ASCO Daily News American Society of Clinical Oncology (ASCO)

Doctors James Ferriss, Linda Duska, and Jayanthi Lea discuss the promise and the challenges of targeting the immune system with immune checkpoint inhibitors, or ICIs, in cervical and endometrial cancers. They also examine emerging data that support the use of ICIs in recurrent cervical cancer, the potential for curing some patients with advanced endometrial cancer, and molecular factors that make cervical cancer a good target for immunotherapy.
TRANSCRIPT
Dr. James Stuart Ferriss: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. James Stuart Ferriss, your guest host of the ASCO Daily News Podcast today. I'm an associate professor of gynecology and obstetrics and the Gynecologic Oncology Fellowship Program Director at Johns Hopkins Medicine. In today’s episode, we'll be discussing the use of immunotherapy in cervical and endometrial cancers to advance the treatment of these malignancies. I'm delighted to be joined by two acclaimed experts in this space, Dr. Linda Duska and Dr. Jaya Lea.  
Dr. Duska is a professor of obstetrics and gynecology and serves as the associate dean for clinical research at the University of Virginia School of Medicine. Dr. Lea is a professor of obstetrics and gynecology and chief of gynecologic oncology at the University of Texas Southwestern Medical Center. 
Our full disclosures are available in the transcript of this episode, and disclosures related to all episodes of the podcast are available at asco.org/DNpod. Drs. Duska and Dr. Lea, it's great to have you on the podcast today. 
Dr. Linda Duska: Thanks, Dr. Ferriss. 
Dr. Jayanthi Lea: Thanks, Dr. Ferriss. 
Dr. James Stuart Ferriss: So, let's get started. In recent years, we've had a revolution in the treatment of advanced endometrial and cervical cancers with improved outcomes for patients treated with immunotherapy. And when we say immunotherapy, we're specifically talking about immune checkpoint inhibitors today. A few of these agents have actually been approved in the United States for the management of these diseases. In our discussion, I'd like to review the promise and challenges of targeting the immune system in patients with advanced endometrial and cervical cancers, as well as review the most recent evidence we have in these spaces. 
Let's start with cervix. We've had a lot of improvements in outcomes here, Dr. Lea, and with cervical cancer, we've seen improved overall survival with the incorporation of immunotherapy along with chemotherapy and anti-angiogenic therapy for advanced and recurrent disease. Can you remind us why cervical cancer is a good target for immunotherapy? 
Dr. Jayanthi Lea: Yes, Dr. Ferriss. Immunotherapy for cervical cancer is supported by several molecular factors. And I think first and foremost, it's so important to remember that the majority of cervical cancers are HPV-positive. And HPV-positive cancers can induce a high level of inflammation, but this high level of inflammation actually contributes to evasion of immune surveillance. What it also does is that it’s responsible for the induction of PD-L1. And we've seen several studies that have shown that cervical cancers express PD-L1 anywhere from 50 to 90 percent of cases. Other pertinent factors to consider are that cervical cancer can be considered a tumor with a high tumor mutational burden. So, the number of somatic mutations that we see in the DNA can be considered as a proxy for neoantigens. And so the higher the level of neoantigens, the more immunogenic the tumor. And then lastly, about 1 in 10 cervical cancers present with microsatellite instability, which is an already established key biomarker for the response team in care. 
Dr. James Stuart Ferriss: So, thinking about targeting PD-L1, what clinical evidence do we have that supports the use of immune checkpoint inhibitors in recurrent cervical cancer? 
Dr. Jayanthi Lea: We now have several studies that have shown a benefit for immune checkpoint inhibi

Drs. Shaalan Beg and Aparna Parikh discuss the role of ctDNA as a powerful prognostic biomarker for GI cancers, along with its impact on risk stratification and the detection of recurrence. They highlight key studies in ctDNA that were featured at the 2024 ASCO GI Cancers Symposium, including COBRA, GALAXY, and BESPOKE in CRC, as well as the promise of ctDNA testing in the preoperative detection of iCCA.
TRANSCRIPT
Dr. Shaalan Beg: Hello, and welcome to the ASCO Daily News Podcast. I am Dr. Shaalan Beg, your guest host for the ASCO Daily News Podcast today. I am an adjunct associate professor at UT Southwestern's Harold Simmons Comprehensive Cancer Center in Dallas. On today's episode, we will be discussing the emergence of circulating tumor DNA (ctDNA) technology in GI cancers. I am delighted to be joined by Dr. Aparna Parikh, an assistant professor of medicine at Harvard University and the director for colorectal medical oncology at the Massachusetts General Hospital Cancer Center, where she also serves as the medical director of the Young Adult Colorectal Cancer Center. Dr. Parikh will share her insights on key research on this hot topic in GI oncology that was featured at the recent ASCO Gastrointestinal Cancers Symposium. 
Our full disclosures are available in the transcripts of this episode, and disclosures related to all episodes of the podcast are available at asco.org/DNpod. 
Dr. Parikh, it's great to have you on the podcast today.
Dr. Aparna Parikh: Thanks so much, Dr. Beg. 
Dr. Shaalan Beg: In recent years, it has become evident that liquid biopsy and other emerging ctDNA technologies are changing how we treat GI cancers, and colorectal cancer (CRC) is in the forefront of this space. Before we dive into key studies, can you briefly highlight for our listeners how ctDNA is advancing the field and how it can influence the care that we deliver to our patients in the future?
Dr. Aparna Parikh: Absolutely, ctDNA is certainly a hot topic. What we have learned over the years is that ctDNA has emerged across many solid tumor types as one of the most powerful, if not the most powerful, prognostic biomarker we have to date. ctDNA has improved risk stratification. We have learned a lot about the role in what is called minimal or molecular residual disease in patients with early-stage disease, and ctDNA being a biomarker of recurrence for those patients, with ctDNA, we have a better understanding of tumoral heterogeneity, both spatially and temporally, getting a better glimpse of what is happening in a given patient with multiple metastases, as well as genomic evolution of tumors over time. So certainly many, many roles and areas where ctDNA is emerging.
Dr. Shaalan Beg: This was a hot topic at the 2024 ASCO GI Cancers Symposium, and we're going to take a deep dive into some of the abstracts that were presented. Let's start with the COBRA study, which is the NRG-GI005. That was Abstract 5 at the ASCO GI Cancers Symposium, and the GALAXY study, which was Abstract 6 at the symposium. So, the COBRA study reported results of ctDNA as a predictive biomarker in adjuvant chemotherapy for people with colon cancer. At a high level, it was a negative study, but there are some important lessons for us to learn. Similarly, in the GALAXY study, investigators from Japan presented an updated analysis on the correlation of ctDNA dynamics with outcomes in colorectal cancer with minimal residual disease. How do you synthesize all this information and help the listeners understand our current state for ctDNA applications in colorectal cancer?
Dr. Aparna Parikh: Yeah. Let's take the COBRA study first. Let's talk a little bit about the design of COBRA. COBRA was intended to look at patients that were resected, stage 2 colorectal cancer patients, or colon cancer patients who were 2A. These are patients where the treating physician would, at the outset, decide that there was no adjuvant chemotherapy indicated. These are

Drs. Shaalan Beg and Travis Osterman discuss a machine learning model, recently featured in JCO Clinical Cancer Informatics, that uses electronic health record data to accurately predict the effectiveness and toxicity of treatment with immune checkpoint inhibitors. The new AI model can be used to provide a personalized risk-benefit profile, inform therapeutic decision-making, and improve clinical trial cohort selection.
 
TRANSCRIPT
Dr. Shaalan Beg: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Shaalan Beg, your guest host for today. I am an adjunct associate professor at UT Southwestern's Simmons Comprehensive Cancer Center. 
Cancer immunotherapy has transformed the treatment landscape by providing new and effective treatment options for many solid and hematologic malignancies. But while many patients experience a remarkable response to immune checkpoint inhibitors, other patients can suffer life-threatening immune checkpoint toxicities. Today, we will be discussing a machine learning solution that can assess a patient's immune checkpoint inhibitor risk-benefit profile based primarily on routinely collected structured electronic health record data. This novel AI solution was recently featured in JCO Clinical Cancer Informatics, and I am delighted to welcome one of the report's authors, Dr. Travis Osterman. He is an associate vice president for research informatics and associate professor in the Department of Biomedical Informatics and the Division of Hematology Oncology at Vanderbilt University Medical Center in Nashville, Tennessee. Dr. Osterman also serves as the director of cancer clinical informatics at the Vanderbilt Ingram Cancer Center. 
Our full disclosures are available in the transcript of this episode, and disclosures related to all episodes of the podcast are available at asco.org/DNpod. 
Dr. Osterman, it's great to have you on the podcast today.
 
Dr. Travis Osterman: Thanks, Shaalan. It's great to be here. Thank you for the invitation.
 
Dr. Shaalan Beg: Congratulations on your recently published article in the JCO CCI titled "Prediction of Effectiveness and Toxicities of Immune Checkpoint Inhibitors Using Real World Patient Data." Why did you decide to address this specific problem?
 
Dr. Travis Osterman: I am a practicing medical oncologist at Vanderbilt, I specialize in thoracic malignancies. Immunotherapy has been a significant part of my practice from the beginning. And I think for all of us, we have patients in our practices that are tremendous responders. I have stories of my patients, a few of which, at least, are able to get years of benefit even after stopping therapy, and potentially some even stage 4 patients that are amazingly seemingly cured after their treatments. But I also have patients that experience severe toxicities, some of those are life-threatening or life ending, but many of those carry morbidity. In my population, I see a lot of pneumonitis, and that really alters patients' quality of life. And the biggest conversation I have with patients is: “How do I know which of these outcomes I’m going to have, if I’m going to get benefits from these therapies or am I going to get one of these side effects or toxicities?” And we set out to try to answer that question with data.
 
Dr. Shaalan Beg: When electronic medical records started to make their way into the clinic, I remember all of us thinking about the wonderful applications where we could use the data to help guide the clinical care, assign the right treatment for the right patient at the right time, and learn from other patients' experiences to improve the care of the person who’s in front of us. And my personal opinion is that we haven’t realized our electronic medical records’ potential to that extent. And efforts like the one you published in JCO CCI is the culmination of one of the efforts, and I can only imagine how much time and effort it must have taken to develop that and we

Drs. John Sweetenham and Shaji Kumar discuss the emergence of CAR T-cell therapy for multiple myeloma, its benefits and challenges for patients, and its potential role earlier in the treatment of disease.
TRANSCRIPT

Dr. John Sweetenham: Hello, I'm Dr. John Sweetenham from the UT Southwestern Harold C. Simmons Comprehensive Cancer Center and host of the ASCO Daily News Podcast. 
Multiple myeloma is the second most common hematologic malignancy, and the American Cancer Society estimates that there will be more than 35,000 new cases of the disease diagnosed in the United States this year. The emergence of several novel therapies over the last decade has transformed the therapeutic landscape for multiple myeloma, and chimeric antigen receptor – or CAR T-cell therapy – is one of the newest treatments for this disease, which has created a great deal of buzz. 
Dr. Shaji Kumar is an internationally renowned investigator of novel therapeutics and next-generation treatment options for patients with multiple myeloma, and I'm delighted to welcome him to the podcast today to discuss innovations in CAR T-cell therapy in this space. Dr. Kumar is a professor of medicine and chair of the Myeloma Group, as well as chair of research in the Division of Hematology at the Mayo Clinic in Rochester, Minnesota. He is also the editor-in-chief of The Hematologist. 
You'll find our full disclosures available in the transcript of this episode, and disclosures of all guests on the podcast are available at asco.org/DNpod. 
Shaji, it's great to have you on the podcast today.
Dr. Shaji Kumar: Thanks, John.
Dr. John Sweetenham: Shaji, to begin with, maybe we could ask you for an overview of where CAR T-cell therapy sits in multiple myeloma right now. We know that CAR T-cell therapy has improved the survival for some patients with myeloma in recent years. But of course, relapse still remains a problem. Can you tell us a little about the therapies that are currently approved for multiple myeloma in the CAR T-cell space, and what are the potential benefits and challenges of these products?
Dr. Shaji Kumar: Absolutely. It has been a revolution, I think, in terms of therapies for multiple myeloma during the past decade. We have seen so many new treatments approved for myeloma, and consequently, the survival of patients with myeloma has significantly improved. Two decades ago, we used to tell patients a median survival of 3 years, and today we tell patients a median survival of 8 to 10 years, a number that is continuing to go up. And it is all because of the new treatments that have become available for patients, especially over the past decade, and CAR T-cell therapy has been a game changer.  
Now, the main treatments that we were relying on for the past 2 decades have been the immunomodulatory drugs, the proteasome inhibitors, and more recently, the anti-CD38 monoclonal antibodies. Unfortunately, what we see in the clinic is that patients go through these therapies and various combinations of these agents, and often over the 6 to 10 years after the diagnosis, they often become refractory to these drugs. And then we are left with very few choices, if any, for controlling the disease. And that's where the CAR T cells have really made an impact. 
Over the past several years, clinical trials have shown that CAR T-cell therapy is highly effective. In fact, when we look at the initial trials that have been done in this space, the majority of these CAR T cells have been targeted towards what we call BCMA, or a B-cell maturation antigen that is present on both normal and abnormal plasma cells. Now, the concept of CAR T cells has been around for a while, and we have already seen success in other hematological malignancies, but it has been a little late compared to the other diseases in terms of its arrival in the myeloma field. But over the past few years, we have seen some dramatic progress. We currently have two different CAR T cells that a

Drs. Hope Rugo and Sara Tolaney discuss the promise of antibody-drug conjugates (ADCs) in the treatment of breast cancer, highlighting key trials that shed light on matching the right ADC to the right patient in the right setting. They also explore how combinations and sequencing of ADCs can augment their efficacy, the mechanisms of resistance, and the future potential of biomarkers to predict patient response.
TRANSCRIPT
Dr. Hope Rugo: Hello, I'm Dr. Hope Rugo, your guest host of the ASCO Daily News Podcast today. I'm a professor of medicine and director of breast oncology and clinical trials education at the University of California, San Francisco's Comprehensive Cancer Center.
Antibody-drug conjugates, or ADCs, are rapidly changing the treatment landscape for patients with breast cancer. ADCs consist of antibodies that target tumor-specific antigens on the cell surface, chemical linkers, and cytotoxic payloads that can act powerfully to kill cancer cells. On today's episode, we'll be discussing advances in research to match the right ADC to the right patients and in the right setting. We'll also talk about the next steps, assessing how combinations and sequencing of ADCs can augment their efficacy, improve options for patients, and identify biomarkers in the future to predict how patients will respond so that we can match the right treatment to the right patient and their tumor. We need to gain a better understanding of the mechanisms of resistance that occur upfront as well as under the pressure of treatment. 
Joining me for this important discussion is Dr. Sara Tolaney. Dr. Tolaney is an associate professor of medicine at Harvard Medical School, associate director of the Susan Smith Center for Women's Cancer, and chief of the Division of Breast Oncology at the Dana-Farber Cancer Institute in Boston. 
You'll find our full disclosures in the transcript of this episode and disclosures of all guests on the podcast are available at asco.org/DNpod.
Dr. Tolaney, we're delighted to have you on the podcast today. Thanks for being here.
Dr. Sara Tolaney: Thank you so much for having me. I'm looking forward to the discussion.
Dr. Hope Rugo: Great! So, we'll move forward, and because we're friends and colleagues, I'm going to refer to you as Sara, and I'm Hope, since we’ll dispense with formalities in our discussion. 
A lot of the talks that we give about ADCs start out with “a revolution in breast cancer therapy.” And indeed, this is a really exciting time with ADCs as treatment for breast cancer, and we're rapidly moving these agents into earlier disease settings. Can you tell us a little bit about the possibilities and challenges of using ADCs for the treatment of breast cancer today?
Dr. Sara Tolaney: It's interesting that you say antibody-drug conjugates as revolutionizing outcomes of breast cancer, which I think is true. But on the flip side, I think it's also bringing up a lot of questions about how to use them, when to use them, and how to manage side effects. So there are a lot of good strengths for these antibody-drug conjugates, but a lot of unknowns that we're still trying to figure out. We had an older antibody-drug conjugate T-DM1 that we were all very familiar with that for years had been a treatment that we used very commonly in metastatic disease and now even use in early breast cancer, and I think has changed outcomes for patients. But over time, we've been able to develop newer antibody-drug conjugates as the technology has really evolved so that these agents now are able to deliver a lot of chemotherapy into a cancer cell. We're seeing very high drug-to-antibody ratios, and we're also seeing that these drugs can function via bystander effect, whereas T-DM1, for example, was not able to do that. But our newer ADCs, like sacituzumab govitecan or trastuzumab deruxtecan, are agents that do allow chemotherapy to get into that cancer cell, but also to get into neighboring cells. 
And I think

Drs. Shaalan Beg and Rachna Shroff discuss key abstracts on GI cancers that were featured at the 2024 ASCO Gastrointestinal Cancers Symposium, including SKYSCRAPER-08, EMERALD-1, and NEST-1 in esophageal squamous cell carcinoma, hepatocellular carcinoma, and colorectal cancer, respectively.
TRANSCRIPT
Dr. Shaalan Beg: Hello, and welcome to the ASCO Daily News Podcast. I'm Dr. Shaalan Beg, your guest host of the podcast today. I’m an adjunct associate professor at UT Southwestern's Simmons Comprehensive Cancer Center and vice president of oncology at Science 37. Today, we'll be discussing key abstracts and other exciting highlights from the 2024 ASCO Gastrointestinal Cancers Symposium. Joining me to discuss some key takeaways from the meeting is the chair of this year's Symposium, Dr. Rachna Shroff. Dr. Shroff is the division chief of Hematology Oncology and chief of GI Medical Oncology at the University of Arizona Cancer Center. She also serves as the associate dean for clinical and translational research at the University of Arizona College of Medicine – Tucson.
Our full disclosures are available in the transcript of this episode, and disclosures related to all episodes of the podcast are available at asco.org/DNpod. 
Dr. Shroff, welcome back to the ASCO Daily News Podcast, and congratulations on a great Symposium. The scientific advances and innovative, multidisciplinary approaches that were featured throughout the meeting were really inspiring and reflect the incredible strides we’re making in GI cancer research.
Dr. Rachna Shroff: Thank you so much for having me back. I am delighted to be here. 
Dr. Shaalan Beg: Dr. Shroff, the theme of this year's symposium was "Taking Personalized Care to the Next Level." I’d love to hear your reflections on the sessions that you found most exciting and really resonated with the attendees. 
Dr. Rachna Shroff: Yes, thank you. We were really excited about this theme because we really felt that “Taking Personalized Care to the Next Level” translated to thinking through personalized approaches to patient care, not just in the traditional ways that we think of with precision oncology and genomics driving our care, but also how we can think through multidisciplinary approaches and an individualized care plan. Thinking through how artificial intelligence and novel clinical trial designs can and should be implemented to meet the needs of our individual patients. And so we really highlighted that in what was a somewhat new reboot of a session called “Intersections,” which were every day and were really more cross-tumor; they were tumor agnostic but were thematic focused. As I mentioned, those themes were really based on feedback that we had from prior attendees, as well as from the program committee’s feeling on what are really the questions that we are dealing with and that are burning in the clinic today and that includes the emerging role of artificial intelligence and machine learning and how we integrate that into our clinical care, approaches to oligometastatic disease, and it’s not really just something that we think of in colorectal cancer but haven’t fully used that paradigm to really apply it to other GI malignancies. And then the art and science of clinical trial design where, again, traditional randomized phase 3 trials might not be the best and most innovative and most expedient way of bringing novel therapeutics to our patients. And so, I thought that all of those sessions were really highlighting different important topics that we deal with day to day.
Additionally, we had a really fantastic keynote lecture from Dr. Kimmie Ng of the Dana-Farber Cancer Institute. She is a world-renowned expert in the early-onset colorectal cancer space, and the timing of her keynote was perfect with the new cancer statistics that came out literally days before GI ASCO that demonstrated this just dramatic rise in early onset GI malignancies as a whole, not