26 min

A Revolution in Immunotherapy for Cervical and Endometrial Cancers ASCO Daily News

    • Medicine

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

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

26 min