. ASCO Daily News: Right. Well, let's look at Abstract 506. This is the phase II GeparNuevo study. The data presented by the German Breast Group showed that neoadjuvant durvalumab improves long-term outcomes for patients with triple negative breast cancer. What is your takeaway from this study? Dr. Hope Rugo: You know, this was really interesting, and I think unexpected results based on their original presentation. This was a phase II neoadjuvant trial in patients with triple negative breast cancer. And the data by the GBG and Sibylle Loibl, who runs the GBG, had already presented the data from the primary endpoint of this smaller neoadjuvant trial, which was pathologic complete response. And what they did in this trial was they treated patients with a nab-paclitaxel followed by epirubicin and cyclophosphamide. And the patients were randomly assigned to receive the checkpoint inhibitor durvalumab versus placebo. There were 174 patients stratified by a low, medium, or high TILs. And their main endpoint, as I mentioned, was PCR. So this is a secondary endpoint of invasive disease-free survival. A group of patients received 2 weeks of durvalumab as sort of a lead-in first. And they've looked at that group separately. But it's hard to know because it's such a small trial what that means. And nobody is using a lead-in right at the moment. So their primary endpoint, as I mentioned, has been published already in Annals of Oncology in 2019 (DOI: 10.1093/annonc/mdz158). Although numerically there was a higher PCR rate in the durvalumab treated arm, this was not statistically significant. The p-value is in no way significant. And they looked at, in a forest plot, they showed that the patients who had the window seemed to have a higher PCR, but it was hard to justify exactly why that was the case in this group of patients. Now, it's important to keep in mind that the data that we have from KEYNOTE 522, the neoadjuvant trial with pembrolizumab, and IMpassion 31, the trial with the atezolizumab, showed the benefit, particularly in patients with node-positive disease. In this trial, about a third of the patients had stage zero or I breast cancer. So 61 out of the total of 174 patients did not have positive nodes. So we thought the PCR difference really wasn't seen because they had a low-risk population. But now, they're presenting their secondary endpoint of invasive disease-free survival in this group of patients. And what they saw, actually, at a median follow-up of about 44 months, they saw a 12 IDFS events in the durvalumab arm and 22 in the placebo arm. And actually, there were twice as many distant recurrences in the patients treated with placebo versus durvalumab. So 13 versus six events for distant recurrence. So I think that's actually a really important endpoint. And if you looked at the invasive disease-free survival at 3 years, it was 77% for placebo and almost 86%. So almost a 9% difference in favoring the patients who received durvalumab. Pretty dramatic, you know? A hazard ratio of 0.48. And they did have a p-value of 0.0398. So that was quite interesting. And they looked at distant disease-free survival. Numbers are small here, but I think it's a really important endpoint, and overall survival. Overall survival is early to see, but they could see--this is a long follow-up, but it's a small study rather than early--and they showed that overall survival difference was 83.5% in the placebo arm and 95.2% in the durvalumab arm. Again, secondary endpoints with a hazard ratio is 0.24 and, again, a p-value of 0.1. Distant disease-free survival, such an important endpoint, was a huge difference 78.4% versus 91.7%. Again, hazard ratio of 0.31. So pretty dramatic. And when you looked at subgroups of patients, and they looked at PD-L1 positive versus negative. Almost all of the patients had PD-L1 positive disease, so 138 versus 20 that were PD-L1 negative. So it's kind of hard to interpret any of that. And that trial was stratified by stromal TILs anyway. They did show that patients who had a PCR had a better outcome than patients who did not have a PCR. But among the patients who had a PCR, the patients who had durvalumab did better, again, with almost a 10% difference, favoring durvalumab versus placebo. Now, this is a phase II randomized trial, so it's small. And so this is really hypothesis generating. But given the fact that KEYNOTE 522 and IMpassion 31 (NCT03197935) gave the checkpoint inhibitor for a year, and in this situation patients received durvalumab only in the neoadjuvant setting, it suggests that they saw this impact in patients who had a PCR that was greater in patients receiving durvalumab placebo. So it suggests that even though the PCR improvement was not significant, that just the treatment with a checkpoint inhibitor changes long-term outcome. And we know that there's more toxicity by giving longer course checkpoint inhibitor therapy, so we expect that we might see approval of pembrolizumab based on the KEYNOTE 522 trial. And it will bring up the question of whether or not you need a whole year of treatment to improve outcome. And whether or not simply treatment preoperatively might be sufficient, particularly in the patient group who achieves a PCR. It will be, I think, very, very important to be able to evaluate this in order to reduce the toxicity, both the physical toxicity, as well as financial toxicity from use of checkpoint inhibitors in patients with triple negative breast cancer. Also, we know that a third of these patients had stage I disease. And I think we really need to look at the larger trials quite carefully to understand whether or not all patients need checkpoint inhibitors who have triple negative disease. Or whether or not we could more correctly focus on the patients who have higher risk disease, node-positive disease who've been shown to have less tumor infiltrating lymphocytes than patients who have less burdensome disease at diagnosis. ASCO Daily News: Right. So what about the subset analysis in Abstract 1011 that looked at outcomes in patients who are age 65 and older in the phase III ASCENT study of sacituzumab in metastatic triple negative breast cancer? Can you tell us about ASCENT and the toxicities associated with this antibody drug conjugate in this older patient population? Dr. Hope Rugo: Well, ASCENT, of course, is a practice-changing trial as well. It led to the final formal approval of sacituzumab govitecan for patients with metastatic triple negative breast cancer in the second line or greater earlier this year after accelerated approval was granted earlier in 2020. This antibody drug conjugate is given 2 weeks on, 1 week off. And the primary toxicity is neutropenia, and then to a lesser degree diarrhea. But overall, the drug is quite well-tolerated. In the overall parent ASCENT trial, as the listeners know, showed an improvement in progression-free and overall survival at the first analysis. Very impressive data with sacituzumab in these heavily pretreated triple negative breast cancer population, compared to treatment of physician choice with standard chemotherapy options, where about 50% of the patients received eribulin, which had already been shown to be better in terms of overall survival compared to other chemotherapy in the subset of patients treated in the past with eribulin who had triple negative disease. So at ASCO this year, Kevin Kalinsky presented on behalf of our authorship group a subset analysis looking at patients who were age 65 and older to better understand whether there was more toxicity and as much benefit in this group of patients. So important when we're looking at novel therapies. So overall, there were 44 patients treated with sacituzumab and 46 with treatment of physician choice who were age 65 or older. Most of the patients had received two to three lines of therapy. And about 40% had received greater than three lines of therapy. The median prior anticancer regimen was pretty similar to the overall group. Most of the patients had initially been diagnosed with triple negative disease, but really, interestingly, about a third of the patients had ER-positive or something else disease initially and were triple negative on biopsy in the metastatic setting. So an interesting subgroup of patients that were also looked at separately and appeared to benefit to the same degree as the triple negative patients. So we looked at progression-free survival in this group of patients looking at patients under age 65 and age 65 and older. A hazard ratio was even greater in the age 65 or older for--it's hard. These are subset comparisons, but the hazard ratio is 0.22 going from 2.4 months with standard therapy to 7.1 months with sacituzumab. The hazard ratio in the younger group was 0.46. But still a big difference in progression-free survival. And then in terms of overall survival in the age 65 and older group, it went from 8.2 to 15.3 months with a hazard ratio of 0.37. And so also really quite dramatic. And overall response was also significantly increased with, in fact, the only responses seen in the age 65 or older group seen in the sacituzumab group. There were no complete or partial responses in the treatment of physician choice group. Of course, really important to look at safety in our older patients because we know that generally there is more toxicity in that group of patients. But actually looking at grade III or greater toxicity, keeping in mind it was 49 [patients] in the older group versus 209 patients in the younger group, there was no difference in grade III or greater toxicities. There were more dose reductions. So 35% reduced their dose versus 19% older versus younger. But there was no difference in adverse events that led to discontinuation between the younger and older group. So that was really encouraging. We see this in almost all trials that older patients have more dose reductions and that was seen here as well. And we also looked at this very small subset of patients who are age 75 or older versus age 65 or older. And the rates of adverse events were similar, albeit smaller number of patients. There was, if you looked at specific treatment-related adverse events that led to dose reduction, it was a neutropenia, fatigue, diarrhea, febrile neutropenia in a small number, 6% versus zero in the treatment of physician choice and nausea. So it's helpful to know what those toxicities are when you're thinking about treating these patients in clinical practice. And in a patient who might be a little less strong, a little older, more comorbidities, so slightly more frail, I would consider starting potentially at a 3/4 of the dose and then going up if they tolerate it well, versus starting at the full dose and getting a lot of toxicity. But this was really encouraging data that showed that you can give the drug to patients who are older and even elderly at age 75 or greater. So that was good to see. And then Lisa Carey presented additional data looking at patients who were treated in the second line or greater because the formal approval by the FDA is in second or greater line. But most of the data looked at patients who were treated in the third or greater line. So you were supposed to have at least two chemotherapies for advanced disease, but you could have had one in the early stage setting if your progression occurred within 12 months. So there were 33 and 32 patients in the sacituzumab and treatment of physician arm, respectively, who had a recurrence within 12 months of neo or adjuvant chemotherapy. They got one line of chemotherapy in the metastatic setting. And then they were randomly assigned on the ASCENT trial. And as you would expect, tiny numbers, right? 33 and 32 patients. But you get a lot of events in this patient population. The PFS was much greater in patients getting sacituzumab than treatment of physician choice. Hazard ratio of 0.41. And also, if you looked at overall survival, it was double. The hazard ratio is 0.51, even in the second line setting. I think it's really interesting to look to see what the toxicity is relative to the lines of therapy. But because the numbers are so small, it's really hard to look at this now. We'll see more data on toxicity when we see data in the first line, as well as the post-neoadjuvant setting in ongoing trials. And I think that will help us a lot to understand what I think we see in the current clinical trials and in practice, which is that patients who are treated in this second line setting have less hematologic toxicity as well as GI toxicity and need less growth factor intervention, et cetera. And I expect that we'll see that in the post-neoadjuvant setting as well. These numbers are too small to really look at any differences in toxicity. But all of this data I think was incredibly encouraging for us in terms of the use of sacituzumab in patients with metastatic triple negative disease, as well as the expansion to the first line and to post-neoadjuvant setting. ASCO Daily News: Excellent. Investigators of the phase III MINDACT trial, that's Abstract 500, evaluated the survival of patients with an ultra low risk 70 gene signature. How will MINDACT inform clinical practice? And do you think this study might guide more appropriate choices of chemotherapy in women with node-negative or one to three node-positive disease? Dr. Hope Rugo: Well, how MINDACT will inform clinical practice is a very big question. And it already has informed clinical practice identifying patients who are better candidates for chemotherapy and endocrine therapy versus endocrine therapy alone who have stage I and II hormone receptor-positive early stage breast cancer based on their primary outcome results. This particular analysis was something different. So we think about using this 70 gene score and the recurrence score from the TAILORx trial (DOI: 10.1056/NEJMoa1804710) and RxPONDER to try and identify which patients need more therapy versus less therapy. Now, we also know that these scores have some prognostic impact. Clinically, we mainly have used them to decide who should get chemotherapy in addition to endocrine therapy. This trial looked at a different way to use a gene expression scoring system. It's really to identify which patients need less. Given the fact that your middle of the line therapy is endocrine therapy, which patients do we know who will do very, very well with any endocrine therapy and don't need extended duration endocrine therapy? That's really the question here. So they looked at the patients who were in the MINDACT trial and used data published by my colleague, Laura Esserman who looked at a cohort of patients retrospectively and found that patients who had an ultra low score in MINDACT. And that's a score greater than 0.355 where plus 1 is the lowest end of low risk, and minus 1 is the highest end of high-risk, so greater than 0.355. She identified a group of patients who did well, regardless of whether they received tamoxifen or not apparently in this retrospective long-term outcome where there was 15-year follow-up. So they use that data to go into the MINDACT population and to try and understand which patients benefit. And the MINDACT is a much higher risk group of patients. So if you looked at that original trial that Laura Esserman published, these patients had screen detected cancers. And in fact, the 70 gene signature low and ultra low-risk tumors are, as you would expect, over-represented in screen detected cancers. So you've got this excellent survival regardless of treatment. So how did they apply to MINDACT? So in MINDACT, patients were randomly assigned, of course, who had clinical low, genomic high, or clinical high genomic low to receive chemotherapy or not. In this situation, you're really looking at the patients who have genomic ultra low disease. So most of those patients would not be getting chemotherapy because they would already have ultra low disease. So what they found actually when they looked at the overall population of MINDACT, 6,700 or so patients, they found 15% of patients or 1,000 patients fell into this ultra low category. And if then you looked at the patients who were high-risk, it was 36%. And patients who fell into the big low-risk group, it was about 49%, so about half of the population of patients. So they looked at the different metastasis-free interval rates in patients who had genomic low and ultra low-risk disease, regardless of the treatment the patients receive. They all receive endocrine therapy, remember? So they actually found that in patients who were ultra low versus low-risk, that the hazard ratio is 0.65, showing that patients who had ultra low-risk--remember, this was 1,000 patients at 8 years--there was only 36 events. So they had a 97% 8-year distant metastasis-free interval, compared to 94.5% for low-risk and 89.2 in high-risk disease. They looked at breast cancer-specific survival rates as well. And for ultra low-risk in 1,000 patients, there were exactly eight events. 99.6% 8-year breast cancer-specific survival. So really, quite remarkable. So clinical high-risk tumors tend to have larger size, higher grade, be node-positive. We already know that. For the 1,000 genomic ultra low-risk patients, about almost 70% were greater than 50 years. 80% were node negative. 81% had tumors that were T1, so up to two centimeters. And most of them, except for 4%, were grade I and II. 97% were hormone receptor-positive HER2-negative. Only 14% of patients who had ultra low-risk disease received chemotherapy in MINDACT. And most of the rest received endocrine therapy. Some actually didn't receive endocrine therapy. 16% had no adjuvant systemic treatment at all. So if you looked at the genomic ultra low-risk patients and divided them into clinical low-risk and clinical high-risk, there was really no difference in the events overall, a little bit less 8-year distant metastases-free survival, but not much of a difference. So really, a quite remarkable outcome. Now, what you want to know, of course, then is, does it make a difference if you get endocrine therapy at all? And they looked at the patients who had chemotherapy versus no chemotherapy. And as you would expect, it made no difference. Again, it was a tiny number of patients. But if you looked at endocrine therapy versus no endocrine therapy, it was hard to tell. Because, again, no adjuvant systemic therapy was only 157 patients. There were four events. And for the patients, 685 patients who got endocrine therapy, there were 23 events. So the 8-year metastasis-free interval was identical, but there just aren't enough patients in that no adjuvant systemic therapy group to really understand. So what we know is ultra low-risk defines a group of patients who have excellent outcomes. Does it tell us that they don't need adjuvant systemic therapy? No. Eight years really isn't enough time, unfortunately, in is group because 50% of recurrences occur after five years and out to 20 plus years. We have to keep in mind the Early Breast Cancer Trials Group data showing how many recurrences occurred after five years of endocrine therapy. But in this group of patients who have ultra low-risk disease, they clearly do not benefit from chemotherapy. And I think that's regardless of their clinical risk. And it's likely that 5 years of adjuvant endocrine therapy is absolutely all those patients would ever need. If you have a small cancer that's ultra low-risk, could you get by with less than 5 years of endocrine therapy in a patient with a lot of toxicity? Potentially. And I think that's a really important bit of information to take back into clinical practice when you're talking to patients about the duration of endocrine therapy. But a stage I tumor or stage II with ultra low-risk disease, in general, I would treat for 5 years. I think it's important to keep in mind that premenopausal women, even with ultra low-risk stage II disease, have an ongoing risk of recurrence. And I still think that those patients should be treated with a varying function suppression and aromatase inhibitor if tolerated and tamoxifen otherwise because our very young patients tend to have higher risk of recurrence over time. And it's very hard to separate them out in these studies. Interestingly, there are a few young women who have ultra low-risk disease. So I think this really helps us understand yet another impact of genomic tests, which is who needs less therapy, not just who needs more. ASCO Daily News: Great. That's good to hear. Well, finally, the theme of the Annual Meeting was equity. And in Abstract 1092, you and your colleagues at University of California, San Francisco (UCSF) looked at decreased enrollment of patients with advanced lobular breast cancer compared to ductal breast cancer in interventional clinical trials. Can you tell us about this study? Dr. Hope Rugo: Yes, this was a really interesting evaluation. My colleague surgeon Rita Mukhtar at UCSF actually led this evaluation with a very good student who's working with us on some of our research trials. And the idea was that we had observed anecdotally, as have others, that patients with invasive lobular cancer tend to be less likely to meet criteria for clinical trials. So they don't have measurable disease as much. We tend to see sclerotic bone lesions, diffuse infiltration without measurable disease. And it can be much, much more difficult to meet the criteria for clinical trials. So actually, what my colleagues did in this trial is look at whether or not patients with lobular breast cancer are underrepresented in clinical trials. And so they looked at the proportion of interventional stage IV clinical trials that used RECIST in clinicaltrials.gov. And then actually looked at the patients who have RECIST measurable disease who have lobular cancer. And it's really interesting. I mean, we just have a lot less RECIST measurable disease. And in the UCSF cancer registry, patients who were enrolled in clinical trials, if you looked at invasive lobular cancer were markedly decreased if you compare it to patients with other sub-types of breast cancer. So we think that that's probably due to the requirement for measurable disease. And that what we should do in patients who have metastatic lobular cancer is develop trials that are specifically for lobular cancer that focus on the unique biology. And there's a lot of work going on now looking at that biology. And allow patients to enroll based on their disease control rates rather than response. So that we don't require RECIST measurable disease since that's hard to come by in invasive lobular cancer. So I think it's a really important area. It's about 15% of invasive breast cancers. We see a lot of lobular cancer in the metastatic setting. And I think it's unfortunate not to be able to enroll these patients in clinical trials. There is a lot of interest in the cooperative groups in the United States in Europe and in Asia, of course, in trying to do trials that are focused on addressing the needs of patients with lobular cancer, both in the early and late-stage setting. ASCO Daily News: Excellent. Thank you, Dr. Rugo. It's been great to have you on the podcast today. Thanks so much for sharing your valuable insight with us on the ASCO Daily News podcast. Dr. Hope Rugo: It was really a pleasure to participate and thank you for putting together these podcasts. ASCO Daily News: And thank you to our listeners for your time today. If you enjoyed this episode, please take a moment to rate and review us, wherever you get your podcasts.     Disclosures: Dr. Hope Rugo Honoraria: Puma Biotechnology, Mylan and Samsung Research Funding (Institution): Pfizer, Merck, Novartis, Lilly, Roche, Odonate, Daiichi, Seattle Genetics, Macrogenics, Sermonix, Boehringer Ingelheim, Polyphor, Astra Zeneca and Immunomedics. Travel, Accommodations, Expenses: Pfizer, Novartis, Mylan, AstraZeneca, Merck 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

Listen (or watch) as Shachar Oren of Sound Media Ventures shares his journey from boot strapped startup to successful exit to lead a Media Tech VC firm in Atlanta. Karen first met Shachar nearly 2 decades ago when he was raising capital for Neurotic Media and wanted to present to her angel group, the Network of Business Angels & Investors.  Shachar's journey as an entrepreneur gave him keen insights into the concepts of growth hacking, lean start up, boot strapping, raising capital, and getting to a profitable exit. His experience has provided an unique perspective as an angel investor and venture capitalist sitting on the opposite side of the table.  Shachar also shares his insights as to what he looks for when considering investments in the emerging field of Media Tech. Enjoy their conversation and learning moments. Shachar Oren is the Founder & CEO of Sound Media Ventures, a VC firm that invests in companies at the nexus of media and technology. Previously, Shachar founded Neurotic Media, a high-tech music platform that served global Fortune 500 brands for 18 years, and sold to Peloton Interactive in 2018.  Shachar serves as the President of Georgia Music Partners, and advises startups in technology, media and entertainment through organizations such as TechStars Music, GA Tech's Create-X, and GSU Main Street and active in the growing entrepreneur/investor ecosystem in Georgia.   For more information please visit: https://soundmedia.vc/ Karen Rands is a sought after adviser to entrepreneurs seeking capital and investors seeking help in evaluating angel investment opportunities.  Her book, Inside Secrets to Angel Investing and resource portal, is the best selling primer for new angel investors.  For more info, visit http://karenrands.co On Youtube: https://youtu.be/hMu5sVxKTsI  

Listen (or watch) as Shachar Oren of Sound Media Ventures shares his journey from boot strapped startup to successful exit to lead a Media Tech VC firm in Atlanta. Karen first met Shachar nearly 2 decades ago when he was raising capital for Neurotic Media and wanted to present to her angel group, the Network of Business Angels & Investors.  Shachar's journey as an entrepreneur gave him keen insights into the concepts of growth hacking, lean start up, boot strapping, raising capital, and getting to a profitable exit. His experience has provided an unique perspective as an angel investor and venture capitalist sitting on the opposite side of the table.  Shachar also shares his insights as to what he looks for when considering investments in the emerging field of Media Tech. Enjoy their conversation and learning moments. Shachar Oren is the Founder & CEO of Sound Media Ventures, a VC firm that invests in companies at the nexus of media and technology. Previously, Shachar founded Neurotic Media, a high-tech music platform that served global Fortune 500 brands for 18 years, and sold to Peloton Interactive in 2018.  Shachar serves as the President of Georgia Music Partners, and advises startups in technology, media and entertainment through organizations such as TechStars Music, GA Tech's Create-X, and GSU Main Street and active in the growing entrepreneur/investor ecosystem in Georgia.   For more information please visit: https://soundmedia.vc/ Karen Rands is a sought after adviser to entrepreneurs seeking capital and investors seeking help in evaluating angel investment opportunities.  Her book, Inside Secrets to Angel Investing and resource portal, is the best selling primer for new angel investors.  For more info, visit http://karenrands.co On Youtube: https://youtu.be/hMu5sVxKTsI  

First up we discuss RxPonder and what it adds to adjuvant treatment of breast cancer in the context of TailoRx. Then we discuss a recent study (https://jamanetwork.com/journals/jama/fullarticle/2774295)of additional capecitabine following adjuvant chemo in TNBC and what it adds in the context of CREATE-X.

Dr. Laws graduated from the University of British Columbia and obtained her medical degree from McMaster University. She completed a general surgery residency at the University of Calgary and a breast surgical oncology fellowship at Massachusetts General Hospital/Brigham and Women’s Hospital. She is currently pursuing a Master of Public Health in epidemiology from the Harvard T.H. Chan School of Public Health. She is a member of the Society of Surgical Oncology (SSO) and the American Society of Breast Surgeons (ASBrS). Dr. Laws’ clinical and research interests include optimizing oncologic outcomes after breast cancer surgery, improving cancer care delivery through implementation of evidence-based practices, as well as managing patients at high-risk for breast cancer. We were lucky enough to get her expertise about a number of important topics, including neoadjuvant therapy for breast cancer, indications for axillary node dissection in 2020, and an approach to recurrent breast cancer. Finally, we delve into her experience as a patient, and how that shaped her practice as a surgeon. Links: 1. Intraoperative Margin Assessment in Wire-Localized Breast-Conserving Surgery for Invasive Cancer: A Population-Level Comparison of Techniques. https://pubmed.ncbi.nlm.nih.gov/27406094/ 2. Does intra-operative margin assessment improve margin status and re-excision rates? A population-based analysis of outcomes in breast-conserving surgery for ductal carcinoma in situ. https://pubmed.ncbi.nlm.nih.gov/30293241/ Breast Biopsy During Post-treatment Surveillance of Screen-Detected Breast Cancer Patients Yields High Rates of Benign Findings. https://pubmed.ncbi.nlm.nih.gov/32100221/ 3. Margins in Breast-Conserving Surgery After Neoadjuvant Therapy. https://pubmed.ncbi.nlm.nih.gov/30128902/ 4. KATHERINE trial: https://www.nejm.org/doi/full/10.1056/NEJMoa1814017 5. CREATE-X trial: https://www.nejm.org/doi/full/10.1056/NEJMoa1612645 6. RX-PONDER: https://www.nature.com/articles/s41598-019-49644-6 7. The surgeon who underwent surgery: How being a patient changed him. https://www.kevinmd.com/blog/2019/10/the-surgeon-who-underwent-surgery-how-being-a-patient-changed-him.html

This week in the hot seat I am chatting with product design expert, Andrew Phelps, about how to create the right products within your business that will grow your bottom line! A lot of business owners think they don't have a product they can create and sell; but the fact is they just aren't thinking hard enough about their customers needs and interface. Every business, regardless of what you do, needs good products in order to attract the right leads that will ultimately grow revenue. We dive deep into the topics of: - How to create basic products within your everyday business that can reach more customers, and educate people about what you do! - Focusing on customer experience within your business; - What customers expect from every business in the digital age? - and much, much more! So what are you waiting for? Be Bold, Be Brave and Go Give Life a Crack!

Dr. Neelima Denduluri, a medical oncologist at Virginia Cancer Specialists and Associate Chair of the Breast Cancer Research for the US Oncology Network, discusses key abstracts in the breast cancer field that were featured at the ASCO20 Virtual Scientific Program.   Transcript ASCO Daily News: Welcome to the ASCO Daily News Podcast. I'm Geraldine Carroll, a reporter for the ASCO Daily News. Joining me today is Dr. Neelima Denduluri, a medical oncologist at Virginia Cancer Specialists and Associate Chair of Breast Cancer Research for the US Oncology Network. Dr. Denduluri serves on the editorial board of the ASCO Daily News, and will highlight key abstracts that were featured at the ASCO20 Virtual Scientific Program.   Dr. Denduluri has received institutional research funding from Amgen, Novartis, Genentech, Eli Lilly, Pfizer, Daiichi Sankyo, Seattle Genetics and Immunomedics. Full disclosures relating to all Daily News podcasts can be found on our episode pages. Dr. Denduluri, it's great to have you on the podcast today.   Dr. Neelima Denduluri: Thank you, Geraldine, for asking me to participate on the podcast.   ASCO Daily News: Let's start with advanced breast cancer. Can you tell us about the key abstracts that address this patient population?   Dr. Neelima Denduluri: Absolutely. So this year's ASCO was filled with many rich advancements across the therapeutic, diagnostic, and symptom management spectrum, which is always wonderful when we're trying to treat our patients adequately. In advanced breast cancer, one abstract that generated significant interest is whether surgery improves outcomes in patients that present with advanced breast cancer.   Generally, the paradigm in advanced breast cancer is to give systemic therapy. We've always wondered, does taking out the local site of disease or the primary tumor, in terms of the breast tumor and lymph nodes, and possibly giving radiation, does that improve outcomes in advanced breast cancer? Well, the late-breaking abstract 2 (LBA2), presented by Dr. Khan, looked at women or men who presented with stage IV de novo breast cancer. And these patients obviously started their appropriate systemic therapy based on the subtype of breast cancer.   And these patients, after three to six months, were randomized to continue the systemic therapy or stop their systemic therapy for local management before resuming their systemic therapy. And what the study showed is that those patients that did receive local therapy did not have an improvement in survival compared with those patients that did not receive local therapy to their breasts and/or lymph nodes. So I think that was an excellent lesson for all of us. And how it guides our management is to say that the vast majority of our patients with advanced breast cancer do not need to undergo surgery to improve outcomes. Now, having said that, about 25% of patients that did not have any local therapy did have some progression. And so for those patients, despite no improvement in long-term quality of life, it is something that we should consider and talk about with them. Especially if that is the only site of disease that is progressing, should we go ahead and give them some palliation in terms of symptoms in the short term.   The most common subtype of advanced breast cancer that we treat is hormone receptor positive, HER2 negative breast cancer. There are data that have been previously presented that show that fulvestrant, which is an injectable selective estrogen receptor downgrader, is possibly superior to aromatase inhibitors. So one trial evaluated this concept, but in the face of CDK4/6 inhibition. CDK4/6 inhibitors have become the mainstay of therapy in advanced hormone receptor positive, HER2 negative breast cancer. What abstract 1007, or the PARSIFAL trial, looked at was is fulvestrant and a CDK4/6 inhibitor superior to an aromatase inhibitor and CDK4/6 inhibitor. And what they showed is that, in advanced breast cancer, fulvestrant was not superior to an aromatase inhibitor when given in combination with CDK4/6 inhibition. And this is something that I think was reassuring to patients, especially if they have to come in to the clinic to receive an injection.   What will be interesting going forward is how do selective estrogen receptor downgraders that are oral come into play, and how do they compare with fulvestrant or how do they compare with aromatase inhibitors. So that was something that was quite reassuring, that we can give aromatase inhibitors with CDK4/6 inhibitors without compromising efficacy in patients with advanced breast cancer.   Another trial that generated some excitement for our patients and therapeutic options is the BYLieve trial, or abstract 1006. As I stated earlier, the mainstay of therapy for those patients with advanced breast cancer that's hormone receptor positive and HER2 negative is some type of endocrine partner, whether it be tamoxifen, fulvestrant, or an aromatase inhibitor and a CDK4/6 inhibitor. Mainly, it's an aromatase inhibitor and a CDK4/6 inhibitor. So for those patients that progress on that regimen, what do we do next is something that comes up.   We know that up to 40% of patients with advanced breast cancer that's hormone receptor positive and HER2 negative have PI3-kinase mutations, and alpha-specific PI3-kinase inhibitor that has shown to improve outcomes in patients with advanced breast cancer that have PI3-kinase mutations. What the BYLieve trial looked at was how about after CDK4/6 inhibition.   And what it showed is that patients that received CDK4/6 inhibition and fulvestrant and alpelisib did have about a 50% chance of not progressing at six months. And there was about a seven-month progression-free survival benefit in these patients. The toxicities that we know of with alpelisib include rash, diarrhea, and hypoglycemia. And those side effects were reported less than in the SOLAR-1 trial.   So we know that, in this group of patients, we really do need to monitor their blood sugars, give them prophylactic antihistamines, and also counsel them on adequate anti-diarrheal management. So the BYLieve trial helped us with two concepts. One is, after CDK4/6 inhibition, in those patients with PI3-kinase mutations, yes, there is a role for alpelisib. And the second thing is that we're doing a better job, while we can't do cross-trial comparisons, of improving the quality of life and symptoms that arise from alpelisib, including the rash, the diarrhea, and the hypoglycemia.   Another trial that was very exciting, shifting gears, is the HER2CLIMB trial. And that was abstract 1005. We knew from December that tucatinib improves outcomes when added to trastuzumab and capecitabine in patients with advanced HER2 positive breast cancer. We also knew that it does improve survival irrespective of brain metastases, and brain metastases that might have been progressing.   What this analysis of the HER2CLIMB showed was that the patients that received tucatinib did have an improved survival benefit compared with trastuzumab and capecitabine of six months. Additionally, the response rate solely in the central nervous system was 41% on the tucatinib arm versus 23% on the arm that received capecitabine and trastuzumab alone. So these were really exciting data because we do know that about 50% of patients with advanced stage IV breast cancer that's HER2 positive do eventually develop brain metastases.   So while we know that tucatinib, in addition to trastuzumab and capecitabine, does improve survival irrespective of brain metastases, we know now that those patients with progressing brain metastases do have an improved outcome when tucatinib is added. The side effects that we have to monitor for are diarrhea and liver function abnormalities, of course.   Shifting gears a little bit more is the immunotherapy trial in triple-negative breast cancer. And that is abstract 1000. So over the past 12 to 18 months, we've seen data from the IMpassion130 trial, which showed that patients who had PD-L1 positivity in their immune cells did derive benefit when atezolizumab was added to nab-paclitaxel, and it did improve outcomes.   Now, this trial, the KEYNOTE-355 trial, looked at patients that were untreated for their advanced breast cancer. And these patients were randomized to paclitaxel, nab-paclitaxel, or gemcitabine and carboplatin chemotherapy with pembrolizumab or without pembrolizumab. And what was noted is those patients that had a combined positive score of PD-L1 greater than or equal to 10 derived about a four-month progression-free survival benefit if they received pembrolizumab.   Now, we have two trials, the IMpassion trial and the KEYNOTE trial, that show that patients with some element of PD-L1 expression, whether it's the immune cells, as evidenced by the IMpassion trial, or the combined positive score of PD-L1, as was evaluated in the KEYNOTE trial, did have significantly better outcomes if immunotherapy was incorporated as first-line treatment for their triple-negative breast cancer.   There are questions, though, that we have to answer, in what is the optimal measurement to predict response to immunotherapy in the triple-negative breast cancer setting, and also what is the optimal cut point that we should use to say whether we should employ immunotherapy. However, it was another advancement for an unmet need, which is triple-negative breast cancer.   One thing we know in advanced breast cancer, whether it's because of PI3-kinase mutations, whether it's measuring PD-L1, that we need to do testing beyond estrogen receptor, progesterone receptor, and HER2. We're increasingly utilizing genomic and germline testing to see if we can give more personalized therapy to our patients. 1002 looked at the effectiveness of patients with BRCA mutations that were somatic, as well as patients with germline mutations, including PALB2, and they found that olaparib did improve outcomes in patients with somatic BRCA mutations, as well as those patients that harbored PALB2 mutations. So I think that this is another reason for us to make sure that we are sending our patients for germline testing in the advanced breast cancer setting, as well as to make sure that we're looking for somatic mutations that we can target.   ASCO Daily News: What are your key takeaways from the studies on early breast cancer?   Dr. Neelima Denduluri: Thanks for asking that question. As I said earlier, there are many advancements, but one that I want to highlight is abstract 501. We know that anthracyclines have improved survival in breast cancer over the last several decades. However, we also know that HER2-targeted therapy using trastuzumab, pertuzumab, and now TDM1 has significantly improved outcomes in early breast cancer. So we've never known whether we truly need to give anthracyclines in the face of effective HER2-targeted therapy.   The TRAIN-2 trial, which is abstract 501, evaluated whether anthracyclines improve outcomes when there is optimal HER2-targeted therapy. And the answer is no, it did not. So I think that's very promising. And potentially, what we'll be able to do is to decrease cardiotoxicity, as well as treatment-related leukemias and myelodysplasia, possibly, in terms of reducing the risk of those by omitting anthracyclines in the early HER2 breast cancer setting.   Another abstract that I want to highlight is 507, which was looking at the role of adjuvant capecitabine in a metronomic fashion, meaning lower doses and giving it for a longer period of time, in those patients with triple-negative breast cancer. Just to give a quick historical background, we know from the CREATE-X trial that those patients that received preoperative therapy with third-generation chemotherapy and had residual disease at the time of surgery, those patients did benefit from the addition of capecitabine as part of their adjuvant treatment, compared with no adjuvant treatment.   So these are further data that we have further elucidating the role of capecitabine, primarily in the triple-negative breast cancer setting. And we did see that there was an improved outcome in terms of disease-free survival in these patients with anatomic stage I to III triple-negative breast cancer, and they did benefit from the addition of capecitabine.   Also, two side effects that we worry about with capecitabine are diarrhea and hand-foot syndrome. And they seem to be more manageable with this lower dose of capecitabine compared with the traditional 2,500 mgs per meter squared twice a day that was approved initially with capecitabine or that was used in CREATE-X.   ASCO Daily News: Dr. Denduluri, are there any new advancements in supportive care and symptom management?   Dr. Neelima Denduluri: So Geraldine, we know that a geriatric assessment is very important when we treat our patients that are elderly. Abstract 12009 performed a geriatric assessment on patients that had stage III or IV cancer and were aged 70 or older. And once they performed that geriatric assessment, they sent the treating oncologist the geriatric assessment and guided recommendations to improve their tolerance to therapy, potentially. And what they found is that it reduced clinically graded grade III to V toxicities significantly by providing this geriatric assessment. And also, it didn't lower survival.   So I thought that this was really nice prospective data that shows that we should be performing a geriatric assessment, and what we find, we should make sure to support our patients better based on the findings. And this improves our patients' tolerability to therapy, and it does not decrease their survival. So I thought that that was a very uplifting trial. We have a lot of programs around the country that are saying how best do we support our geriatric population, and this was a good step in the right direction.   ASCO Daily News: Absolutely. Is there anything else you'd like to add today? Any other abstracts that we should know about?   Dr. Neelima Denduluri: A couple of other things that we talk about quite a bit in our clinic is disparities. And abstract 1080 found that those patients with triple-negative breast cancer were continuing to receive non-guideline-adherent care when it was compared to their Caucasian population compared with the black population. So I think that this underscores that we really need to make sure that we address the disparities in cancer care.   Cancer survivorship is very important. One thing that patients complain about is insomnia. Abstract 12005 showed that yoga, cognitive behavioral therapy, and survivorship health education really improved insomnia in cancer survivors. So again, when we look at taking care of patients, we really need to look at the whole spectrum. And while we have excellent drugs and drug development that is improving outcomes, we also need to make sure that disparities, financial toxicity, survivorship are addressed. And therefore, I thought that this ASCO did a great job of looking at those issues, as well as drug development.   ASCO Daily News: Absolutely. Well, thank you, Dr. Denduluri, for sharing your insights with us today on these promising new developments in the breast cancer field.   Dr. Neelima Denduluri: Thank you, Geraldine.   ASCO Daily News: And thanks to our listeners for joining us today. If you're enjoying the content on the podcast, please take a moment to rate and review us on Apple 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. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

In this episode, we speak with Rahul Saxena, Associate Director of CREATE-X. CREATE-X is a faculty-led, student-focused initiative to instill entrepreneurial confidence in Georgia Tech’s students. It provides students the knowledge, skills, abilities, and experiences to confidently pursue entrepreneurial opportunities.

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In collaboration with Startup Exchange, Georgia Tech's Student Entrepreneur Community, this recorded fireside chat is with Chris Klaus: Georgia Tech Alumni, Serial Entrepreneur, and Co-Founder of CyberLaunch VC, NeuroLaunch and and Kaneva. But he is most known for being the Founder/CEO of Internet Security Systems which was acquired by IBM. He has also had a long relationship with Georgia Tech and invigorates the future of technology at Georgia Tech by supporting CREATE-X.

Create x Hustle x Repeat - PODCAST w/ BOOGIEVISION x Terrell "MOCCA" King - "You Are The Brand" #109 by BOOGIEVISION

Create x Hustle x Repeat - PODCAST w/ BOOGIEVISION x Storyboard T | "Fighting Writers Block" #108 by BOOGIEVISION

Create x Hustle x Repeat w Boogievision x Lyndon McCray | EPISODE # 107 Like by BOOGIEVISION

Create x Hustle x Repeat w Boogievision x Larry "Legend" Spivey | EPISODE # 106 Like by BOOGIEVISION

Create x Hustle x Repeat - w/ BOOGIEVISION x Hala Maroc EPISODE #105 by BOOGIEVISION

What's the Buzz is back for Spring 2017! Today, host Jasmine Pillarisetti talks with Charles Lankau, a BME student who participated in last summer's CREATE-X course (aka Startup Summer). Listen to learn more about his team's product, what the experience was like, and how they achieved success (including how they won the demo competition!).  If you are interested in pursuing your own startup, the application deadline for this summer's Startup Launch is March 17! Apply here: http://startupsummer.gatech.edu/apply/  And as always, if you are interested in making your own podcasts for the BME Learning Commons, contact Jasmine at jasminepill@gatech.edu! 

Dr Toi talks to ecancertv at SABCS 2015 about the results of the CREATE-X phase III clinical trial that have shown that capecitabine improves survival outcomes in women with HER2-negative breast cancer who have invasive disease after neoadjuvant chemotherapy. In the interview, Dr Toi explains that women who do not achieve a pathological complete response (pCR) after neoadjuvant chemotherapy with an anthracycline and a taxane have an intermediate or high-risk for relapse. The CREATE-X trial was designed to see if further systemic chemotherapy with capecitabine would be beneficial for these patients. Dr Toi and colleagues have previously reported data to show that adding capecitabine to standard adjuvant radiotherapy or hormone therapy was feasible and well tolerated. The findings presented at SABCS 2015 showed that the addition also improved the primary endpoint of 2-year disease-free survival by about 32% (87.3% vs 80.5%, p=0.001) and the secondary endpoint of overall survival (96.2% vs 93.9%, p=0.086) by about 35% versus standard adjuvant therapy alone. Tolerability was consistent with the established safety profile of capecitabine in metastatic breast cancer and the results suggest there may be a role for capecitabine in some women after neoadjuvant chemotherapy.

Dr Toi talks to ecancertv at SABCS 2015 about the results of the CREATE-X phase III clinical trial that have shown that capecitabine improves survival outcomes in women with HER2-negative breast cancer who have invasive disease after neoadjuvant chemotherapy. In the interview, Dr Toi explains that women who do not achieve a pathological complete response (pCR) after neoadjuvant chemotherapy with an anthracycline and a taxane have an intermediate or high-risk for relapse. The CREATE-X trial was designed to see if further systemic chemotherapy with capecitabine would be beneficial for these patients. Dr Toi and colleagues have previously reported data to show that adding capecitabine to standard adjuvant radiotherapy or hormone therapy was feasible and well tolerated. The findings presented at SABCS 2015 showed that the addition also improved the primary endpoint of 2-year disease-free survival by about 32% (87.3% vs 80.5%, p=0.001) and the secondary endpoint of overall survival (96.2% vs 93.9%, p=0.086) by about 35% versus standard adjuvant therapy alone. Tolerability was consistent with the established safety profile of capecitabine in metastatic breast cancer and the results suggest there may be a role for capecitabine in some women after neoadjuvant chemotherapy.

A critical review on the practice changing studies presented at the San Antonio Breast Cancer Symposium, held December 2015, is presented in this podcast. A number of areas, including neoadjuvant and adjuvant treatment, treatment of metastatic disease and the emergence of new biomarkers are addressed. Trials discussed include the WSG-ADAPT HER2+/HR+ phase II trial, which assessed 12-weeks of neoadjuvant TDM1 with or without endocrine therapy vs. trastuzumab+endocrine therapy in HER2-positive hormone-receptor-positive early breast cancer, the CREATE-X study, which assessed adjuvant capecitabine in patients with HER2-negative pathologic residual invasive disease after neoadjuvant chemotherapy, and the TH3RESA study, which investigated trastuzumab emtansine use in patients with previously treated HER2-positive metastatic breast cancer. Further, studies on new promising biomarkers such as the prognostic value of circulating tumor cells in follow up of early breast cancer patients after adjuvant chemotherapy are highlighted. Overall, the present podcast represents a comprehensive overview on some of the most important studies presented at the San Antonio Breast Cancer Symposium. These highlights are presented by Jacek Jassem, Department of Oncology and Radiotherapy, Medical University of Gdansk, Poland (jjassem@gumed.edu.pl). The podcast is conducted by Anna Berghoff, Department of Medicine, Medical University of Vienna, Austria. Visit the ESMO Open website: http://esmoopen.bmj.com/content/1/1/e000043.