Podcasts about Oncology

In this episode, we review the high-yield topic of Microtubule Inhibitors from the Oncology section. Follow Medbullets on social media: Facebook: www.facebook.com/medbullets Instagram: www.instagram.com/medbulletsofficial Twitter: www.twitter.com/medbulletsIn this episode --- Send in a voice message: https://anchor.fm/medbulletsstep1/message

This month, we reviewed key topics and interviews from the American Society of Clinical Oncology 2022 Annual Meeting.

The Federal Trade Commission unanimously launched a formal inquiry into the business practices of the prescription drug middleman industry—known as pharmacy benefit managers (PBMs)—in early June 2022 due to the overwhelming response of more than 24,000 public comments during their request for information. Listen to ACCC's Matt Devino and Dr. Rahul Seth discuss why every voice is critical in grassroots advocacy efforts on both the federal and state level, and how cancer professionals who moonlight as patient advocates can help improve access to care and reduce financial toxicity for people living with cancer. Speakers Matt Devino, MPH Director, Cancer Care Delivery & Health Policy Association of Community Cancer Centers Rahul Seth, DO Assistant Professor of Medicine State University of New York Upstate Medical University Related Resources State by State: Advocacy Advances PBM Reform, Part 1 State by State: Advocacy Advances PBM Reform, Part 2 FTC Requests Public Comments on the Impact of Pharmacy Benefit Managers' Practices FTC Launches Inquiry Into Prescription Drug Middlemen Industry Oncology State Societies Advocacy Engagement Pilot ACCC Legislative Action Center

In this episode, we review the high-yield topic of Paraneoplastic Effects of Tumors from the Oncology section. Follow Medbullets on social media: Facebook: www.facebook.com/medbullets Instagram: www.instagram.com/medbulletsofficial Twitter: www.twitter.com/medbulletsIn this episode --- Send in a voice message: https://anchor.fm/medbulletsstep1/message

“My White Coat Doesn't Fit” by Narjust Florez (Duma): a medical oncologist shares her story about exclusion, depression and finding her way in oncology as a Latina in medicine and oncology.   TRANSCRIPT Narrator: My White Coat Doesn't Fit, by Narjust Duma, MD (10.1200/JCO.21.02601) There I was, crying once again all the way from the hospital's parking lot to my apartment, into the shower, and while trying to fall asleep. This had become the norm during my internal medicine residency. For years, I tried hard every day to be someone else in order to fit in. It started with off-hand comments like “Look at her red shoes,” “You are so colorful,” and “You are so Latina.” These later escalated to being interrupted during presentations with comments about my accent, being told that my medical school training in my home country was inferior to my US colleagues, and being assigned all Spanish-speaking patients because “They are your people.” Some of those comments and interactions were unintentionally harmful but led to feelings of isolation, and over time, I began to feel like an outsider. I came to the United States with the dream of becoming a physician investigator, leaving behind family, friends, and everything I knew. Over time, I felt pigeonholed into a constricting stereotype due to my ethnicity and accent. Back home, I was one of many, but in this new setting, I was one of a few, and in many instances, I was the only Latina in the room. I was raised by divorced physician parents in Venezuela; my childhood years were often spent in the clinic waiting for my mother to see that one last patient or outside the operating room waiting for my father to take me home. The hospital felt like my second home, growing up snacking on Graham crackers and drinking the infamous hospital's 1% orange juice. “She was raised in a hospital,” my mother used to say. Sadly, that feeling of being at home in the hospital changed during medical training as I felt isolated and like I did not belong, making me question my dream and the decision to come to the United States. I remember calling my family and crying as I asked “Why did I leave?” “Why didn't you stop me from coming here?” and seeking permission to return home. I felt like I was disappointing them as I was no longer the vivid, confident young woman who left her home country to pursue a bright future. I remember one colleague, Valerie (pseudonym), from Connecticut. Valerie attended medical school in the United States, did not have an accent, and was familiar with the American health care system. She understood how the senior resident-intern relationship functioned, a hierarchy that continually confused me. Over the following weeks, I took a closer look at how my colleagues and other hospital staff interacted with Valerie. I noticed that people did not comment about her clothing or personality. She was “normal” and fit in. I remember my senior resident asking me, “Narjust, why can't you be more like Valerie?” Ashamed, I mumbled that I would try and then ran to the bathroom to cry alone. That interaction was a turning point for me; I got the message. I needed to change; I needed to stop being who I was to be accepted. As the years passed, I kept key pieces of my personality hidden, hoping I could earn the respect of my colleagues. I refrained from sharing my personal stories as they were different from those around me. I grew up in a developing country with a struggling economy and an even more challenging political situation. It was clear that we simply did not share similar experiences. When I sought help from my senior residents and attending physicians, my feelings were often minimized or invalidated. I was told that “residency is tough” and that I should “man up.” A few even suggested that I mold my personality to fit the box of what a resident physician was supposed to be. I slowly realized that my clothing changed from reds and pinks to greys and blacks because it was “more professional”; my outward appearance faded, as did my once bright sense of humor and affability. All these issues led to depression and an overwhelming sense of not belonging. A few months later, I was on antidepressants, but the crying in the shower continued. Rotation by rotation, I looked for a specialty that would help me feel like I belonged, and I found that in oncology. My mentor embraced my research ideas; my ethnic background or accent did not matter; we had the same goal, improving the care of our patients with cancer. I got to travel to national and international conferences, presented my research findings, and received a few awards along the way. From the outside, it looked like I was thriving; my mentor often called me a “Rising Star,” but in reality, I was still deeply depressed and trying to fit in every day. My career successes led me to believe that not being myself was the right thing to do. I felt isolated; I was trying to be someone I was not. A year later, I matched at my top choice oncology fellowship program; the program had the balance I was looking for between clinical care and research. This meant that I needed to move to the Midwest, further away from family, and to an area of the country with less racial and ethnic diversity. After 2 years on antidepressants and the 10 extra pounds that came with it, my white coat did not fit. My white coat felt like a costume that I would put on every day to fulfill the dream of being a doctor. I would often wake up in the middle of the night exhausted and depressed. I had all the responsibilities of a hematology/ oncology trainee and the additional full-time job of trying to fit in every day; I was using all my energy trying to be someone I was not. Regardless of my fears, I felt in my element when talking to patients and interacting with my cofellows. Despite having a different skin color and accent, I felt accepted by my patients with cancer. I remember when one of my patients requested to see me while in the emergency room because “Dr Duma just gets me.” She had been evaluated by the head of the department and attending physicians, but for her, I washer doctor. Tears of happiness accompanied my bus ride to see her; at that moment, I knew I was an oncologist, and oncology was the place I belonged. The next day, I realized that it was time to be myself: Narjust from Venezuela, a Latina oncologist who was her true self. I searched the bottom of my closet for the last piece of colorful clothing I had saved, a yellow dress. I put on that brightly colored dress for the first time in 5 years and finally felt comfortable being my authentic self; the yellow dress represented freedom and embraced the culture and colors I grew up seeing in my hometown. I finally understood that I brought something special to the table: my unique understanding of the challenges faced by Latinx patients and trainees, my advocacy skills, and my persistence to endure the academic grindstone. Psychotherapy was also an essential part of my recovery; I learned that happiness lived within me as a whole person—hiding my accent, cultural background, and past experiences was also hiding the light and joy inside me. Along the way, I found colleagues who faced the same challenges and validated that my experiences resulted from an environment that excludes the difference and values homogeneity. This route to self-discovery helped me find my calling to support others in situations similar to mine.3 I learned how to incorporate and celebrate my ethnicity in the world of academic oncology by teaching others the power of cultural humility, diversity, equity, and inclusion. Together with newfound friends and colleagues, I cofounded the #LatinasinMedicine Twitter community for those who face similar burdens during their training and careers. The #LatinasinMedicine community was created to share our stories, embrace our culture, and amplify other Latinas in medicine—to create connections that alleviate the sense of isolation that many of us have experienced and serve as role models to the next generation of Latinas in medicine. To help drive systemic change, I founded the Duma Laboratory, a research group that focuses on cancer health disparities and discrimination in medical education. Through research, the Duma Laboratory has shown that my experiences are not unique but rather an everyday reality for many international medical graduates and other under-represented groups in medicine. The Duma Laboratory has become a safe environment for many trainees; we seek to change how mentorship works for under-represented groups in oncology, with the hope that the isolation I felt during my training is not something that future physicians will ever have to endure. After years of depression and self-discovery, my white coat now fits. However, this is not your regular white coat; it has touches of color to embrace my heritage and the ancestors who paved the way for me to be here today. The face of medicine and oncology is changing around the world; young women of color are standing up to demonstrate the strength of our experiences and fuel the change that medical education needs. For all minority medical students, residents, fellows, and junior faculty, we belong in medicine even during those moments when our identity is tested. Through my journey, I learned that we can and must challenge the status quo. I hope to inspire others to join me in this path of advocating for diversity, equity, and inclusion because the time for change is now. I was finally free the moment I realized I could not be anyone else but myself, a proud Latina in medicine and oncology. Dr. Lidia Schapira: Welcome to JCO's Cancer Stories: The Art of Oncology, brought to you by the ASCO Podcast Network, which offers a range of educational and scientific content and enriching insight into the world of cancer care. You can find all of the shows including this one at podcast.asco.org. I'm your host, Lidia Shapira, Associate Editor for Art of Oncology and Professor of Medicine at Stanford. And with me today is Dr. Narjust Duma, Associate Director of the Cancer Care Equity Program and Medical Thoracic Oncologist at Dana Farber and an Assistant Professor at Harvard Medical School. We'll be discussing her Art of Oncology article, ‘My White Coat Doesn't Fit.' Our guest has a consulting or advisory role with AstraZeneca, Pfizer, NeoGenomics Laboratories, Janssen, Bristol Myers Squibb, Medarax, Merck, and Mirati. Our guest has also participated in a speaker's bureau for MJH Life Sciences. Narjust, welcome to our podcast. Dr. Narjust Duma: Thank you for the invitation and for letting us share our story. Dr. Lidia Schapira: It's lovely to have you. So, let's start with a bit of background. Your essay has so many powerful themes, the story of an immigrant in the US, the story of resilience, the story of aggression and bullying as a recipient of such during training, of overcoming this and finding not only meaning, but really being an advocate for a more inclusive and fair culture in the workplace. So, let's untangle all of these and start with your family. I was interested in reading that you're named after your two grandmothers, Narcisa and Justa. And this is how your parents, both physicians, Colombian and Dominican, gave you your name, and then you were raised in Venezuela. So, tell us a little bit about your family and the values that were passed on in your family. Dr. Narjust Duma: Thank you for asking. Having my two grandmothers names is something that my mother put a lot of effort into. She was a surgery resident with very limited time to decide to do that. And I don't have a middle name, which is quite unique in Latin America, most people in Latin America have one or two middle names. So, my mother did that to assure that I will use her piece of art, which is my first name. But little does she know that my grandmothers were going to be such an important part of my life, not only because they're in my name, but also because I am who I am thanks to them. So, the first part of my name, Narcisa was my grandma who raised me and she gave me the superpower of reading and disconnecting. So, I'm able to read no matter where I am and how loud it can be and disconnect with the world. So, it is often that my assistants need to knock on my door two or three times so, I don't like being scared because I'm able to travel away. That was also very unique because you will find me in the basketball games from high school or other activities with a book because I was able to block that noise. But it also makes very uncomfortable situations for my friends that find it embarrassing that I will pull a book in the basketball game. And as I grow, thanks to the influence of my grandmothers, I always have these, how can I say, mixed situation, in which they were very old school grandmothers with old school habits and values, and how I'm able to modify that. My grandma told me that you can be a feminist, but you still take care of your house. You can still, you know, cook. And that taught me that you don't have to pick a side, there is no one stereotype for one or another. Because as my mother being a single mother and a surgeon, my parents divorced early on, told me, ‘Yes, I can be the doctor but I can also be the person that has more than a career that's able to have hobbies.' I love cooking, and when I'm stressed, I cook. So, I had a grant deadline a few weeks ago and I cooked so much that there was food for days. So, having the names of my grandmothers is very important because I have their values, but I have modified them to the current times. Dr. Lidia Schapira: Let me ask a little bit about reading. I often ask the guests of this podcast who have written and therefore I know enjoy reading and writing, what their favorite books are or what is currently on their night table. But I'm going to ask you a second question and that is what languages do you read in? Dr. Narjust Duma: I prefer to read in Spanish. I found that books in Spanish, even if it's a book that originated in English, have these romantic characteristics. And I often tell my editors, ‘Just take into account that I think in Spanish, and write in English'. Because I grew up with Gabrielle Garcia Marquez, and when he describes a street, that's a page of the little things that he describes. So, that's how I write and that's how I read in a very romantic, elaborate way. The aspects of realistic imagism, which is my favorite genre in literature, and there are so many Latin American and South American writers that I don't think that I am going to run out. And when I run out, I reread the same books. I have read all of Gabrielle Garcia Marquez's books twice, and Borges, too. It's the type of stories that allows you to submerge yourself and you imagine yourself wearing those Victorian dresses in the heat of a Colombian street, as you try to understand if, you know, Love in the Time of Cholera, if they were more in love with being in love or what it was happening in the story. And that just gives me happiness on a Sunday morning. Dr. Lidia Schapira: That's beautiful. I must confess that reading Borges is not easy. So, I totally admire the fact that you have managed to read all of his work. And I think that you're absolutely right, that magical realism is a genre that is incredibly fresh, and perhaps for the work that we do in oncology, it's a wonderful antidote in a way to some of the realities, the very harsh realities that we deal with on a daily basis. So, let me ask you a little bit about growing up in Venezuela in the 80s, 90s, early aughts. That must have been difficult. Tell us a little bit about that, and your choice of attending medical school. Dr. Narjust Duma: So, growing up in Venezuela, with a Colombian mother, it was quite a unique perspective because she was very attached to her Colombian roots. So, a lot of the things that happened in the house were very Colombian, but I was in Venezuela. So, it was a unique characteristic of being from a country but your family is not from there. So, my parents are not from Venezuela, my grandparents either, and I'm Venezuelan because I was born and raised there. So, that brought a unique perspective, right? The music that I played in my house was Colombian music, not Venezuelan music. So, my family migrated from Colombia to Venezuela due to the challenges in the early 80s with violence and the Medellin, due to the drug cartels. So, we moved to Venezuela for a better future. And growing up in the first years, Venezuela was in a very good position. Oil was at the highest prices. Economically, the country was doing well. I remember, in my early years, the dollar and the bolivar had the same price. But then little by little I saw how my country deteriorated, and it was very heartbreaking. From a place where the shells were full of food to a place now when there is no food, and you go to the supermarket, and many of them are close. And now you're only limited to buying certain things. And you used to use your federal ID that has an electronic tracking on how much you can buy because of socialism. So, you're only allowed to buy two kilograms of rice per month, for example, you're only allowed to buy this number of plantains. So, every time I go home, because Venezuela is always going to be my home, it doesn't matter where I am., I see how my country has lost pieces by pieces, which is quite very hard because I had a very good childhood. I had a unique childhood because I was raised in hospitals. But I had a childhood in which I will play with my friends across the street. We were not worried about being kidnapped. We were not worried about being robbed. That's one thing that children in Venezuela cannot do right now. Children of doctors – there's a higher risk of being kidnapped as a kid right now if your father is a doctor or your mother. So, my childhood wasn't like that. When I teach my students or talk to my mentees, I'm often selling my country, and saying that's not what it used to be. That's not where I grew up. But every year I saw how it no longer is where I grew up. That place doesn't exist, and sometimes, Lidia, I feel like my imagination may have to fill it out with more good things. But I think it was a good childhood. It's just that nobody in Venezuela is experiencing what I experienced as a kid. Dr. Lidia Schapira: So, both parents were doctors and you chose to study medicine, was this just right out of high school? Dr. Narjust Duma: Even before high school, I found myself very connected to patients. So, since I turned 15, my father would give his secretary a month of vacation because that's the month that we fill in. So, I was the secretary for a month every summer since I was 15 until I was 20. That early exposure allowed me to like get to know these patients and they know I was the daughter, but I was also the secretary. So, I really cherished that. Growing up in my household, we're a house of service. So, our love language is acts of service. That's how pretty much my grandmas and my parents were. So, in order to be a physician, that's the ultimate act of service. I have wanted to be a doctor since I was 11. I think my mother face horrible gender harassment and sexual harassment as a female in the surgery in the early 80s, that she tried to push me away from medicine. Early on, when I was 11, or 12, being an oil engineer in Venezuela was the career that everybody should have, right? Like, people were going to the Emirates and moving to different parts of the world and were doing wonderful. So, my mother, based on her experience in the 80s, was pushing me away from it. She's like, ‘You can do other things.' My father always stayed in the back and said, ‘You can do what you want.' This is how our parents' experiences affect our future. If I wouldn't be this stubborn, I would probably be an oil engineer today, and I wouldn't be talking to you. Dr. Lidia Schapira: So, you went to medical school, and then after you graduated, what did you decide to do? Because when I look at what we know about the history there is I think you graduated in '09, and then the story that you write about sort of begins in '16 when you come to New Jersey to do training in the US, but what happened between '09 and '16? Dr. Narjust Duma: I started residency in 2013. '16 was my fellowship. So, going to medical school was one of the hardest decisions I made because right in 2003 and 2004 was a coup in Venezuela where part of the opposition took over the country for three days, and then the President of the time came back and the country really significantly destabilized after that coup. Most schools were closed. Entire private industries were closed for a month. And I think for some people, it's hard to understand what happened. Everything closed for a month, McDonald's was closed for a month. There was no Coke because a Coke company was not producing. Everything was closed. The country was just paralyzed. So, my mother and I, and my family, my father, took into account that we didn't know when medical school would resume in Venezuela. We didn't know if the schools would ever open again. I decided to apply for a scholarship and I left Venezuela at the age of 17 to go to the Dominican Republic for medical school. Very early on, I noticed that I was going to be a foreigner wherever I go because I left home. And since then, I think I became very resilient because I was 17 and I needed to move forward. So, that is what happened in 2004. I left everything I knew. I left for the Dominican. I do have family in the Dominican, but it was very hard because even if you speak the same language, the cultures are very different. And then I went to medical school in the Dominican and when I was in the Dominican Republic, I realized I really wanted to do science and be an advocate and focus on vulnerable populations with cancer. So, then I made the decision to come to the United States, I did a year of a research fellowship at Fred Hutchinson, and then I went to residency in 2013. Dr. Lidia Schapira: I see. And that's when you went to New Jersey, far away from home. And as you tell the story, the experience was awful, in part because of the unkindness and aggression, not only microaggression but outright bullying that you experienced. In reading the essay, my impression was that the bullying was mostly on two accounts. One was gender. The other was the fact that you were different. In this particular case, it was the ethnicity as a Latin or Hispanic woman. Tell us a little bit about that so we can understand that. Dr. Narjust Duma: I think what happened is that perfect example of intersectionality because we are now the result of one experience, we're the result of multiple identities. So many woman have faced gender inequalities in medicine, but when you are from a marginalized group, those inequalities multiply. I have an accent and clearly a different skin color. I grew up in a family in which you were encouraged to be your true self. My grandmothers and my mother said, ‘You never want to be the quiet woman in the corner because the quiet woman never generates change.' That's what they said, and I bet there are some who do. But that intersection of my identities was very challenging because I was seen as inferior just for being a woman and then you multiply being one of the few Latinas you are seen like you are less just because you are - it doesn't matter how many degrees or papers or grants you had done and all, I was the most productive research resident in my residency for two years in a row - but I would still be judged by my identity and not what I have produced, or what I do on my patients' experiences, which were great – the feedback from my patients. It's just because I was the different one. Dr. Lidia Schapira: When I hear your story about your origins, it seems to me that you came from a very capable loving family, and they basically told you to go conquer the world, and you did. And then you arrive and you're a productive successful resident, and yet, you are marginalized, as you say. People are really aggressive. Now that you've had some years that have passed, if you think back, what advice would you give that young Narjust? Dr. Narjust Duma: My number one advice, would be that, I will tell myself is that I belong, in many instances, I feel like I didn't belong. It makes me question all the decisions to that day because when you're doing a presentation, and I still remember like today, and you're interrupted by someone, just for them to make a comment about your accent, it really brings everything down to your core, like, 'Is my presentation not accurate? Is the information not all right? And why am I here? Why did I left everything I love to be treated like this?' Dr. Lidia Schapira: Of course. So, from New Jersey, you write in your essay that you really discover your passion for cancer research, and you land in a fellowship with a mentor who is encouraging, and things begin to change for you. Can you tell us a little bit about that phase of your training in your life where you slowly begin to find your voice in the state, that also where you crash, where you find yourself so vulnerable that things really fall apart? Dr. Narjust Duma: So, when I was a resident, I didn't know exactly - I was interested in oncology, but I wasn't sure if it was for me. So, Dr. Martin Gutierrez at Rutgers in Hackensack is the person who I cold emailed and said, ‘I'm interested in studying gastric cancer in Hispanic patients because I think that patients in the clinic are so young.' He, without knowing me or having any idea, he trusted me. We still meet. He still follows up with me. He encouraged me. I think him being a Latino made the experience better, too, because I didn't have to explain my experience to him. I didn't have to explain that. He understood because he went through the same things. And he's like, ‘I got you. Let's follow what you want to do.' He embraced who I was, and how I put who I was into my research. And thanks to Dr. Gutierrez, I'm at the Mayo Clinic as an international medical grad. So, finding a place in which my ideas were embraced was very important to allow me to stay in medicine because, Lidia, I can tell you several times, I decided to leave. I was very committed to finding something else to do or just being a researcher and leaving clinical medicine behind. So, when I went to Mayo, I still followed with that mentor, but I already knew what I wanted to do. I wanted to do cancer health disparities. I wanted to do inclusion and diversity. And that allowed me to develop the career I have now and is having that pathway because I, with my strong personality and everything else, faced this discrimination, and I can imagine for other trainees that may still be facing that or will face that in the future. So, I use the negative aspects to find my calling and do many things I have done after that. Dr. Lidia Schapira: Speaks to your strengths and your determination. Let's talk a little bit about the people who may also feel different but whose differences may not be so apparent. How do you now as an emerging leader, and as a mentor, make sure that you create an inclusive and safe environment for your younger colleagues and your mentees? Dr. Narjust Duma: One of the things that resulted was the founding of the Duma Lab, which is a research group that focuses on cancer, health disparities, social justice as a general, and inclusion in medical education. So, one of the things that I practice every day is cultural humility. I continue to read and remember the principles. I have them as the background on my computer at work. The number one principle in lifelong learning is that we learn from everyone and that we don't know everything and other people's cultures, and subculture, we learn their culture is rich. So, in every meeting, I remind the team of the principles of cultural humility when somebody is joining the lab. I have one-on-one meetings, and I provide information and videos about cultural humility because the lab has been created as an environment that's safe. We have a WhatsApp group that is now kind of famous - it's called The Daily Serotonin. The majority of the members of the lab are part of marginalized groups, not only by gender but race, religion, sexual and gender orientation. So, we created this group to share good and bads, and we provide support. So, a few weeks ago, a patient made reference to one of their lab member's body, the patient was being examined and that was quite inappropriate. The member debriefed with the group and we all provided insights on how she had responded, and how she should respond in the future. That's not only learning from the person that brought the scenario but anybody else feels empowered to stop those microaggressions and stop those inappropriate behaviors that woman particularly face during clinical care. So, cultural humility, and having this WhatsApp group that provides a place where, first, I remind everybody that's confidential, and a place in which anything is shared has been very successful to create inclusivity in the group. Dr. Lidia Schapira: You have such energy and I'm amazed by all of the things that you can do and how you have used social connection as a way of bringing people up. So, can you give our listeners perhaps some tips for how you view creating a flatter culture, one with fewer hierarchies that makes it safer for learners and for those who are practicing oncology? What are three quick things that all of us can do in our work starting this afternoon? Dr. Narjust Duma: The concept is that we all can be allies. And being an ally doesn't take a lot of time or money because people think that being an ally is a full-time job, it is not. So, the first one tip will be to bring people with you. Your success is not only yours. It's a success of your mentees. It's a success of your colleagues. So, don't see your success as my badge on my shoulder. It's the badge that goes on everyone. So, bring people in, leave the door open, not only bring them but leave the door open because when you do it helps the next generation. Two, little things make a difference. I'm going to give you three phrases that I use all the time. When you think somebody has been marginalized in a meeting, bring them up, it takes no time. For example, 'Chenoa, what do you think we can do next?' You're bringing that person to the table. Two, you can advocate for other women and minorities when they're easily interrupted in a meeting. This takes no time. ‘I'm sorry you interrupted Dr. Duma. Dr. Duma?' So, that helps. The third thing is very important. You can connect people. So, one of the things is that I don't have every skill, so I advocate for my mentees and I serve as a connector. I have a mentee that is into bioinformatics. Lidia, that's above my head. I don't understand any of that. So, I was able to connect that person to people that do bioinformatics. And follow up. My last thing is to follow up with your people because they need you. Dr. Lidia Schapira: Well, I'm very glad that you're not an oil engineer in the Emirates. I'm sure your family is incredibly proud. I hope that you're happy where you are. We started a little bit about where you started, I'd like to end with your idea of where you imagine yourself 10 years from now? Dr. Narjust Duma: That is a question I don't have an answer prepared for. I guess my career development plans I think I want to be in a place where I look back and I can see that the careers of my mentees being successful. And I think that we measure my success based not on myself, I would measure my success in 10 years based on where my mentees are. And medical education is a more inclusive place. That will be the two things I want to see in 10 years. In the personal aspect, I don't know if we have art, don't know if we have those grants as long as my mentees are in a better place. Dr. Lidia Schapira: It has been such a pleasure to have this conversation. Thank you so much, Narjust. Dr. Narjust Duma: Thank you. Dr. Lidia Schapira: Until next time, thank you for listening to this JCO's Cancer Stories: The Art of Oncology podcast. If you enjoyed what you heard today, don't forget to give us a rating or review on Apple podcasts or wherever you listen. While you're there, be sure to subscribe so you never miss an episode of JCO's Cancer Stories: The Art of Oncology podcast. This is just one of many of ASCO's podcasts. You can find all of the shows at podcast.asco.org. The purpose of this podcast is to educate and inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Narrator: My White Coat Doesn't Fit, by Narjust Duma, MD (10.1200/JCO.21.02601) There I was, crying once again all the way from the hospital's parking lot to my apartment, into the shower, and while trying to fall asleep. This had become the norm during my internal medicine residency. For years, I tried hard every day to be someone else in order to fit in. It started with off-hand comments like “Look at her red shoes,” “You are so colorful,” and “You are so Latina.” These later escalated to being interrupted during presentations with comments about my accent, being told that my medical school training in my home country was inferior to my US colleagues, and being assigned all Spanish-speaking patients because “They are your people.” Some of those comments and interactions were unintentionally harmful but led to feelings of isolation, and over time, I began to feel like an outsider. I came to the United States with the dream of becoming a physician investigator, leaving behind family, friends, and everything I knew. Over time, I felt pigeonholed into a constricting stereotype due to my ethnicity and accent. Back home, I was one of many, but in this new setting, I was one of a few, and in many instances, I was the only Latina in the room. I was raised by divorced physician parents in Venezuela; my childhood years were often spent in the clinic waiting for my mother to see that one last patient or outside the operating room waiting for my father to take me home. The hospital felt like my second home, growing up snacking on Graham crackers and drinking the infamous hospital's 1% orange juice. “She was raised in a hospital,” my mother used to say. Sadly, that feeling of being at home in the hospital changed during medical training as I felt isolated and like I did not belong, making me question my dream and the decision to come to the United States. I remember calling my family and crying as I asked “Why did I leave?” “Why didn't you stop me from coming here?” and seeking permission to return home. I felt like I was disappointing them as I was no longer the vivid, confident young woman who left her home country to pursue a bright future. I remember one colleague, Valerie (pseudonym), from Connecticut. Valerie attended medical school in the United States, did not have an accent, and was familiar with the American health care system. She understood how the senior resident-intern relationship functioned, a hierarchy that continually confused me. Over the following weeks, I took a closer look at how my colleagues and other hospital staff interacted with Valerie. I noticed that people did not comment about her clothing or personality. She was “normal” and fit in. I remember my senior resident asking me, “Narjust, why can't you be more like Valerie?” Ashamed, I mumbled that I would try and then ran to the bathroom to cry alone. That interaction was a turning point for me; I got the message. I needed to change; I needed to stop being who I was to be accepted. As the years passed, I kept key pieces of my personality hidden, hoping I could earn the respect of my colleagues. I refrained from sharing my personal stories as they were different from those around me. I grew up in a developing  country with a struggling economy and an even more challenging political situation. It was clear that we simply did not share similar experiences. When I sought help from my senior residents and attending physicians, my feelings were often minimized or invalidated. I was told that “residency is tough” and that I should “man up.” A few even suggested that I mold my personality to fit the box of what a resident physician was supposed to be. I slowly realized that my clothing changed from reds and pinks to greys and blacks because it was “more professional”; my outward appearance faded, as did my once bright sense of humor and affability. All these issues led to depression and an overwhelming sense of not belonging. A few months later, I was on antidepressants, but the crying in the shower continued. Rotation by rotation, I looked for a specialty that would help me feel like I belonged, and I found that in oncology. My mentor embraced my research ideas; my ethnic background or accent did not matter; we had the same goal, improving the care of our patients with cancer. I got to travel to national and international conferences, presented my research findings, and received a few awards along the way. From the outside, it looked like I was thriving; my mentor often called me a “Rising Star,” but in reality, I was still deeply depressed and trying to fit in every day. My career successes led me to believe that not being myself was the right thing to do. I felt isolated; I was trying to be someone I was not. A year later, I matched at my top choice oncology fellowship program; the program had the balance I was looking for between clinical care and research. This meant that I needed to move to the Midwest, further away from family, and to an area of the country with less racial and ethnic diversity. After 2 years on antidepressants and the 10 extra pounds that came with it, my white coat did not fit. My white coat felt like a costume that I would put on every day to fulfill the dream of being a doctor. I would often wake up in the middle of the night exhausted and depressed. I had all the responsibilities of a hematology/ oncology trainee and the additional full-time job of trying to fit in every day; I was using all my energy trying to be someone I was not. Regardless of my fears, I felt in my element when talking to patients and interacting with my cofellows. Despite having a different skin color and accent, I felt accepted by my patients with cancer. I remember when one of my patients requested to see me while in the emergency room because “Dr Duma just gets me.” She had been evaluated by the head of the department and attending physicians, but for her, I washer doctor. Tears of happiness accompanied my bus ride to see her; at that moment, I knew I was an oncologist, and oncology was the place I belonged. The next day, I realized that it was time to be myself: Narjust from Venezuela, a Latina oncologist who was her true self. I searched the bottom of my closet for the last piece of colorful clothing I had saved, a yellow dress. I put on that brightly colored dress for the first time in 5 years and finally felt comfortable being my authentic self; the yellow dress represented freedom and embraced the culture and colors I grew up seeing in my hometown. I finally understood that I brought something special to the table: my unique understanding of the challenges faced by Latinx patients and trainees, my advocacy skills, and my persistence to endure the academic grindstone. Psychotherapy was also an essential part of my recovery; I learned that happiness lived within me as a whole person—hiding my accent, cultural background, and past experiences was also hiding the light and joy inside me. Along the way, I found colleagues who faced the same challenges and validated that my experiences resulted from an environment that excludes the difference and values homogeneity. This route to self-discovery helped me find my calling to support others in situations similar to mine.3 I learned how to incorporate and celebrate my ethnicity in the world of academic oncology by teaching others the power of cultural humility, diversity, equity, and inclusion. Together with newfound friends and colleagues, I cofounded the #LatinasinMedicine Twitter community for those who face similar burdens during their training and careers. The #LatinasinMedicine community was created to share our stories, embrace our culture, and amplify other Latinas in medicine—to create connections that alleviate the sense of isolation that many of us have experienced and serve as role models to the next generation of Latinas in medicine. To help drive systemic change, I founded the Duma Laboratory, a research group that focuses on cancer health disparities and discrimination in medical education. Through research, the Duma Laboratory has shown that my experiences are not unique but rather an everyday reality for many international medical graduates and other under-represented groups in medicine. The Duma Laboratory has become a safe environment for many trainees; we seek to change how mentorship works for under-represented groups in oncology, with the hope that the isolation I felt during my training is not something that future physicians will ever have to endure. After years of depression and self-discovery, my white coat now fits. However, this is not your regular white coat; it has touches of color to embrace my heritage and the ancestors who paved the way for me to be here today. The face of medicine and oncology is changing around the world; young women of color are standing up to demonstrate the strength of our experiences and fuel the change that medical education needs. For all minority medical students, residents, fellows, and junior faculty, we belong in medicine even during those moments when our identity is tested. Through my journey, I learned that we can and must challenge the status quo. I hope to inspire others to join me in this path of advocating for diversity, equity, and inclusion because the time for change is now. I was finally free the moment I realized I could not be anyone else but myself, a proud Latina in medicine and oncology. Dr. Lidia Schapira: Welcome to JCO's Cancer Stories: The Art of Oncology, brought to you by the ASCO Podcast Network, which offers a range of educational and scientific content and enriching insight into the world of cancer care. You can find all of the shows including this one at podcast.asco.org. I'm your host, Lidia Shapira, Associate Editor for Art of Oncology and Professor of Medicine at Stanford. And with me today is Dr. Narjust Duma, Associate Director of the Cancer Care Equity Program and Medical Thoracic Oncologist at Dana Farber and an Assistant Professor at Harvard Medical School. We'll be discussing her Art of Oncology article, ‘My White Coat Doesn't Fit.' Our guest has a consulting or advisory role with AstraZeneca, Pfizer, NeoGenomics Laboratories, Janssen, Bristol Myers Squibb, Medarax, Merck, and Mirati. Our guest has also participated in a speaker's bureau for MJH Life Sciences. Narjust, welcome to our podcast. Dr. Narjust Duma: Thank you for the invitation and for letting us share our story. Dr. Lidia Schapira: It's lovely to have you. So, let's start with a bit of background. Your essay has so many powerful themes, the story of an immigrant in the US, the story of resilience, the story of aggression and bullying as a recipient of such during training, of overcoming this and finding not only meaning, but really being an advocate for a more inclusive and fair culture in the workplace. So, let's untangle all of these and start with your family. I was interested in reading that you're named after your two grandmothers, Narcisa and Justa. And this is how your parents, both physicians, Colombian and Dominican, gave you your name, and then you were raised in Venezuela. So, tell us a little bit about your family and the values that were passed on in your family. Dr. Narjust Duma: Thank you for asking. Having my two grandmothers names is something that my mother put a lot of effort into. She was a surgery resident with very limited time to decide to do that. And I don't have a middle name, which is quite unique in Latin America, most people in Latin America have one or two middle names. So, my mother did that to assure that I will use her piece of art, which is my first name. But little does she know that my grandmothers were going to be such an important part of my life, not only because they're in my name, but also because I am who I am thanks to them. So, the first part of my name, Narcisa was my grandma who raised me and she gave me the superpower of reading and disconnecting. So, I'm able to read no matter where I am and how loud it can be and disconnect with the world. So, it is often that my assistants need to knock on my door two or three times so, I don't like being scared because I'm able to travel away. That was also very unique because you will find me in the basketball games from high school or other activities with a book because I was able to block that noise. But it also makes very uncomfortable situations for my friends that find it embarrassing that I will pull a book in the basketball game. And as I grow, thanks to the influence of my grandmothers, I always have these, how can I say, mixed situation, in which they were very old school grandmothers with old school habits and values, and how I'm able to modify that. My grandma told me that you can be a feminist, but you still take care of your house. You can still, you know, cook. And that taught me that you don't have to pick a side, there is no one stereotype for one or another. Because as my mother being a single mother and a surgeon, my parents divorced early on, told me, ‘Yes, I can be the doctor but I can also be the person that has more than a career that's able to have hobbies.' I love cooking, and when I'm stressed, I cook. So, I had a grant deadline a few weeks ago and I cooked so much that there was food for days. So, having the names of my grandmothers is very important because I have their values, but I have modified them to the current times. Dr. Lidia Schapira: Let me ask a little bit about reading. I often ask the guests of this podcast who have written and therefore I know enjoy reading and writing, what their favorite books are or what is currently on their night table. But I'm going to ask you a second question and that is what languages do you read in? Dr. Narjust Duma: I prefer to read in Spanish. I found that books in Spanish, even if it's a book that originated in English, have these romantic characteristics. And I often tell my editors, ‘Just take into account that I think in Spanish, and write in English'. Because I grew up with Gabrielle Garcia Marquez, and when he describes a street, that's a page of the little things that he describes. So, that's how I write and that's how I read in a very romantic, elaborate way. The aspects of realistic imagism, which is my favorite genre in literature, and there are so many Latin American and South American writers that I don't think that I am going to run out. And when I run out, I reread the same books. I have read all of Gabrielle Garcia Marquez's books twice, and Borges, too. It's the type of stories that allows you to submerge yourself and you imagine yourself wearing those Victorian dresses in the heat of a Colombian street, as you try to understand if, you know, Love in the Time of Cholera, if they were more in love with being in love or what it was happening in the story. And that just gives me happiness on a Sunday morning. Dr. Lidia Schapira: That's beautiful. I must confess that reading Borges is not easy. So, I totally admire the fact that you have managed to read all of his work. And I think that you're absolutely right, that magical realism is a genre that is incredibly fresh, and perhaps for the work that we do in oncology, it's a wonderful antidote in a way to some of the realities, the very harsh realities that we deal with on a daily basis. So, let me ask you a little bit about growing up in Venezuela in the 80s, 90s, early aughts. That must have been difficult. Tell us a little bit about that, and your choice of attending medical school. Dr. Narjust Duma: So, growing up in Venezuela, with a Colombian mother, it was quite a unique perspective because she was very attached to her Colombian roots. So, a lot of the things that happened in the house were very Colombian, but I was in Venezuela. So, it was a unique characteristic of being from a country but your family is not from there. So, my parents are not from Venezuela, my grandparents either, and I'm Venezuelan because I was born and raised there. So, that brought a unique perspective, right? The music that I played in my house was Colombian music, not Venezuelan music. So, my family migrated from Colombia to Venezuela due to the challenges in the early 80s with violence and the Medellin, due to the drug cartels. So, we moved to Venezuela for a better future. And growing up in the first years, Venezuela was in a very good position. Oil was at the highest prices. Economically, the country was doing well. I remember, in my early years, the dollar and the bolivar had the same price. But then little by little I saw how my country deteriorated, and it was very heartbreaking. From a place where the shells were full of food to a place now when there is no food, and you go to the supermarket, and many of them are close. And now you're only limited to buying certain things. And you used to use your federal ID that has an electronic tracking on how much you can buy because of socialism. So, you're only allowed to buy two kilograms of rice per month, for example, you're only allowed to buy this number of plantains. So, every time I go home, because Venezuela is always going to be my home, it doesn't matter where I am., I see how my country has lost pieces by pieces, which is quite very hard because I had a very good childhood. I had a unique childhood because I was raised in hospitals. But I had a childhood in which I will play with my friends across the street. We were not worried about being kidnapped. We were not worried about being robbed. That's one thing that children in Venezuela cannot do right now. Children of doctors – there's a higher risk of being kidnapped as a kid right now if your father is a doctor or your mother. So, my childhood wasn't like that. When I teach my students or talk to my mentees, I'm often selling my country, and saying that's not what it used to be. That's not where I grew up. But every year I saw how it no longer is where I grew up. That place doesn't exist, and sometimes, Lidia, I feel like my imagination may have to fill it out with more good things. But I think it was a good childhood. It's just that nobody in Venezuela is experiencing what I experienced as a kid. Dr. Lidia Schapira: So, both parents were doctors and you chose to study medicine, was this just right out of high school? Dr. Narjust Duma: Even before high school, I found myself very connected to patients. So, since I turned 15, my father would give his secretary a month of vacation because that's the month that we fill in. So, I was the secretary for a month every summer since I was 15 until I was 20. That early exposure allowed me to like get to know these patients and they know I was the daughter, but I was also the secretary. So, I really cherished that. Growing up in my household, we're a house of service. So, our love language is acts of service. That's how pretty much my grandmas and my parents were. So, in order to be a physician, that's the ultimate act of service. I have wanted to be a doctor since I was 11. I think my mother face horrible gender harassment and sexual harassment as a female in the surgery in the early 80s, that she tried to push me away from medicine. Early on, when I was 11, or 12, being an oil engineer in Venezuela was the career that everybody should have, right? Like, people were going to the Emirates and moving to different parts of the world and were doing wonderful. So, my mother, based on her experience in the 80s, was pushing me away from it. She's like, ‘You can do other things.' My father always stayed in the back and said, ‘You can do what you want.' This is how our parents' experiences affect our future. If I wouldn't be this stubborn, I would probably be an oil engineer today, and I wouldn't be talking to you. Dr. Lidia Schapira: So, you went to medical school, and then after you graduated, what did you decide to do? Because when I look at what we know about the history there is I think you graduated in '09, and then the story that you write about sort of begins in '16 when you come to New Jersey to do training in the US, but what happened between '09 and '16? Dr. Narjust Duma: I started residency in 2013. '16 was my fellowship. So, going to medical school was one of the hardest decisions I made because right in 2003 and 2004 was a coup in Venezuela where part of the opposition took over the country for three days, and then the President of the time came back and the country really significantly destabilized after that coup. Most schools were closed. Entire private industries were closed for a month. And I think for some people, it's hard to understand what happened. Everything closed for a month, McDonald's was closed for a month. There was no Coke because a Coke company was not producing. Everything was closed. The country was just paralyzed. So, my mother and I, and my family, my father, took into account that we didn't know when medical school would resume in Venezuela. We didn't know if the schools would ever open again. I decided to apply for a scholarship and I left Venezuela at the age of 17 to go to the Dominican Republic for medical school. Very early on, I noticed that I was going to be a foreigner wherever I go because I left home. And since then, I think I became very resilient because I was 17 and I needed to move forward. So, that is what happened in 2004. I left everything I knew. I left for the Dominican. I do have family in the Dominican, but it was very hard because even if you speak the same language, the cultures are very different. And then I went to medical school in the Dominican and when I was in the Dominican Republic, I realized I really wanted to do science and be an advocate and focus on vulnerable populations with cancer. So, then I made the decision to come to the United States, I did a year of a research fellowship at Fred Hutchinson, and then I went to residency in 2013. Dr. Lidia Schapira: I see. And that's when you went to New Jersey, far away from home. And as you tell the story, the experience was awful, in part because of the unkindness and aggression, not only microaggression but outright bullying that you experienced. In reading the essay, my impression was that the bullying was mostly on two accounts. One was gender. The other was the fact that you were different. In this particular case, it was the ethnicity as a Latin or Hispanic woman. Tell us a little bit about that so we can understand that. Dr. Narjust Duma: I think what happened is that perfect example of intersectionality because we are now the result of one experience, we're the result of multiple identities. So many woman have faced gender inequalities in medicine, but when you are from a marginalized group, those inequalities multiply. I have an accent and clearly a different skin color. I grew up in a family in which you were encouraged to be your true self. My grandmothers and my mother said, ‘You never want to be the quiet woman in the corner because the quiet woman never generates change.' That's what they said, and I bet there are some who do. But that intersection of my identities was very challenging because I was seen as inferior just for being a woman and then you multiply being one of the few Latinas you are seen like you are less just because you are - it doesn't matter how many degrees or papers or grants you had done and all, I was the most productive research resident in my residency for two years in a row - but I would still be judged by my identity and not what I have produced, or what I do on my patients' experiences, which were great – the feedback from my patients. It's just because I was the different one. Dr. Lidia Schapira: When I hear your story about your origins, it seems to me that you came from a very capable loving family, and they basically told you to go conquer the world, and you did. And then you arrive and you're a productive successful resident, and yet, you are marginalized, as you say. People are really aggressive. Now that you've had some years that have passed, if you think back, what advice would you give that young Narjust? Dr. Narjust Duma: My number one advice, would be that, I will tell myself is that I belong, in many instances, I feel like I didn't belong. It makes me question all the decisions to that day because when you're doing a presentation, and I still remember like today, and you're interrupted by someone, just for them to make a comment about your accent, it really brings everything down to your core, like, 'Is my presentation not accurate? Is the information not all right? And why am I here? Why did I left everything I love to be treated like this?' Dr. Lidia Schapira: Of course. So, from New Jersey, you write in your essay that you really discover your passion for cancer research, and you land in a fellowship with a mentor who is encouraging, and things begin to change for you. Can you tell us a little bit about that phase of your training in your life where you slowly begin to find your voice in the state, that also where you crash, where you find yourself so vulnerable that things really fall apart? Dr. Narjust Duma: So, when I was a resident, I didn't know exactly - I was interested in oncology, but I wasn't sure if it was for me. So, Dr. Martin Gutierrez at Rutgers in Hackensack is the person who I cold emailed and said, ‘I'm interested in studying gastric cancer in Hispanic patients because I think that patients in the clinic are so young.' He, without knowing me or having any idea, he trusted me. We still meet. He still follows up with me. He encouraged me. I think him being a Latino made the experience better, too, because I didn't have to explain my experience to him. I didn't have to explain that. He understood because he went through the same things. And he's like, ‘I got you. Let's follow what you want to do.' He embraced who I was, and how I put who I was into my research. And thanks to Dr. Gutierrez, I'm at the Mayo Clinic as an international medical grad. So, finding a place in which my ideas were embraced was very important to allow me to stay in medicine because, Lidia, I can tell you several times, I decided to leave. I was very committed to finding something else to do or just being a researcher and leaving clinical medicine behind. So, when I went to Mayo, I still followed with that mentor, but I already knew what I wanted to do. I wanted to do cancer health disparities. I wanted to do inclusion and diversity. And that allowed me to develop the career I have now and is having that pathway because I, with my strong personality and everything else, faced this discrimination, and I can imagine for other trainees that may still be facing that or will face that in the future. So, I use the negative aspects to find my calling and do many things I have done after that. Dr. Lidia Schapira: Speaks to your strengths and your determination. Let's talk a little bit about the people who may also feel different but whose differences may not be so apparent. How do you now as an emerging leader, and as a mentor, make sure that you create an inclusive and safe environment for your younger colleagues and your mentees? Dr. Narjust Duma: One of the things that resulted was the founding of the Duma Lab, which is a research group that focuses on cancer, health disparities, social justice as a general, and inclusion in medical education. So, one of the things that I practice every day is cultural humility. I continue to read and remember the principles. I have them as the background on my computer at work. The number one principle in lifelong learning is that we learn from everyone and that we don't know everything and other people's cultures, and subculture, we learn their culture is rich. So, in every meeting, I remind the team of the principles of cultural humility when somebody is joining the lab. I have one-on-one meetings, and I provide information and videos about cultural humility because the lab has been created as an environment that's safe. We have a WhatsApp group that is now kind of famous - it's called The Daily Serotonin. The majority of the members of the lab are part of marginalized groups, not only by gender but race, religion, sexual and gender orientation. So, we created this group to share good and bads, and we provide support. So, a few weeks ago, a patient made reference to one of their lab member's body, the patient was being examined and that was quite inappropriate. The member debriefed with the group and we all provided insights on how she had responded, and how she should respond in the future. That's not only learning from the person that brought the scenario but anybody else feels empowered to stop those microaggressions and stop those inappropriate behaviors that woman particularly face during clinical care. So, cultural humility, and having this WhatsApp group that provides a place where, first, I remind everybody that's confidential, and a place in which anything is shared has been very successful to create inclusivity in the group. Dr. Lidia Schapira: You have such energy and I'm amazed by all of the things that you can do and how you have used social connection as a way of bringing people up. So, can you give our listeners perhaps some tips for how you view creating a flatter culture, one with fewer hierarchies that makes it safer for learners and for those who are practicing oncology? What are three quick things that all of us can do in our work starting this afternoon? Dr. Narjust Duma: The concept is that we all can be allies. And being an ally doesn't take a lot of time or money because people think that being an ally is a full-time job, it is not. So, the first one tip will be to bring people with you. Your success is not only yours. It's a success of your mentees. It's a success of your colleagues. So, don't see your success as my badge on my shoulder. It's the badge that goes on everyone. So, bring people in, leave the door open, not only bring them but leave the door open because when you do it helps the next generation. Two, little things make a difference. I'm going to give you three phrases that I use all the time. When you think somebody has been marginalized in a meeting, bring them up, it takes no time. For example, 'Chenoa, what do you think we can do next?' You're bringing that person to the table. Two, you can advocate for other women and minorities when they're easily interrupted in a meeting. This takes no time. ‘I'm sorry you interrupted Dr. Duma. Dr. Duma?' So, that helps. The third thing is very important. You can connect people. So, one of the things is that I don't have every skill, so I advocate for my mentees and I serve as a connector. I have a mentee that is into bioinformatics. Lidia, that's above my head. I don't understand any of that. So, I was able to connect that person to people that do bioinformatics. And follow up. My last thing is to follow up with your people because they need you. Dr. Lidia Schapira: Well, I'm very glad that you're not an oil engineer in the Emirates. I'm sure your family is incredibly proud. I hope that you're happy where you are. We started a little bit about where you started, I'd like to end with your idea of where you imagine yourself 10 years from now? Dr. Narjust Duma: That is a question I don't have an answer prepared for. I guess my career development plans I think I want to be in a place where I look back and I can see that the careers of my mentees being successful. And I think that we measure my success based not on myself, I would measure my success in 10 years based on where my mentees are. And medical education is a more inclusive place. That will be the two things I want to see in 10 years. In the personal aspect, I don't know if we have art, don't know if we have those grants as long as my mentees are in a better place. Dr. Lidia Schapira: It has been such a pleasure to have this conversation. Thank you so much, Narjust. Dr. Narjust Duma: Thank you. Dr. Lidia Schapira: Until next time, thank you for listening to this JCO's Cancer Stories: The Art of Oncology podcast. If you enjoyed what you heard today, don't forget

In part two this ASCO Education Podcast episode, hosts Dr. David Johnson and Dr. Patrick Loehrer continue their conversation with Dr. Richard Pazdur, director of the U.S. Food and Drug Administration's Oncology Center of Excellence, focusing on his leadership and vision for improving cancer care worldwide. The conversation includes reflection on drug toxicities, approval processes, and complexity of clinical trials. If you liked this episode, please subscribe. Learn more at https://education.asco.org, or email us at education@asco.org.   TRANSCRIPT Dr. Pat Loehrer: Hi. I'm Pat Loehrer, the Director of Global Oncology and Health Equity at Indiana University. Dr. Dave Johnson: And hi. I'm Dave Johnson at UT Southwestern in Dallas, Texas. Dr. Pat Loehrer: This is the second half of our Oncology, Etc. conversation with Dr. Rick Pazdur, who's the director of the FDA's Oncology Center of Excellence. In Part 1, we chatted with Dr. Pazdur about his upbringing and his early career. Today, we're going to focus on his leadership and vision for improving cancer care worldwide. But first, we'll discuss how cancer has impacted his life personally.   I want to flash-forward. I had the pleasure of knowing Mary. And there was no question, if you had a problem in oncology, you would go to Mary and not Rick Pazdur when you were a house staff member. But moving forward a bit, I'm not sure if all the listeners know that Mary came down with ovarian cancer. Dave himself had cancer. My wife had breast cancer. It is incredibly hard to be an oncologist I think when your spouse or someone who's close to you has cancer, and particularly, being married to a medical oncology nurse. Maybe just share a little bit about that journey of being a husband of a- Dr. Richard Pazdur: Yeah. It is interesting because going back to the Rush story, the first patient that my wife and I had in common, and this is so ironic, was a patient with ovarian cancer. The last patient that we had in common was her, which is some ironic fate, so to speak. And the story began of her illness was right around Labor Day. We had gone to Chicago in February driving back from Chicago. I noticed that she kept on taking a whole bunch of Tums and then saying - Oh, I just got a lot of GI symptoms, and she went to see her gastroenterologist or GP and he said, ‘Oh, this is just, you know, indigestion.' And two weeks after that or not even that, she was in the hospital with a massive amount of ascites, needed an intensive care unit. It was readily apparent just on getting her CA 125 what she had and she wound up one day in debulking surgery and then IP chemotherapy, etc. I think something that I learned, and I think we knew from the very beginning that this was not going to be a curable illness, and how to deal with that on an emotional level. And I have to give my wife credit. She spared me a lot of the emotion because she was such a strong person. She made all of her own calls as far as what she wanted. She would ask me what I thought, but she would do her own research, she would go to her own doctors' appointments. She said, ‘You don't really need to come with me. I'm self-sufficient.' She was very much interested in helping other cancer patients, and after she died, I think one of the most cherished conversations I had was a group of women that came to me and said how much she helped them during their support group because she was a nurse. She knew she was dying. She had emotional maturity not to fall apart but to accept the inevitable in a very strong way. My wife was a very religious person, had gone to Catholic schools, really embraced religion during those terminal years basically. And I think that was a great sense of comfort to her. But it did teach me a lot of lessons when you take care of somebody that has cancer, and that is, what a bad job we do with drug toxicities. Drug toxicities to medical oncologists and especially the people at the FDA are numbered, Grade 3, Grade 4, Grade 1. These toxicities are tolerable, tolerable to who, so to speak. And how to manage these toxicities and how they interrupt your life is one of the lasting experience I have, which I always will remember. And that has been one of my roles recently is forming several programs that we have in the OCE to look at dosing, to look at what is this definition if the drug is tolerable or well-tolerated or if the toxicities could be managed. I always say, yeah, every toxicity could be managed, even death. You call the undertaker to manage it. So what do you really mean by that statement. But I think the issue of toxicity is an important one. And then also going on clinical trials and having people considering what you want to go on, what risk you want to take, and what is actually in the informed consent and how meaningful that is. Dr. Dave Johnson: Really glad you brought that up, Rick. That matches my own experience with lymphoma and going through chemotherapy. And as an oncologist, one would think I would know what the side effects are. I'd recounted them dozens and dozens of times to people over the years, but until you've actually experienced them either personally or up close as you did with Mary, it's impossible to fully understand. I'll give you one example. Fatigue. Everybody thinks they know what fatigue is, but until you've had chemotherapy-induced fatigue, the fatigue that never abates, you just don't understand what it is. It's debilitating in ways that are unimaginable to most people. So I'm sure that experience certainly shaped your view and your role at the FDA. Dr. Richard Pazdur: Correct. Dr. Dave Johnson: I wonder, if you might share, you initiated a number of programs recently, including programs to try to improve coordination and co-operation amongst the pharmaceutical companies. Could you speak to some of those programs for us? Dr. Richard Pazdur: I think one of my favorite programs is Project Orbis. Project Orbis is an idea I had when I was walking down the street. It just hit me. When I came to the FDA, one of the things I rapidly noticed is how isolated the FDA was, even from the rest from the regulatory agencies throughout the world. There was very little cross-fertilization there. So one of the very first things that I did was set up a monthly tele-conference first with the EMA, the European Medicines Agency, and then we ended on Health Canada, Australia, Japan, Singapore, you name it. And one of the things that became really apparent to me, we at the FDA got applications always first—always. That's obvious. You know why they had given it to us first? The money. That's where the finances are going to be. So we got the application first, and it could be 2 years, 18 months, 12 months, that these other countries, Canada, Australia, Switzerland, and Brazil, Israel, would get these applications. And I said, well, this isn't right, really, because these people, they have cancer. They have every right to get these medications as soon as possible, and also we have such a large agency. We have 80 to 100 oncologists that work there, and most of these agencies have one or two oncologists. So our expertise in oncology at the FDA is so much greater than these other regulatory agencies. How can we leverage that to help these other countries? So we started Project Orbis, and what it was is that companies come in and they submit an application and they simultaneously submit the same application to the countries that want to participate in the program. They are all preselected and have confidentiality agreements with each other. And we worked together on the applications, basically reviewing the applications. So we had many meetings, tele-conversations, telephone conversations with countries. So that expedites these drugs. This has really had a lasting impact because from a worldwide perspective, it's really promoted more rapid development of drugs and rapid approval of drugs, and that's important because that establishes sooner new standards of care that will impact future trials. So in addition to the humanitarian issue of improving healthcare for patients in these countries, it has an impact on the global clinical trial system by having new standards approved much faster and accepted by world authorities. Dr. Pat Loehrer: Let me just jump on that for a second, just to make a comment. Back when we were growing up, there would be like three to five drugs approved- Dr. Richard Pazdur: Yeah. Dr. Pat Loehrer: And today, it's like once a week, there's a new indication for oncologists. Dr. Dave Johnson: Our listeners have another question that might be appropriate to ask at this time. What is the most common mistake that drug companies make in their applications to the FDA or in the process of trying to get their drug approved? Is there a frequent mistake that you can advise them? Dr. Richard Pazdur: Well, they don't come and talk to us. That's number one. They want, not necessarily what the best registration pathway is, but what the quickest registration pathway is. And sometimes the quickest registration pathway, especially single arm trials, are not the best registrations pathway. So my advice is rather than playing games with the FDA, to put it in the vernacular, just do the right thing and say, what is the optimal information that patients need when I develop this drug. We're seeing a lot of problems now with various drugs where people are developing in a refractory disease setting a drug, and they plan on getting accelerated approval on a response rate. So they push and push the dose. And with a single arm study, you can't really evaluate safety that well. Everything is attributed to the drug, and they want to get the highest response rate. And they get it, and there's a confirmatory study, and the arm of the confirmatory study, the control arm may not be as toxic as theirs, and we're seeing a wave of drugs that now have inferior survival compared to controls, which probably is predicated upon, they got the wrong dose. And I think that is one of the major programs that we have, that we need to address is dosing in oncology, this ‘More is better, more is better,' and ‘Let's push the dose as high as possible.' More isn't even probably good in cytotoxic days, but certainly, not a good idea in targeted therapies and certainly not a good idea in biological therapy. So we've really got to think about dosing more, penetration of targets, what's the optimal dose rather than what's the highest dose. You know as well as I do, pharmaceutical companies want to go with the highest dose because the major hurdle is the demonstration of efficacy, even in a randomized study. So nobody wants to be blamed by saying, well, you spent $100 million on a Phase 3 study and it's negative because you used too low of a dose. But then at the end of the day, we don't have a really good tolerable dose, and it's really hard to go backwards and look at dosing after a drug was already approved because the efficacy study has already been done. Dr. Pat Loehrer: The other aspect of drug companies is not only getting the dosage there, but also the duration. There is motivation for money, and so patients are going to and- Dr. Richard Pazdur: Oh, count on that. Dr. Pat Loehrer: So it begs a question, and I know the FDA can't do this, but in other countries, there is a monetary review together with the toxicity review. Can you reflect a little bit about that to the best of your ability? Dr. Richard Pazdur: Well, even within our simpler agencies, they may communicate more than we do with CMS, but all oncology drugs that when they're approved are then paid for by CMS, okay? In these other countries, that is not so. They may get approval and then they have to go to these health assessment agencies that will decide and argue with the companies what the pricing of the drug is. I think it's a mistake, honestly, for the FDA to get into pricing. We have a hard enough time with efficacy and safety, and pricing is a very ephemeral concept because it could change on a dialing. Somebody could promise you, you should approve their drug because it's much cheaper on Monday, and on Friday, they could say, 'Oops, we made a mistake. We really think that this dose has to be X number of dollars.' And you could see competition hasn't worked well in oncology with seven PD-1 drugs approved, pricing has not really been of any movement here. Dr. Pat Loehrer: I'm sorry. Dave may have another question, but let me ask you this. Going back to the clinical trials and what industry asked you- the complexity of clinical trials is going up logarithmically compared to the way they were in the ‘70s and ‘80s. In many of the trials where we have to get all this data in order to soothe the FDA, what are your thoughts about simplifying clinical trials? Dr. Richard Pazdur: Oh yeah. I'm for it. I am for it. If you really look at it, these are not FDA requirements for the most part. The companies want them, all of this data because it's controlled. They don't want to be blamed at the end of the day for not capturing this data or that data. They have developed complicated bureaucracies, going back in my sociology days there, complicated bureaucracies to gather all of this data, the whole CRO industry to go out and pester you guys in practice by doing site visits. It's a complicated situation and it's really predicated a lot on the history and bureaucracies that have been built up and not money to strip away those bureaucracies for fear of failure, so to speak, of not catching something. Dr. Dave Johnson: So Rick, we're coming to the end of our time that we've scheduled. I actually have two questions for you. We've asked all of our previous guests, the first of which would be if you could talk to your 21-year-old self today, what advice would you give yourself? After you've done that, we'd like to know what books have you been reading lately or is there some documentary that you've seen that you would recommend to us and our listeners? Dr. Richard Pazdur: I would tell myself, when I was 21 years old, relax and be less anxious. All things pass. I think we get so anxious when we're young about relatively small things. I remember my first ASCO presentation, I was petrified. My heart was beating out of my chest. I was sweating. And like relax. It's one of a thousand presentations at ASCO. We tend to magnify things, and I think age puts things in perspective. This in the reality of the world is a small thing, and people probably won't even remember it. Dr. Dave Johnson: Excellent advice. Dr. Richard Pazdur: My favorite author that I'm reading now for the last couple of months is a presidential historical author, Doris Kearns Goodwin. I think many of you know, she's written many books. I love her writing style. And I like non-fiction. I like biographies and I like history books, history stories rather than mysteries or things like that, fantasy books. The two books that I really enjoyed, the first one was No Ordinary Time: Franklin and Eleanor Roosevelt: The Home Front in World War II. I don't know if anybody's read that. It's an excellent book. Most of our attention in World War II is directed toward Europe and what was going on in Europe, the battlefields, etc., which I'm not a big fan of reading about battles and stuff, but this was what was going on in The White House and the relationships of all of the people that came there. It was like a hotel almost with the personalities that were flowing through including Churchill and various princes and queens, etc. But also the interesting relation, the fascinating relationship that Eleanor and Franklin Roosevelt had, I don't know how to describe the relationship. It truly was an unconventional relationship based on some past history that they had of affairs etc., but it was just a fascinating one. The best book, though, again I'm reading now, is written also by Doris Kearns Goodwin, and it is Lyndon Johnson and the American Dream. Doris Kearns Johnson was his biographer and spent a great deal of time with him in The White House as well as when he left The White House. But it's an excellent book on management and reading people, success. One of the things that is most interesting about Lyndon Johnson, and especially when he was running the senate before he became president, was his ability to know what motivated people and how to use that to form a consensus. Does this person want to go on this trip. I'll give it to him and then he could help me with this. Does this person want to go to this party or get on this position in congress? So it was really a skillset that he had, which I think most leaders need to know. You have to motivate people. You can't lead by an autocratic masthead, but you've got to lead from what do people want and to make sure that they feel you have a personal relationship with them. As I say to my staff, everything in life is personal—everything. Dr. Dave Johnson: Well, it's been a great session, Rick. We so much appreciate your willingness to spend time with us. We wish we had twice as much time. I'm sure we could go on for hours. Thanks again, and we appreciate all you do at the FDA. You've been a fabulous leader, and we hope you continue on for many years to come. Dr. Richard Pazdur: Thank you so much, Dave, and thank you so much, Pat. Dr. Pat Loehrer: Great to see you. Dr. Dave Johnson: Pat, before we leave, any idea why our patients seem to get sick on Saturday and Sunday? Dr. Pat Loehrer: I have no clue. Do you know the answer, Dave? Dr. Dave Johnson: Yes. They have a weekend immunity. Thank you for listening to the ASCO Education Podcast. To stay up to date with the latest episodes, please click subscribe. Let us know what you think by leaving a review. For more information, visit the Comprehensive Education Center at education.asco.org. 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.    

The role of pathologist in the diagnosis and treatment of melanoma is pivotal to optimal patient care. With so many disciplines relying on the pathologist for accurate diagnoses and critical pathological information, we decided to reach out to our clinical melanoma community to ask them for their critical pathology questions.In this podcast, Prof John Thompson AO and Prof Fergal Moloney pick at the brain of the world's leading melanoma Pathologist, Prof Richard Scolyer AO, as they discuss:The clinical information needed to aid diagnosisThe role of artificial intelligence and computing in pathologyOverdiagnosis of melanomaThe problem of partial biopsiesDiagnosing borderline lesionsWhat is a melanocytoma and how should it be managedWhat is an irritated naevusDysplastic naevi and appropriate managementThis podcast is suitable for GPs, Dermatologists, Surgeons, Oncologists, Pathologists and other healthcare professionals.SPEAKERSProf Richard Scolyer AO - Co-Medical Director, Melanoma Institute Australia | Pathologist, Melanoma Institute Australia, Senior Staff Specialist, Royal Prince Alfred Hospital | Clinical Professor, The University of SydneyProf John Thompson AO - Emeritus Professor of Melanoma and Surgical Oncology, The University of Sydney | Member, Melanoma Institute AustraliaProf Fergal Moloney - Consultant Dermatologist, Melanoma Institute Australia and Mater Misericordiae University Hospital | Clinical Professor, University College, DublinPlease note that this podcast was accurate at the time of recording (June 2022) but may not reflect the rapidly evolving treatment landscape and approvals in Australia.For more practice-changing education, visit our Melanoma Education Portal.MIA's Education Program is proudly supported through unrestricted educational grants from: MSD, Bristol Myers Squibb, Novartis and HEINE.

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

The ability to critically appraise the validity of published literature is an essential skill for all physicians. This lecture will explore the principles of evidence based medicine with a focus on critical appraisal of randomized controlled trials.

Suneel D. Kamath, MD, of the Cleveland Clinic Taussig Cancer Institute in Cleveland, Ohio, spoke with the editorial team of the journal ONCOLOGY® about his published manuscript titled, ‘Association of Financial Conflicts of Interest With Academic Productivity Among Junior Faculty in Hematology and Oncology.'  Suneel and colleagues set out to determine how financial conflicts of interest could be used as a surrogate for the trajectory of early-career oncologists and junior faculty at academic institutions. He touched on how understanding relationships between clinicians and industry is important for both drug development as well as the early academic productivity of individual investigators. Don't forget to subscribe to the “Oncology Peer Review On-The-Go” podcast on Apple Podcasts, Spotify, or anywhere podcasts are available.

When your dog has cancer, there are a lot more people on her care team than just you and the oncologist. Veterinary technicians – including ones who specialize in oncology – are another layer of medical professionals ready to help your dog. Jenny Fisher, Registered Veterinary Technician and Veterinary Technician Specialist in Oncology, was the Head Technician in Oncology at Louisiana State for 14 years. Fisher explains what vet techs do in the hospital, the education they have undergone, and the struggles of working in this profession. She also explains why vet techs aren't called veterinary nurses in the US, and untangles some of the different credentials used in various states. Links Mentioned in Today's Show: Academy of Internal Medicine for Veterinary Technicians National Association of Veterinary Technicians in America American Association of Veterinary State Boards Related Links: Cancer Treatment Unit at Louisiana State University How to Meditate With Your Dog (the Maui the dog story) About Today's Guest, Jenny Cassibry Fisher: Jenny has worked in veterinary medicine in some regard for over 25 years, receiving her RVT in 2002 and her VTS (IM-oncology) in 2015. Her clinical experience includes academia, general medicine, and emergency medicine. Jenny serves as the president-elect for the Academy of Internal Medicine for Veterinary Technicians (AIMVT). LinkedIn Other Links: To join the private Facebook group for readers of Dr. Dressler's book “The Dog Cancer Survival Guide,” go to https://www.facebook.com/groups/dogcancersupport/  Dog Cancer Answers is a Maui Media production in association with Dog Podcast Network This episode is sponsored by the best-selling animal health book The Dog Cancer Survival Guide: Full Spectrum Treatments to Optimize Your Dog's Life Quality and Longevity by Dr. Demian Dressler and Dr. Susan Ettinger. Available everywhere fine books are sold. Have a guest you think would be great for our show? Contact our producers at DogCancerAnswers.com Have an inspiring True Tail about your own dog's cancer journey you think would help other dog lovers? Share your true tail with our producers. If you would like to ask a dog cancer related question for one of our expert veterinarians to answer on a future Q&A episode, call our Listener Line at 808-868-3200 www.dogcanceransers.com. Dog Cancer News is a free weekly newsletter that contains useful information designed to help your dog with cancer. To sign up, please visit: www.dogcancernews.com Learn more about your ad choices. Visit megaphone.fm/adchoices

Health equity means that everyone has a fair and just opportunity to be as healthy as possible, despite their cultural or demographic background. But achieving this means removing obstacles to health, such as discrimination, economic disadvantages, and lack of access for certain populations and communities. Today's guest Omatola Gordon-Rose, Senior Director of Health Equity Initiatives at Komen, understands how multiple barriers combine to create breast health inequities in the black community, and is here to share how the program Stand for H.E.R. A health equity revolution addresses these inequities through several tailored interventions. Omatola, welcome to the show.

“Liquid biopsy” is a form of cancer screening that detects biomarkers in the blood with a simple draw. Research indicates that it could help to detect disease months or even years before other, more expensive and more invasive forms of screening, helping to save lives. So how exactly does it work? Is it better at detecting some cancers compared to others? And how can it help oncologists treat already diagnosed cases? Medcan's director of clinical innovation, Allison Hazell, investigates with the help of Dr. Lewis Roberts, director of the Mayo Clinic's Hepatobiliary Cancer Lab. Check out the episode webpage for links and more info.

Charlotte Cush is the current reigning Ms Galaxy Australasia 2022. After being crowned in 2020, it has been a long wait for Galaxy Internationals with competition taking place in McAllen, Texas this coming August. Growing up on the beautiful beaches of the Gold Coast, Charlotte grew up around the water with her five siblings. Her love for the water grew into a passion for competitive swimming. Her athletic and highly competitive nature also branched out into touch football, netball and cross country running representing her state in each discipline throughout her schooling. Charlotte attributes her drive, commitment, dedication and passion for health and fitness to her diverse athletic upbringing. Retiring from swimming at the age of 18, she took up Remedial massage and Beauty Therapy and worked alongside some of the most iconic names in the industry such as the Versace Day Spa and Ella Bache. Realising that beauty and health was more than just skin deep, her passion for health and helping people evolved into a medical interest. She started studying her Bachelor of Nursing full-time and after three years of studies landed herself a post-graduate position at one of the most prestigious hospitals in Queensland in the Oncology and Haematology ward. Since then she has also completed a double specialty in Apheresis and Stem Cell collection techniques. She teaches nursing students and has spoken at state conferences for drug companies. Now in her eighth year of nursing, she couldn't think of a better profession than one that saves lives and supports the health of her community. Charlotte has blossomed into a well-rounded pageant competitor with a whole lot of heart who challenges the public's old school ideations of who and what a pageant girl really is. Educated, strong and fearless with a pinch of sass. She aims to use her platform to help young women attain a healthy mentality towards fitness and health, and to work closely with the Cancer Council raising money for cancer research. ---⠀ ⠀ Be more than just a queen. Make an IMPACT. Join our sorority:⠀ ⬇️⬇️⬇️⠀ http://thepageantsorority.com/

Featuring perspectives from Ms Paula Anastasia, Dr Robert Coleman, Dr David O'Malley and Ms Jaclyn Shaver, including the following topics: Introduction (0:00) Management of Endometrial Cancer (5:32) Treatment for Cervical Cancer (45:31) COVID-19: Considerations in Cervical and Endometrial Cancer (1:22:34) Oncology 2032 Crystal Ball (1:27:43) CME information and select publications

At the start of 2022, Oncotarget began publishing research papers in a continuous publishing format in yearly volumes. As of June 23, 2022, Oncotarget has published a total of 64 high-impact, oncology-focused papers within Volume 13. Oncotarget's Volume 13 consists of papers authored by numerous prestigious researchers and scientists from world-renowned institutions. Select papers in this Volume were chosen for inclusion in Oncotarget's Special Collections on breast and lung cancer research. Read the full press release - https://www.oncotarget.net/2022/06/23/oncotarget-new-oncology-focused-papers-published-in-volume-13/ Visit www.Oncotarget.com to read the latest publications in Volume 13. About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. To learn more about Oncotarget, visit Oncotarget.com and connect with us on social media: Twitter – https://twitter.com/Oncotarget Facebook – https://www.facebook.com/Oncotarget YouTube – www.youtube.com/c/OncotargetYouTube Instagram – https://www.instagram.com/oncotargetjrnl/ LinkedIn – https://www.linkedin.com/company/oncotarget/ Pinterest – https://www.pinterest.com/oncotarget/ LabTube – https://www.labtube.tv/channel/MTY5OA SoundCloud – https://soundcloud.com/oncotarget For media inquiries, please contact: media@impactjournals.com.

In this week's episode we'll learn more about salvage therapy with nivolumab plus or minus ICE (or NICE) for Hodgkin lymphoma, discuss the role of BMP2/SMAD pathway activation in leukemic transformation, and learn more about the role of zinc in T-cell reconstitution after transplantation.

Dr. Diwakar Davar and Dr. Jason Luke, both of the University of Pittsburgh's Hillman Cancer Center, highlight key advances in early phase therapeutics and immunotherapy that were featured at the 2022 ASCO Annual Meeting and also address toxicities, including immune checkpoint inhibitor-associated myocarditis. TRANSCRIPT Dr. Diwakar Davar: Hello, and welcome to the ASCO Daily News Podcast. My name is Dr. Diwakar Davar, and I'm an assistant professor of Medical Oncology, specializing in melanoma and phase 1 therapeutics at the University of Pittsburgh's Hillman Cancer Center. I am the guest host of today's podcast. My guest today is Dr. Jason Luke, a colleague and the director of the Cancer Immunotherapeutics Center at the UPMC Hillman Cancer Center here.  Today, we'll be discussing advances in early-phase therapeutics and immunotherapy that were featured at the 2022 ASCO Annual Meeting.   You'll find our full disclosures in the show notes, and the disclosures of all guests on the podcast are available on our transcripts at asco.org/podcasts.  Jason, thank you for coming on the podcast today.  Dr. Jason Luke: Thanks so much for the invitation. It was a great ASCO, and I hope everyone had a good time.  Dr. Diwakar Davar: So, onto our abstracts. So, the first one that we'll be discussing, and Jason as you know we've done this before. We'll be rapidly transitioning between phase 1 therapeutics, melanoma, and advanced phase 2 and 3 trials, but you know this is something you do very well. So Abstract 2504, it's a phase 1 trial of TIM-3 inhibitor cobomilab immunotherapy and in combination with PD-1 inhibitors nivolumab and dostarlimab. The AMBER Trial that was presented recently, and in full disclosure, both you and I actually are on this abstract. So, what do you think of this abstract? What do you think of the data that is discussed, and how do we contextualize this in relation to what needs to be done in this space?  Dr. Jason Luke: So, I think this is an exciting abstract because it brings forward what may be the next high-priority immune checkpoint to try to target in clinical oncology. To level-set, I think everybody listening will know about PD-1 and CTLA-4 as immune checkpoints. In the last year, we've had LAG-3 come forward as now a standard of care element of armamentarium in melanoma, and we look forward to further studies of LAG-3 and other tumor types as we think it should be a good partner where PD-1 is otherwise approved.  So here now, we hear about TIM-3, which is another negative regulatory checkpoint on a number of different immune subsets. And in this abstract, the antibody targeting TIM-3 was cobolimab. So, TIM-3 is a very interesting molecule. It has, what you might call, pleiotropic effects in the immune system. So, while in the context of this abstract, it was being targeted as another immune checkpoint on T cells, it's important to point out that TIM-3 has other regulatory roles in other immune subsets such as myeloid cells and very particularly dendritic cells, and that's important because it might bring in another element of the innate immune system to try to drive anti-tumor responses. So, it's an exciting target because it might be able to expand the groups of patients who could benefit from immune checkpoint blockade.  So, in this abstract, we see initially the phase 1 data of combining cobolimab, anti-TIM-3 with anti-PD-1 of a couple of different flavors. And what you could take from this abstract is that in the phase 1 setting, the drug was well-tolerated and combined well, and had pharmacokinetic properties that would be consistent with what we'd expect for this kind of a monoclonal antibody. I think we have to marry this abstract, which is really the phase 1 data about safety in pharmacokinetic (PK) to another abstract presented in the melanoma session, which showed an expansion cohort of patients who got cobolimab plus nivolumab or dostarlimab.  And there we did see a 50% response rate, albeit that there was heterogeneity of patients being treatment naïve versus treatment-experienced. So, what I would say to this on a high level is that I think these data are preliminarily exciting, suggesting that further investigation into TIM-3 may be valuable in terms of expanding the population of patients initially in melanoma, but there will data coming soon in lung cancer and in other tumor types with another novel checkpoint. And I think if we think ahead into the future, the question is probably going to end up being, which combinations of checkpoints for which patients. That's pretty exciting to think about. We've seen a lot of data of PD-1 plus other molecules, and I think some future biomarker stratification really will be necessary to know which patient would benefit the most from which of these combos, but for the time being, this is exciting data to see where the field is going to go over the next couple of years.  Dr. Diwakar Davar: Great. And I guess, to your point, one important thing to highlight from the abstract is your point about the role of the different compartments. There was actually a very interesting dose-response relationship with the highest dose of the drug not necessarily being the most effective dose, suggesting that yes, as you escalate, you may have different effects in different compartments, and maybe therefore a broad selection of doses might be required to ensure that you have optimal engagement of the optimal target.  So, the next abstract is Abstract 3007. This is the tumor-agnostic efficacy and safety of erdafitinib. So, we now know that FGFR pathway aberrations are found from 77% of all malignancies, FGFR targets are now U.S. Food and Drug Administration (FDA) approved in cholangiocarcinoma with pemigatinib, infigratinib, and as well with erdafitinib metastatic urothelial cancer. We know that these agents are not necessarily effective tests in 1 tumor type because these alterations have risen in multiple tumor types. So, the RAGNAR trial, looking at this across multiple tumor types, what do you make of the interim analysis result presented by Dr. Loriot?  Dr. Jason Luke: So, I'd say that this is probably the future of targeted therapy. And so, I think that where we have activity in 1 disease, it's very likely we would have activity in others. So, the author has described this as the largest basket trial of a molecularly defined subset that's been pursued to date. There are upwards of more than 200 patients in the study. I think it's really important, as we think about the data, to realize, though, that all FGFR alterations are not exactly the same thing. And so, in this study, they gave erdafitinib to patients with solid tumors of any FGFR altered status. And so that's FGFR1, 2, 3, 4 mutations or gene fusions. And that's a lot of heterogeneity in there actually.  And in this study, there were two-thirds fusions and one-third mutations, mostly in FGFR2 and 3. That will become relevant as we start to think about the results. On a high level, I have to say that it is impressive in pan-cancer fashion, just selecting by FGFR alteration, there's about a 30% response rate observed. I think that no matter what, that's going to be valuable considering these were patients with refractory tumors with 3 lines of prior therapy on median. I think what we need to know more is the breakdown of which specific molecular alteration and FGFR in which tumor types drove most of the benefit.  So, for example, in bladder cancer where erdafitinib is already approved, that's almost entirely an FGFR3 fusion setting. So we know the drug is effective there. And so I think there will be a further breakdown of the data. As it matures more, you really start to tease out, is it really the case that any FGFR alteration can be treated or there are some that really ought to be the high priorities that we really ought to be going after. I think it would be remiss not to also note, however, that while there's excitement about this sort of pan-cancer approach, the current generation of FGFR inhibitors are not exactly the easiest drugs to take.  And so, the in-class, hypophosphatemia and stomatitis really does lead to dose reductions in a lot of the patients. And I think that that's probably really important to emphasize is that despite the pan-tumor activity, there's still a lot of potential in this field to refine further because it's almost certainly the case that if we had less off-target toxicity, so to say, we could improve the efficacy beyond that 30% that we saw here.  All the same, I think this is exciting for the concept of a pan-cancer tumor agnostic sort of approach, and we'll really look forward to more data to come from this study over the next, hopefully, few months.  Dr. Diwakar Davar: And I guess 1 corollary to that is that we now need to start looking for FGFR alterations in multiple tumor types. So, tests, tests, tests. All right, Abstract 3004, phase 1a/1b dose escalation and expansion study of the MDM2-p53 antagonist BI 907828 in patients with multiple solid tumors including advanced, metastatic, liposarcoma. So, we've recently had data of the previously undruggable KRAS, and now we've got previously undruggable p53, for which we now have targets. So, Jason, what do you make of the p53 targeting approach, in this case, using MDM2 and this particular drug from Boehringer Ingelheim?  Dr. Jason Luke: So, I think that this is an exciting abstract exactly for the reason that you mentioned, which is that p53 has been, and unfortunately, to some degree, still remains, one of those holy grails but undruggable targets in oncology. So MDM2, for those who are listening but might not be aware, is a negative regulator of p53. So, the concept here then is if you drug it, you might release p53 to reactivate activity in that pathway, and then p53 being the guardian of the genome, so to say, potentially leading to apoptosis of cancer cells.  And so, this drug binds MDM2 and MDM2 can be amplified as a resistance mechanism in p53 and several tumor types. And so here, they showed data for the early part of a clinical trial investigating the small molecule, BI 907828, but then they focus specifically in liposarcoma, which is a disease known to be an MDM2 amplified. And so, the results were pretty interesting. The toxicity of this kind of an approach, just to note, is really in class. It leads to some gastrointestinal (GI) toxicities as well as hematologic problems, and this goes again for most regulators of the cell cycle will have these effects, whether they're CDK inhibitors or MDM2 or p53 modulators.  But I think what was very interesting, this is a disease liposarcoma where chemotherapy, functionally speaking, has no role. We, unfortunately, give it to some patients sometimes, but it has almost no activity, and they observe that in poorly differentiated liposarcomas, the response rate was about 12%, but the stable disease was quite durable. And so, I think that really is potentially a big deal because this is an orphan disease. It really lacks any other treatment. But as you zoom out from that, if you start to think about targeting amplified MDM2 in other settings, I think the activity that we see here is intriguing, and potentially suggests that we may be coming to a future where we'll have multiple, sort of, orthogonal approaches after reactivating p53. There were actually other abstracts at ASCO Annual Meeting of other molecules that were less mature also along this line.  So, I think, very exciting to take away from this, one, a potential treatment for liposarcoma for all of those patients that anybody listening actually sees, but secondarily this concept of targeting p53, which I think we'll see a lot more of over the next couple of years.  Dr. Diwakar Davar: Excellent. Moving on to the Abstract 3002, this is a phase 1, two-part multicenter, first-in-human study of DS-6000a of an antibody-drug conjugate comprising the anti-CDH6 IgG1 monoclonal antibody that is attached to a topoisomerase I inhibitor payload via a cleavable linker. And so basically, a way in which you can give topoisomerase: (1) TOP1 inhibitor, (2) CDH6-expressing cells. This was studied in advanced renal cell carcinoma (RCC) and advanced ovarian cancer in this abstract presented by Dr. Hamilton. Jason, what do you think of the results and what do you think of this approach in general, this antibody-drug conjugate (ADC) approach using novel targets as well as novel payloads?  Dr. Jason Luke: I think this is one of those that you can't help but be pretty excited about, and I think in the context of the data shown at the plenary session in breast cancer for antibody-drug conjugates (LBA3), I think this is really where the field is going to start to go. So, you mentioned that this is an antibody-drug conjugate that targets cadherin 6 or CDH6, which people will remember from biochemistry class and medical school, or something is a cell-cell adhesion molecule, really a basement membrane protein. So, the concept of targeting it really is just to go after a latch mechanism to get the molecule into the tumor where you want. And CDH expression is very high in renal cell carcinoma, upwards of 80% of samples, also high in ovarian cancer, which is why they chose those 2 tumors to go after.  So, the ADCC, and you described its structure just a little bit, but it's essentially the same backbone as trastuzumab deruxtecan, which we saw this outstanding activity for HER2 and breast cancer on the plenary, with these 8 chemotherapies moieties attached to it, but here now, targeting it instead to HER2, with this molecule now to CDH6. And I think, again, you can't help but be impressed. There were treatment responses on almost every dose level of the dose escalation in this study. There's in fact only 1 patient whose tumor was not, at least, stable disease or a PR, and I think that that just goes to show the power of truly bringing the chemotherapy in a targeted manner into the tumor microenvironment. Responses were heterogeneous. They were not super deep responses per se, but the stable disease was quite durable in the study, and the patients were going out more than 7 months. And again, realizing this is at the lower dose levels as we're increasing the dose and move this in their earlier lives of therapy is likely to be even more effective.  They did show a waterfall plot of the reduction in CA 125 for the patients with ovarian cancer that really looked quite impressive. And given that that's our clinical biomarker that we commonly follow, it may actually even more indicative of the benefit we would see as opposed to resist.  Now, again, there is some toxicity. It is a chemotherapy moiety that's conjugated to the ADCs. So, the most common toxicities were nausea, vomiting, and low platelet counts, but these are kind of toxicities that we're quite accustomed to with chemotherapy. Just to summarize, I think there's a lot of promise for this kind of antibody-drug conjugate targeting, and I think it can only be impressive that they had this amount of activity in the dose escalation of the study. [I] very much look forward to the expansion cohorts in renal and ovarian, which we'll presumably expect to see later this year, early in the next year.  Dr. Diwakar Davar: And as you alluded to, this really was parallel that ASCO, by the standing ovation given to Dr. Modi when she presented the DESTINY04 data of trastuzumab deruxtecan in HER2-low breast cancer, basically now redefining breast cancer from 4 camps, now we have to think of not just HER2 amplified or HER2-high, but also HER2-low. So yes, really have to now rethink how we classify these diseases (LBA3).  So Abstract 2509, the efficacy of anti-PD-1/PD-L1 immunotherapy in non–small cell lung cancer dependent based on CD8 and PD-L1 status. So really Dr. Galon taking us into what he has now described as the immunoscore—really a way of characterizing tumors. A way of thinking about tumors that you've also championed, Jason, in terms of this T cell-inflamed and uninflamed hypothesis. So, tell us a little bit about how these jives with your work and how you would think about lung cancer patients responding and not responding to immune checkpoint inhibitors (ICI) therapy in this context?  Dr. Jason Luke: Yeah. I think the focus quickly here on the immunoscore, so the people are aware of that, I think is really important for diving into these specific results. You have to realize our fundamental underlying predicate for immune checkpoint blockade inhibitor response is that patients have mounted an adaptive immune response. So, CD8 T-cells have gone into the tumor where they elaborate chemokines and cytokines like interferon gamma, which upregulates the expression of PD-L1 in the tumor but also in the surrounding immune cells.  So, you realize that even though antibodies are targeting PD-1, it's really that we're targeting that tumor microenvironment. So, the more robustly we can measure that, and we understand it, the more likely we are to know whether or not the patient is going to benefit. So, this is where the immunoscore comes in. The immunoscore is actually a fairly simple test. It's one slide, immunohistochemistry slide where they can stain jointly for CD8 and PD-L1 on the same slide. And that allows them to do a number of different things beyond just testing the total level of PD-L1. They can test the CD8 density, the PD-L1 expression, but then also the interaction between CD8 T-cells, their distance from each other, from PD-L1 expressing cells, and so on and so forth.  And so really [this] can give us a much more robust analysis of what all is going on in the tumor microenvironment again, off of a single slide. So here then, in this abstract, for patients with non–small cell lung cancer receiving anti-PD-1, they then compared the utility of only PD-L1 testing versus doing the immunoscore. And so, it was actually quite a large set. They had about 250 patients in their analytical set and then split about 150 or 180 or something into the training and validation sets, and they compared the immunoscore against 2 different standard PD-L1 antibodies, the 22C3 as well as the SP263. And what they saw was a high concordance for expression between PD-L1 and the immunoscore.  That's good, because, again, they're measuring PD-L1 in both of those. And so that was a good, sort of, level set. The immunoscore, however, allows them to look to 7 different parameters, again, beyond just PD-L1, as I mentioned. So, CD8 density, interaction, distance, and this kind of thing. Then in these test and training cohorts, they were able to actually split out patients who are PD-L1 positive into further groups, those that were immunoscore low and that were high. And in so doing, they were actually able to sort of dramatically predict the likely progression-free survival on PD-1 checkpoint blockade in those different non–small cell lung cancer groups.  So why is this important? Selection of patients by PD-1 has been very useful in the field of non–small cell lung cancer, but it's hardly a panacea. You're not at all assured your patient is going to do well just because they're PD-L1. And here comes a second assay that can be done in a standard of care setting. So, the immunoscore is a test. You could just order it, and that really does give you much more predictive power about who's likely to do well and who isn't. And I think this test and more broadly multi-spectral imaging is really going to become a core component to how we risk stratify and predict outcomes to checkpoint blockade and lung cancer, but broadly in other tumor types over the next couple of years.  Dr. Diwakar Davar: Okay. Now, moving on from a biomarker for PD-L1 and PD-1 to a setting in which PD-1 was just recently U.S. Food and Drug Administration (FDA)-approved, so I'll give a brief background to the trial that you've actually developed and led. And so, this is KEYNOTE-716, the abstract in question is LBA9500 (late-breaking abstract) 9500, but this is the distant metastasis-free survival (DMFS) data readout. The DMFS, distant metastasis-free survival with pembrolizumab versus placebo in the adjuvant setting for patients with stage IIB or IIC, that is high-risk node-negative melanoma and the data from the phase 3 KEYNOTE-716 study.  So, this data, at least the recurrence-free survival (RFS) data was actually earlier published, you had presented it earlier last year and also more recently this year, but it was published recently in Lancet. And we know that 716 is a study in which, for the first time ever, we have an immune checkpoint inhibitor PD-1 that was studied against placebo with the high-risk node-negative setting in stage IIB and C melanoma, demonstrated a significant RFS benefit in the setting against placebo. And now we have the DMFS readout.  Maybe you could tell us a little bit about both the RFS and the DMFS data, and why this is such an important advance for these patients.  Dr. Jason Luke: Thanks. And I agree this really is a sea change in how we thought about stratification of patients with melanoma, but I think this broadly has implications for other tumor types as well. So, in melanoma, we've historically thought of its involvement of the lymph nodes—stage III as being the high-risk disease, but we also, if you look at the outcomes from the AJCC, we see the patients with stage IIB and IIC, so deep primary lesions, actually have similar bad outcomes as those patients with stage IIIA and IIIB. And so anti-PD1 and adjuvant therapy and melanoma were originally proved for stage III, but having understood that about 5 years ago actually, started to think, well, why not also treat the patients with stage II if they're at similar risk.  And we pursued KEYNOTE-716 as you mentioned, and it read out last year as a positive trial for recurrence-free survival. And the abstract here then was to look at the impact on distant metastasis-free survival. So, while the regulatory consideration for approval, and it is approved and it's available for patients now, was based on relapse, what we really want to be preventing is the development of metastatic disease because presumably that would correlate with the eventual death of the patient from cancer.  So, in the abstract here, we see the first update for DMFS, which also was positive on its first analysis, the hazard ratio at 0.64. And so, again, very similar to the RFS benefit, showing about a 35-36% reduction in distant metastasis-free survival. And this is a theme that we've seen across adjuvant studies in melanoma, all the adjuvant studies in fact, is that the RFS improvement, the relapse-free survival hazard ratio mirrors very closely the distant metastasis-free survival ratio. We saw that again here. I think it just emphasizes that anti-PD-1 immunotherapy is highly effective in melanoma no matter what stage it's in, but rather related to the risk of death for melanoma.  And so this really has a practice changing in the field of melanoma oncology. Patients need to be referred to medical oncology early for discussion around risk stratification and consideration of adjuvant therapy—I think even at the same time that they're having resection of their primary lesion, and it even calls into  question of whether or not we should even fully be doing procedures like sentinel lymph node biopsies any longer, considering we can make the decision to give adjuvant therapy now based on the primary—albeit that's a controversial area of discussion.  And I would just love for this to start to penetrate into other disease settings. We've seen more recently, approval for neoadjuvant therapy in lung cancer and we see in kidney cancer, bladder cancer. We see adjuvant therapy in—I think we're going to see immunotherapy starting to become an important part of the armamentarium in these hard-to-treat cancers, even at the time that perioperatively before or after surgery.  So definitely a major change in the way we're thinking about stratifying patients and emphasizes that you need to get those patients with melanoma in to have that discussion around adjuvant therapy probably at the time of the primary lesion resection.  Dr. Diwakar Davar: And finally, Abstract 2507, single-cell profiling of human heart and blood in patients with checkpoint inhibitor-associated myocarditis. So, this is data from the NGH Group, Dr. Villani and colleagues are presented by Dr. Blum. We know that myocarditis is an uncommon but very serious immune related adverse event (irAE), and here in this particular dataset, this group which has done a lot of underlying work to really uncover the role of certain key phenotypes, cellular phenotypes, in the development of myocarditis it's presenting the data in the context of ICI-related myocarditis. So, what do you think of this data, what do you think of the use of checkpoint inhibitors are now, as you've said, migrated linear in the lifecycle of the patient, what do we need to be thinking about and how does this improve our understanding of both the use of the drug and what we need to be worried about?  Dr. Jason Luke: I think the toxicities of immunotherapy, while, less frequent than, say, chemotherapy, can actually be more disastrous. In the rare patients, we have extreme immune-related adverse events, there is an incidence of actually life-threatening and fatal events. And so, myocarditis, associated with checkpoint blockade, is one of those things that could be seen, and here at ASCO Annual Meeting, we saw a couple of abstracts summarizing the experience from the National Cancer Institute following myocarditis events, and then this abstract in a translational level trying to better understand what is actually going on in terms of the immune response in those myocarditis cases.  And so, I thought this was actually a very interesting abstract. There was only a small number of patients. They had 13 samples from patients who had had endomyocardial biopsies in the context of immune-related myocarditis, and you might say, well, only 13 samples, but fortunately, this is quite a rare event, less than 1% of patients who get immune checkpoint inhibitors. And what they saw was relatively unsurprising, which is that in patients who were having myocarditis, they saw an increase in T cells and in K-cells, as well as activated CD8 and CD4 T-cells.  I think what was very interesting was when they started to dig into what were the phenotypes of the cells and what were the pathways that were turned on. Again, it was not especially surprising to see that they saw increased levels of interferon signaling and immune-receptor signaling as well as motility and adhesion, but this really, I think emphasizes that there are potentially interventions beyond just the general immune-suppression approaches that we give. They could be more nuanced but perhaps more efficacious because sadly, patients do pass away when they develop this. And in their cohort of 13 patients, 3 of those patients died. And specifically, in looking in those 3 patients, they actually saw that all 3 patients had a shared T cell cluster. And they can't exactly say what it is exactly yet, but I think it's very interesting to see that because it suggests that there's probably something about the T cell response in those patients that disproportionately triggered a fatal event.  And if we can understand that better, we then may be able to really tailor our interventions in a way that is more useful. Because, frankly, the way these patients usually present is they show up in the emergency room (ER), and they're seen by an ER doctor who thinks they're having acute coronary. They ship them off to the catheterization (cath) lab. They open him up, and then they get in there, and there's nothing going on. There's no plaque. And so now, all of a sudden, everyone is quite confused. And so, if we had better ways to search for that ahead of time to be aware of it, we might have better interventions because usually what happens right at that moment is everybody gets very confused and starts calling the oncologist, and we start slapping on steroids and other immunomodulatory agents, but sometimes it's late.  So, I think this is a great abstract. It's really starting to preliminary give us an idea of what is the actual biology that underpins these terrible events, and we can hope that we can build off that over time hopefully to eventually come up with better predictors and then obviously better interventions to try to avoid these outcomes in a small but real number of patients.  Dr. Diwakar Davar: Excellent. One other point is you and I are both involved in drug development, and as we start thinking of side effects. Side effects are really on the flip side of responses in drug development. So really 1 point to make of this is that when people start developing side effects rather than, as you say, putting your hands up in the air and waving them around, 1 of the things that we should be doing in drug development is possibly biopsying these patients because we could get new PD insights into how these drugs work, why they work, and particularly which sub-populations themselves they work on, particularly in the early-drug development setting when you oftentimes don't have that many responses.  With that, thank you, Jason, for sharing your insights with us today.  Dr. Jason Luke: Thank you.  Dr. Diwakar Davar: And thank you to our listeners for your time today. 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. So, thank you for your attention, and we will sign out.      Disclosures:  Dr. Diwakar Davar:   Honoraria: Merck, Tesaro, Array BioPharma, Immunocore, Instil Bio, Vedanta Biosciences  Consulting or Advisory Role: Instil Bio, Vedanta Biosciences  Consulting or Advisory Role (Immediate family member): Shionogi  Research Funding: Merck, Checkmate Pharmaceuticals, CellSight Technologies, GSK, Merck, Arvus Biosciences, Arcus Biosciences  Research Funding (Inst.): Zucero Therapeutics  Patents, Royalties, Other Intellectual Property: Application No.: 63/124,231 Title: COMPOSITIONS AND METHODS FOR TREATING CANCER Applicant: University of Pittsburgh–Of the Commonwealth System of Higher Education Inventors: Diwakar Davar Filing Date: December 11, 2020 Country: United States MCC Reference: 10504-059PV1 Your Reference: 05545; and Application No.: 63/208,719 Enteric Microbiotype Signatures of Immune-related Adverse Events and Response in Relation to Anti-PD-1 Immunotherapy  Dr. Jason Luke:   Stock and Other Ownership Interests: Actym Therapeutics, Mavu Pharmaceutical , Pyxis, Alphamab Oncology, Tempest Therapeutics, Kanaph Therapeutics, Onc.AI, Arch Oncology, Stipe, NeoTX  Consulting or Advisory Role: Bristol-Myers Squibb, Merck, EMD Serono, Novartis, 7 Hills Pharma, Janssen, Reflexion Medical, Tempest Therapeutics, Alphamab Oncology, Spring Bank, Abbvie, Astellas Pharma, Bayer, Incyte, Mersana, Partner Therapeutics, Synlogic, Eisai, Werewolf, Ribon Therapeutics, Checkmate Pharmaceuticals, CStone Pharmaceuticals, Nektar, Regeneron, Rubius, Tesaro, Xilio, Xencor, Alnylam, Crown Bioscience, Flame Biosciences, Genentech, Kadmon, KSQ Therapeutics, Immunocore, Inzen, Pfizer, Silicon Therapeutics, TRex Bio, Bright Peak, Onc.AI, STipe, Codiak Biosciences, Day One Therapeutics, Endeavor, Gilead Sciences, Hotspot Therapeutics, SERVIER, STINGthera, Synthekine  Research Funding (Inst.): Merck , Bristol-Myers Squibb, Incyte, Corvus Pharmaceuticals, Abbvie, Macrogenics, Xencor, Array BioPharma, Agios, Astellas Pharma , EMD Serono, Immatics, Kadmon, Moderna Therapeutics, Nektar, Spring bank, Trishula, KAHR Medical, Fstar, Genmab, Ikena Oncology, Numab, Replimmune, Rubius Therapeutics, Synlogic, Takeda, Tizona Therapeutics, Inc., BioNTech AG, Scholar Rock, Next Cure  Patents, Royalties, Other Intellectual Property: Serial #15/612,657 (Cancer Immunotherapy), and Serial #PCT/US18/36052 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof)  Travel, Accommodations, Expenses: Bristol-Myers Squibb, Array BioPharma, EMD Serono, Janssen, Merck, Novartis, Reflexion Medical, Mersana, Pyxis, Xilio  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.     

Dr. Ismail Jatoi is chief of the Division of Surgical Oncology and Endocrine Surgery at the University of Texas Health Science Center at San Antonio. Stephen Morrissey, the interviewer, is the Executive Managing Editor of the Journal. I. Jatoi, H. Sung, and A. Jemal. The Emergence of the Racial Disparity in U.S. Breast-Cancer Mortality. N Engl J Med 2022;386:2349-2352.

Dr. Stephen Ansell, of the Mayo Clinic in Minnesota, tells host Dr. John Sweetenham, of the UT Southwestern Harold C. Simmons Comprehensive Cancer Center, about ECHELON-1's compelling overall survival analysis in newly diagnosed Hodgkin lymphoma and key advances in the SHINE, MOMENTUM, and ASCEMBL trials that were featured at the 2022 ASCO Annual Meeting.   TRANSCRIPT Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham, the associate director for Clinical Affairs at UT Southwestern's Harold C. Simmons Comprehensive Cancer Center, and host of the ASCO Daily News Podcast.  My guest today is Dr. Stephen Ansell, a professor and chair of medicine at the Department of Hematology at the Mayo Clinic in Minnesota. Dr. Ansell shares his insights on key advances in hematologic malignancies that were featured at the 2022 ASCO Annual Meeting.  Our full disclosures are available in the show notes and disclosures of all guests on podcasts can be found on our transcripts at asco.org/podcasts.   Stephen, it's great to have you on the podcast today.  Dr. Stephen Ansell: Thanks so much for having me, John.  Dr. John Sweetenham: So, Stephen, I'd like to start with your thoughts on Abstract 7503, which of course is one that you authored, and this is a 6-year follow-up study of the ECHELON-1 trial. This includes a positive overall survival analysis for brentuximab vedotin in newly diagnosed advanced Hodgkin lymphoma. Can you tell us more about this?  Dr. Stephen Ansell: Yeah, sure, John. And you know, as you point out, the thing that's really interesting and unique about this trial is we haven't had a lot of studies in Hodgkin lymphoma that show an overall survival advantage as you well know. Doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy has actually been quite difficult to beat when it's been an overall survival endpoint that one has been looking at.  There have been some other strategies in the past that have been looked at—the escalation of therapies such as escalator BEACOPP, and maybe modification of therapy to minimize toxicity, such as the RATHL trial where bleomycin is dropped out.  In all of these studies, there have been advantages for progression-free survival, but not clearly against ABVD as the standard and overall survival advantage. So, our listeners would probably know that ECHELON-1 was a comparison between brentuximab vedotin ABVD chemotherapy, and ABVD chemotherapy as the standard, showing an initially modified progression-free survival advantage and subsequently a progression-free survival advantage. But now with 6 years of follow-up, an overall survival advantage. And I think that's really what makes this quite unique.  Dr. John Sweetenham: One of the reasons I think many people, myself included, thought that it was going to be a very high bar to show an overall survival difference in this study was simply the fact that treatments to relapsed and refractory Hodgkin lymphoma, in general, have improved really quite substantially, both before and during the conduct of this trial.  Do you have any thoughts on that? Were you surprised? And any thoughts on why we're seeing this in the face of the rapidly evolving treatment landscape in the relapse setting?  Dr. Stephen Ansell: Yeah, I think that's an excellent point. And, John, I think there have been 2 schools of thought, as you know, those that have felt that the first shot was always the best one. And you should go hard right off the bat and others have said, you don't need to give everybody intensive treatment, because as you say, subsequent therapies can be very effective.  This would actually challenge that second position because when we looked at how patients were managed in both groups when they relapsed, the vast majority of relapsing patients in the group that got ABVD subsequently got brentuximab vedotin, as part of their regimen. Most patients—and it was balanced in both arms—got the standard kind of salvage treatment, autologous stem cell transplant approach, and some patients in both arms, got novel agents, including PD1 blockade, that was a minority, partly because of the timing of when the study was done.  But I think all of the things that we would normally do were done, and yet there's still a survival advantage. The one interesting thing I think that's worth taking away from this is when one looked at some of the influences on what might have made that overall survival difference, there were more patients progressing and dying from Hodgkin's in the ABVD arm suggesting that adding brentuximab vedotin does make a difference to the disease itself. But also interestingly, there were fewer patients in the brentuximab arm, who got a second lymphoma.  And interestingly, there were quite a substantial number of people in the ABVD arm when they relapsed to or subsequently got a different lymphoma, suggesting that the brentuximab vedotin, may actually target a precursor cell in a heme malignancies space and actually may have a benefit that way.  Dr. John Sweetenham: So, what's your overall conclusion from this study now that brentuximab vedotin plus ABVD is the standard of care for patients with newly diagnosed advanced Hodgkin lymphoma?  Dr. Stephen Ansell: I would say that if you have advanced-stage disease with classical Hodgkin lymphoma histology, it's very difficult not to say that this would be the standard of care to manage the patients.  I think we've learned that this study applied to older patients who are often difficult to treat. And so, hence, that's also a very valid treatment to give. And it's very difficult to argue against giving treatment that has an overall survival advantage for patients. So, in my practice, this has become the standard of care.  Dr. John Sweetenham: Okay, great. Thanks, Stephen. Let's move on and talk about LBA7502. This reported on the primary results of a double-blind placebo-controlled study known as SHINE, which looks at the use of ibrutinib in combination with bendamustine and rituximab followed by rituximab maintenance as a first-line treatment for older patients with mantle cell lymphoma. What are your thoughts and key takeaways from this study?  Dr. Stephen Ansell: Again, I think this is a very important study in older patients with mantle cell lymphoma. So, as you well know and many of our listening audience would know that we kind of has 2 strategies in mantle cell lymphoma. In younger patients, we may treat them with a more intense approach, sometimes with autologous stem cell transplant, often with a kind of alternating high-intensity therapies.  For patients who are older, bendamustine rituximab is really a standard therapy for patients with that demographic. And this now really pushes the field forward by showing that if you take bendamustine rituximab and add ibrutinib an effective therapy in the relapse setting, in the upfront setting, there is a substantial advantage for how patients do.  If one looks at the overall outcomes, it shows that progression-free survival is improved; we don't have overall survival benefit yet. But as we track these patients, it'll be interesting to see if that does transpire in time.  I will say again that I always like placebo-controlled arms because it helps us really get a handle on toxicities. And in general, in this population of patients, it was well tolerated. So, I think this, again, is a regimen that is going to be very useful in older patients.  Dr. John Sweetenham: I think that the lack of an overall survival benefit so far could of course be because there was a crossover in a study for those patients who progressed on the placebo-controlled arm.  But my other question about this, just to get your impression, is that there is a subgroup of elderly patients or older patients with a very slowly progressive disease where the management approach has been more of a watch-and-wait and observation-only approach until they become symptomatic. Do you think results like this, which start to show a progression-free survival benefit from upfront therapy, change that philosophy? Should we be thinking harder about whether anyone should be observed now?  Dr. Stephen Ansell: I think that's a good question. And to be frank, I will say that in my practice, I still have a spirit of, I'm happy to watch patients who have a very low burden of disease to just get a sense of the pace of the disease. Because as you say, you may be surprised by a subset of patients whom you may not need to treat for a year or even longer. And my view is that a year of no treatment is always better than a prolonged progression-free survival interval on treatment. So, I take the view that if you don't need to treat, that is still the best management.  Dr. John Sweetenham: Great, thank you! So, we're going to change gear for a moment and move out of lymphoid malignancy and talk a little about Myeloproliferative Syndrome. I'm interested to hear your thoughts on the MOMENTUM study. So, this was Abstract 7002, another phase 3 randomized study, in this case, looking at the use of momelotinib versus danazol in symptomatic and anemic patients with Myelofibrosis, who previously had a JAK inhibitor. What are your thoughts on this study?  Dr. Stephen Ansell: I think again, this is really good and very interesting data because those that treat Myelofibrosis will know these are challenging to treat. And many times, the symptoms they experience, the transfusion challenges they have, and the difficulty they have with very large spleens are all things that impact the quality of life quite profoundly. And therapies, in general, that would benefit those symptoms are always highly valuable.  So, I did find, again, I'm not as much of an expert in Myelofibrosis, but certainly, my colleagues who are were very satisfied with these results, basically showing improvement when compared to danazol, which again, I would anticipate as modest control with not particularly good efficacy, again, some of those symptoms I just spoke about, but momelotinib really showed a substantial benefit for the symptoms that this disease causes, and obviously transfusion requirements and improved spleen sizes and spleen symptoms.  So, I think in general, for managing patients for whom the quality of life is profoundly impacted, this is going to be a useful agent moving forward.  Dr. John Sweetenham: Okay, great. Thanks. And staying on the theme of Myeloid diseases, Abstract 7004 reported on the efficacy and safety, from the so-called ASCEMBL study, another phase 3 study, in this case, looking at the use of asciminib versus bosutinib in patients with Chronic Myeloid Leukemia (CML) who are in chronic phase, and who had already received 2 or more tyrosine kinase inhibitors. And this was an update at week 56 of the study. Why do you think this study should be on our radar?  Dr. Stephen Ansell: Well, I think again, we're always looking for agents that make a difference, particularly with subsequent lines of therapy in this disease. I think bosutinib is really regarded as a standard of care in this population of patients and an agent that comes along, ascitinib in this case, that shows a significant benefit, that really brings yet another tool for us to utilize in these patients.  I must say, again, as I looked at the results, comparing also looking for the major molecular responses, and the benefit and durability thereof, this was pretty impressive data. And so, I think it's very useful in this disease to have a plethora of tools that we can reach to be able to really impact the outcome of patients. So, I think, again, this is highly relevant data that we would use in the clinic in the not-distant future.  Dr. John Sweetenham: Do you think it's likely it'll move into frontline treatment over time?  Dr. Stephen Ansell: So, I think that is a good question. I don't know the answer to that, except to say that these results are pretty impressive. And so, I do believe that that's going to need to be tested, but as has been done in CML over the decades and which is really to be applauded, there have been randomized trials, comparing head-to-head agents showing which agent really has the greatest benefit and efficacy. So, I'll watch that space with a lot of interest.  Dr. John Sweetenham: Thanks! And finally, I'd like to return to lymphoid malignancy. In the 2020s, it would be almost impossible to review a meeting such as ASCO without saying something about CAR T-cell therapy, and this podcast is going to be no exception.  So, I wonder if I could get your thoughts on Abstract 7571. And this was an abstract, which reported real-world outcomes for axicabtagene ciloleucel, otherwise known as the Axi-Cel, for the treatment of large B-cell lymphoma. And it looked at the outcomes according to race and ethnicity. What are your thoughts on this study?  Dr. Stephen Ansell: Well, John, I smiled when you were said there's not a possible to really have a conversation without bringing in CAR T-cell somewhere along the way, but what I liked about this abstract, is it really was bringing in the real-world data, because many times and again, I have to stress that real-world data, when it comes to CAR T-cells is probably not the real world in the most real-world nature of things. And that is just you have to have access to certain centers to be able to get this therapy. And I think that's what this abstract actually points to.  It does look at almost 1,400 patients treated with Axi-Cel. And now that in large cell lymphoma, this is a standard of care where we either use a post-transplant and now even as a first relapse therapy, this is becoming highly relevant. And the question is just always seeing discrepancies between various population groups when we look at how outcomes transpire from this therapy.  And as it turns out, if one looks at Asian populations, those are really not adversely impacted, or Hispanic populations. But the African American population continues to have a less favorable outcome, even with this sophisticated therapy.  And that does suggest that possibly, when those patients, in general, can get access to this care, might actually be a little later in the disease, greater disease burden, possibly a little later line of therapy, resulting in not as favorable results.  I think this is whereas health care providers, we need to turn our attention in the future. And that is to say, how can we make care be equally good for all patients everywhere within our country, rather than there being nuggets where certain people benefit a lot and other areas where people benefit very little.  Dr. John Sweetenham: Yeah, thank you. There was good discussion after this study was presented and I think much of it focused around exactly what you've just said. Most of this difference is almost certainly not biological but it's really related to access to care and so on and that was an important take-home message. So, thanks for emphasizing that.  Stephen, thanks so much for sharing your insights with us today regarding the 2022 ASCO Annual Meeting on our podcast. I really appreciate your being willing to talk to us.  Dr. Stephen Ansell: John, thank you very much for having me.  Dr. John Sweetenham: And thank you to our listeners for joining us today. You'll find links to the abstract discussed today on the transcripts 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.    Disclosures:  Dr. John Sweetenham:  Consulting or Advisory Role: EMA Wellness  Dr. Stephen Ansell:  Honoraria: WebMD, Research to Practice  Research Funding (Inst.): Bristol-Myers Squibb, Seattle Genetics, Affimed Therapeutics, Regeneron, Trillium Therapeutics, AI Therapeutics, ADC Therapeutics  Disclaimer:  The purpose of this podcast is to educate and inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.   Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity or therapy should not be construed as an ASCO endorsement.       

Lies and Exaggerations about Kids Vaccine I give examples, and show why they are lies

In part one, of this two-part ASCO Education podcast episode, host Dr. Jeremy Cetnar (Oregon Health & Science University) interviews two very accomplished physicians and researchers, Dr. Lauren Abrey and Dr. Jason Faris. We'll hear about their motivations for pursuing medicine and how they arrived at the different positions they've held in academia and industry.  If you liked this episode, please subscribe. Learn more at https://education.asco.org, or email us at education@asco.org.   TRANSCRIPT   Dr. Jeremy Cetnar: Hello, and welcome to the ASCO Education podcast episode on career paths and oncology. My name is Jeremy Cetnar. I'm a Medical Oncologist and Associate Professor of Medicine at Oregon Health and Science University in Portland. I'm delighted to introduce today's two guests, whose careers in oncology have crisscrossed academia and industry. Dr. Lauren Abrey and Dr. Jason Faris, I'm excited to chat with you about the inspiration and motivations that drive you, people you've leaned on, how you've made your career decisions, challenges you've faced, and more.  So let's start by asking each of you, could you share a little bit about your early life and background, what attracted you to medicine, and who are some of your early mentors and role models? Let's start with you, Dr. Faris.  Dr. Jason Faris: Yeah, I'd be happy to. Thank you. So, I grew up in a small town in South Jersey in Greater Philadelphia. My mom was a registered nurse in pediatrics in the maternal infant unit for many years at Cooper Hospital. I was always interested in science and medicine and my mom's dedication to her patients. Her altruism and compassion served as a real inspiration for me, for my eventual decision to go to medical school. But I took a long time to get there. I had a bit of a circuitous route to arrive to my career in medicine though it started off conventionally enough. I was initially geared towards a premedical track in college, majoring in biology, but an exciting summer research project, working on the biochemical mechanisms underlying osmoregulation in a marine crustacean with mentoring from my first true mentor, Dr. Don Lovett, led me to apply to and attend graduate school in molecular biology at Princeton.  This was followed by a position at Merck as a molecular biologist in the genetic and cellular toxicology group. I went to veterinary school at the University of Pennsylvania where I met my future wife. And then finally, back to the original plan of attending medical school, but I have to say with a much better sense of why I wanted to attend medical school in the first place, now in my late 20s, which was a bit unconventional at the time. I really did my fair share of exploration of Allied Health careers. That's for sure. I attended Johns Hopkins for medical school, where I quickly discovered a passion for internal medicine. And that was far and away my favorite clerkship and sub-internship. That's the background to how I got to medical school.  Dr. Jeremy Cetnar: Dr. Abrey?  Dr. Lauren Abrey: Interesting. I love your story. We share... I grew up in a small town, not so far away, but I was in upstate New York. And I think there were two influences that kind of got me to my ultimate passion for brain tumors. And this sounds a little quirky to start with. But I had a pretty serious head injury as a tween. So I guess I was about 12. I had a skull fracture, epidural hematoma. And while I would never have said I woke up at that moment and thought I have to be a doctor, I think I became fascinated about things to do with the brain.  In parallel, something that I think tinged a lot of my childhood was a number of family members who had cancer. So both of my grandmothers had breast cancer, while I was well aware of the fact that they were sick and battling this. And two of my aunts also had cancer. And I would say it's an interesting split in my family. So about half of them are survivors and about half ultimately died of their disease.  So both of these things really motivated me or focused me on the need to do something important, but also to do something that really motivated me to get out of bed in the morning. I think I was much more to the point. I went straight to college, straight to medical school. I remember calling my parents and telling them I was applying to medical school and having them say, “Wait. You? Really?” So it wasn't necessarily the family expectation that I would do this, but I was very driven and motivated to make some of these choices and then discover my particular interests as I progressed through medical school. So I went to Georgetown for medical school and then have trained at a number of places in the US. I think that's a little bit how I took my first step on this career journey, let's say.  Dr. Jeremy Cetnar: So take us through what the decisions were like in your head at the end of fellowship in terms of first jobs. Dr. Faris?  Dr. Jason Faris: In terms of my choice to pursue a career in medical oncology, this goes back to medical school during an internal medicine clerkship. I had an assistant chief of service, ACS, at the time, Phil Nivatpumin. He'd go on to become a medical oncologist. He really inspired me with his optimism and bedside manner, including with multiple oncology patients on that clerkship. His enthusiasm for science and medicine, his teaching skills, and an absolutely legendary fund of knowledge. For Phil, he was just an incredible ambassador for both internal medicine and for oncology.  After medical school, I went to internship and residency at Mass General Hospital. And in one of my first rotations, I was on the oncology service, which was not so creatively called Team Three. I think they can up the ante there, but oncology services on Team Three. I was caring for many extremely ill patients battling disease progression from their metastatic cancers, or sadly, in many cases complications of their treatments. During that rotation, I was intrigued by clinical trials offering novel treatment options based on cutting edge science, but also struck by the number of patients who just didn't have any clinical trial options. I became aware of the limitations of the conventional treatments that were offered.  I was really inspired by the patience and dedication of the nurses and doctors caring for them. And I vividly recall a roughly 50-year-old woman I helped care for with AML, watching as the 7+3 chemotherapy caused lots of side effects for her and being amazed by her strength and grace, her resilience as she faced her illness, her potential mortality, and the intense chemotherapy she was undergoing. And I knew during those moments with that leukemia patient while caring for other patients on that oncology service that this was the field I would pursue. Oncology was really the perfect blend of humanism, problem solving, longitudinal follow-up and rapidly accelerating scientific progress leading to new avenues for clinical trial treatments.  Like Lauren, I was motivated and inspired by cancer diagnoses in my own family. My maternal grandmother died of pancreatic cancer during my junior year of college. My dad was diagnosed with colon cancer during my first year of fellowship. So those are all really strong motivators, I would say. And after completing my fellowship at the combined Dana-Farber MGH program, my first position out of fellowship was in the gastrointestinal cancer group at MGH. I actually had been training in genitourinary oncology after my main clinically focused year of fellowship, but I did a chief resident year in the middle of fellowship, and that was the tradition at MGH. And as I was about to return to fellowship for my senior year of fellowship, the head of the GI Group and head of the Cancer Center at the time, Dave Ryan, offered to serve as a clinical research mentor for me in GI cancers. As a senior fellow, I wrote an investigator-initiated trial of cabozantinib for patients with neuroendocrine tumors under his mentorship that went on to demonstrate encouraging results, led to a Phase III study in that cancer population, and I ultimately accepted a position at the MGH Cancer Center in the GI cancer group about 11 years ago. And that was the start of my post-training career.  Dr. Jeremy Cetnar: And how about you, Dr. Abrey?  Dr. Lauren Abrey: So for people who don't know, I'm actually a neurologist. I finished my training in neurology and then pursued a fellowship in neuro oncology. I would say it was really patients and observations of things that were happening with patients during my residency. I did my residency at the University of Southern California at Los Angeles. I was at the LA County Hospital, which for people who don't know, is one of the largest hospitals in the country. I had the chance to see several patients who had paraneoplastic syndromes, and got the support from different faculty members to write those cases up, and really resulting in my first independent publications. That was what kind of got me bitten by the bug to understand this link between neurology and oncology.  I very intentionally went to Memorial Sloan Kettering to have the opportunity to work with Jerry Posner. And I think I no sooner got there than I got totally bitten by the brain tumor bug, which seems a little counterintuitive. But the paraneoplastic work was kind of deep laboratory work. And I realized that I really enjoyed seeing the patients having the partnership with neurosurgeons and digging into what is still a pretty intense unmet medical need.  So it was an interesting pivot because I really thought I was going to Sloane to focus on paraneoplasia. I still think I learned so much with that interest that I think we can reflect on when we consider how immunology has finally entered into the treatment landscape today for different tumor types and understanding is there a background in paraneoplastic disorders that could help us. But I have to say it was really the brain tumor work that got me focused and the chance to work with people like Lisa DeAngelis, Phil Gutin, and others that was kind of fundamental to my choices. I stayed there for two years of fellowship and then continued as faculty for about another 15 years at Sloan Kettering. So that's really the start of my academic career and the pivot to industry came much later.  Dr. Jeremy Cetnar: So both of you have impressive career CVs, have been trained at very prestigious institutions. So at some point in time, take me through, what was that transition like between, 'Hmm, what I'm doing is enjoyable, but maybe there's something else out there that I want to explore.' And what I mean by that is mostly industry at this point. So that's an important question that I think a lot of junior faculty face, a lot of mid-career faculty, maybe even later-stage faculty. But I think that's a tension point for a lot of people because I think there's a lot of fear. I think there's a lot of anxiety about moving outside of the academic realm. So, tell us a little bit about what was the pull in terms of going to industry and what were some of the thought processes that were going on. Dr. Faris?    Dr. Jason Faris: I've experienced two transitions, actually, between academia and industry. I like to do things in pairs, I guess. But the first was, after multiple years at the MGH as a resident fellow and as a clinical investigator at the MGH Cancer Center. As a new attending and clinical investigator, I was attempting to balance my work priorities, providing patients with GI cancers, which is a rewarding but complex and I'd say emotionally intense experience, given the phenomenally aggressive and devastating cancers these patients grapple with such as pancreatic cancer, alongside the other responsibilities of my clinical investigator position.  Those other responsibilities included writing grants and papers and protocols, evaluating patients who were interested in open clinical trials, and serving as the principal investigator for multiple studies. I was serving on committees, mentoring and teaching. Patient care was always my top priority as it should and really must be. And I feel incredibly lucky to have had truly amazing colleagues at MGH across several disciplines, from medical oncology, nurse practitioners, practice nurses, radiation oncologists, and surgeons. It was and continues to be a dynamic place full of extremely talented and dedicated clinicians. I think we really all benefited from the coordinated teamwork in both patient care and research in a really tight-knit GI Group.  But nonetheless, for me as someone who delighted in spending large amounts of time with my patients in the clinic rooms, and I think my colleagues would agree frequently agonizing over decisions impacting their care, achieving sufficient balance to really focus on writing and overseeing clinical trials was becoming increasingly challenging for me. And it was in that context, after spending roughly a decade and the combination of residency fellowship training and as an attending in the GI cancer group all at MGH that I made a truly difficult decision to move from my beloved outpatient clinical and clinical investigator role to industry to focus more exclusively on clinical research.  And after interviewing for several industry-based roles, I accepted a position in the early-phase group at the Novartis Institutes for Biomedical Research or NIBR as we kind of pronounced those words in Cambridge. I absolutely loved my time at NIBR. It's an incredible place with a strong history of and commitment to innovation as well as passionate, talented colleagues, many of whom I've worked with in the past. When I first started at Novartis, I was amazed at the array of experts on the teams I was helping to lead as a clinical program leader. Our teams are the definition of multidisciplinary. They're composed of what we call line function experts in multiple disciplines. This includes preclinical safety experts who design and analyze data from studies that precede the filing of an IND, research scientists, chemists, preclinical, and clinical pharmacologists, statisticians, program managers, drug and regulatory affair colleagues, who focus on the interactions with health authorities, including the FDA, operational colleagues called clinical trial leaders, and many others.  In my role as a senior clinical program leader, I also have the opportunity to collaborate frequently with research colleagues on preclinical programs, designing and writing first in human trials, followed by conducting the actual studies and in close collaboration with our academic colleagues, analyzing the clinical and translational results.  Dr. Jeremy Cetnar: Dr. Abrey, how about you? Was there a moment or what were the moments that led to you deciding to make this transition?  Dr. Lauren Abrey: I guess I have the other sort of story. I got pushed, I would say, in the sense that like many of us, I'm married, and my husband was the one who took a job with Novartis and said, “This would be an adventure. Let's go live in Switzerland.” So similar to Jason, he took a position at NIBR, and I think for many of the same reasons, he really wanted to delve deeply into early mechanism of action and allow himself to dedicate really a chunk of his career to developing key drugs. But moving to Switzerland changes your options suddenly. I think I had spent most of my career at Sloan Kettering doing clinical trials. That was really my comfort zone, my sweet spot. And when we moved over here, I explored briefly, could I set up an academic career here?  And very kindly, I was invited by a number of Swiss colleagues to look for opportunities to do that. But I realized what I loved was talking to patients, and that that was going to be difficult with the language barrier. And I equally loved running clinical trials. So I had a great opportunity to join Roche shortly after their merge or full acquisition of Genentech. This allowed me to continue the work I had been doing on Avastin for brain tumors.  But I think the other thing that allowed me to do, that was something I was really looking for was to broaden my scope and to no longer be niched as just a brain tumor expert. And if you're in academia and you're a neurologist, obviously, you're going to be fairly constrained in that space. But moving into a role in industry really allows you to look much more broadly and work across multiple tumor types. And I spent the next seven years at Roche running not just the Avastin teams that were developing drugs for a number of indications, but really overseeing the clinical development group based in the European sites. And they had about 14 different drugs in different stages of development as well as partnerships with their early research group that was European based.  So it was a fascinating time for me, and I feel kind of like I got thrown into the pond. I knew a lot about clinical trials. I had no idea about so many other aspects of what I needed to consider. And I think Jason started to allude to some of this with the different line function expertise and things I think we take for granted or maybe we simply have blind spots around them when we are sitting in our academic organizations. So it's been a really delightful plunge into the pool. I've continued to swim mostly. Occasionally, a little bit of drowning, but a lot of fun.  Dr. Jeremy Cetnar: What would you say are the major differences between an academic career and industry?  Dr. Lauren Abrey: I think, as you said, the things that are similar is that the purpose or the mission for both is in many ways the same. We would like to develop better treatments for patients with cancer. And so there's a huge focus on clinical trials. There needs to be a huge focus on patients, and that can get diluted in industry. I think the things that you don't appreciate sometimes when you're sitting on the academic side is just really the overarching business structure and the complexity of some of the very large organizations. So you suddenly are in this huge space with people focused on regulatory approvals focused on pricing, focused on manufacturing, focused on the clinical trial execution, and why you are doing it in different spots.  And so I think some of the different factors that you have to consider are things that again, we either take for granted or are super focused when you're in one organization. And I think the tradeoffs and how decisions are made, particularly in large pharma, can be frustrating. I think we are all used to applying for grants or getting the funding we need to do whatever our project or trial is. And then you just start very laser focused on getting to the end. If you're in a large organization and they have a portfolio where they're developing 14, 15, 20 different things, you might suddenly find that the project you think is most important gets de-prioritized against something that the company thinks is more critical to move forward. And that could be because there's better data, but it could also be because there's increasing competition in the space or there's a different pull for a large company. I haven't seen the early development side as much. I've seen the development. I've now seen Medical Affairs for how some of those decisions are made, but I'd be curious to hear what Jason has seen in some of his experiences as well.  Dr. Jason Faris: Comparing and contrasting a little bit between the two, because I've run early phase studies on the academic side, I'll talk more about that in a little bit in terms of another academic position that I held. So I've run early-phase studies there. I've run early-phase studies in industry as well. And they share a lot of similarities, certainly following compelling science, the excitement about new therapies that are going to be offered to patients. But I think the execution is a bit different, and I would say, when you're running clinical trials in the academic setting, you're meeting every patient that you're going to put on study or at least one of your colleagues is, if you have sub-eyes on the study, that's a major, major difference, right? You're directly taking care of a patient going on to an experimental therapy, consenting that patient, following them over time, getting the firsthand experience and data from that patient interaction, but not necessarily, unless you're running an investigator-initiated study, not necessarily having access to the data across the whole study.  You're hearing about the data across the whole study at certain time points on investigator calls, PI meetings, dose escalation meetings, those kinds of things. But you're not necessarily having access to the real-time emergence of data across the whole study from other people's patients. So you're a bit dependent on the sponsor to provide those glimpses of the data, synthesize that and present overview. So those are some operational differences, I would say, because you're not taking direct care of the patients and having your time split among different commitments in that way I have felt a greater ability to focus on the clinical research that I'm doing in my industry-based role, which I like, of course, but I also miss taking care of patients. I love taking care of patients.   So I think it's always a double-edged sword with that if we can use a sword analogy here. But I think they both offer really exciting options to pursue new therapies for patients, which for me, was one of the fundamental reasons that I pursued medical oncology in the first place. It was really this idea that the field is rapidly advancing. I wanted to be a part of that. I saw firsthand what cancer could do to my family or family members, and I took care of patients in the hospital as an intern resident and fellow where I think there's just a tremendous unmet medical need. And so having an opportunity to contribute to the development of new therapies was always a real inspiration for me.  Dr. Jeremy Cetnar: With that being said, what led you to go back into academia?  Dr. Jason Faris: This is an ongoing saga, I guess. So after several years of professional growth at Novartis, gaining experience with designing and conducting clinical trials on the industry side, I was actually at ASCO and I learned of an open role for the director of the early phase trials program at Dartmouth's Cancer Center. After extensive consideration, which I think you can see as my trademark at this point, I made another difficult decision to interview for the position, which was focused on helping to grow the early phase trials program at an NCI comprehensive designated cancer center that's unique in a way because it's in a rural area. And it had a new director of the Cancer Center, Steve Leach, who's a renowned laboratory scientist with a focus on pancreatic cancer and a surgeon by training.  I ultimately decided to accept the early phase director position, moving my family away from Greater Boston, where we had lived for about 15 years, to the upper valley of New Hampshire. And while at Dartmouth, I was part of exciting projects, including writing and overseeing an NCI grant called Catch Up, which was geared towards improving access to early phase clinical trials for rural patients. I opened numerous sponsor-initiated immunotherapy and targeted therapy, early phase trials. Just to say a little bit about Dartmouth's Cancer Center - I think they also benefit from tremendous collaboration, this time across Dartmouth College, the Geisel School of Medicine, the School of Public Health. I think they provide really excellent care to their cancer patients. And I was extremely proud to be part of that culture in the GI Group, which was much smaller than the one at MGH, but also an incredibly dedicated group of multidisciplinary colleagues who work tirelessly to care for their patients.  But nonetheless, less than six months into that new position, the COVID pandemic started, and that introduced some significant and new challenges on the clinical trials side in terms of staffing, infrastructure, those kinds of things. In that context, I made a decision to return to NIBR, refocus on clinical research, and hope to harness my background in running clinical trials in both settings, both academic and industry, as well as the resources and pipeline of Novartis to really maximize my impact on drug development. So for me, it was a question of where can I have the maximum impact at this crazy time, difficult time. I saw that my best option was to return to industry to work on studies to try to develop new therapies. Broadly speaking, my role as a senior clinical program leader in the translational and clinical oncology group at NIBR is to design, write, conduct, and analyze innovative clinical trials of early phase therapeutics.  Dr. Jeremy Cetnar: Wow, that's fascinating, very, very interesting. A lot of stress. You should definitely be buying lots of presents for your family for moving them all over the place.  This concludes part one of our interview with Drs. Abrey and Faris. Thank you so much for sharing your inspiring career stories. And thank you to all our listeners for tuning into this episode of the ASCO Education Cancer Topics podcast.  Thank you for listening to the ASCO Education podcast. To stay up to date with the latest episodes, please click subscribe. Let us know what you think by leaving a review. For more information, visit the Comprehensive Education Center at education.asco.org.    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. 

At the ASCO 2022 Annual Meeting, Oncology Times reporter Peter Goodwin interviewed Marla Lipsyc-Sharf, MD, Medical Oncology Fellow at Dana-Farber Cancer Institute/Mass General Brigham, who reported what she believes is the first data on ctDNA detection in late adjuvant, hormone receptor-positive breast cancer. The research showed ctDNA testing was successful in detecting measurable residual disease (MRD) prior to late clinical metastatic recurrence in women with high-risk, HR-positive, HER2-negative breast cancer (Abstract 103).