Journal of Clinical Oncology (JCO) Podcast American Society of Clinical Oncology (ASCO)

TRANSCRIPT
The disclosures for the guest on this podcast can be found in the show notes.
 Davide Soldato: Welcome to this JCO Article Insights episode for the March issue of JCO. This is Davide Soldato, and today I will have the pleasure of interviewing Dr. Frédéric Amant, corresponding author of the manuscript titled ‘Cognitive and Behavioral Development of 9-Year-Old Children After Maternal Cancer During Pregnancy: A Prospective Multicenter Cohort Study’ (10.1200/JCO.22.02005). Dr. Amant is a professor at the Ku Leuven in Belgium and at the University of Amsterdam, and he is the head of the Department of Gynecological Oncology of the Netherlands Cancer Institute and the Amsterdam University Medical Centers.
Welcome, Dr. Amant.
 Dr. Frédéric Amant: Hello, good evening. Thank you for the introduction.
 Davide Soldato: So, Dr. Amant, you published this manuscript that reports the updated results of an ongoing prospective multicenter study. And this study is actually investigating cognitive and health outcomes in nine-year-old children that were born from women who were diagnosed and treated for cancer during pregnancy. So I wanted to ask if you could give us just a quick overview of the study design. What are the main outcomes that are investigated in the study, and also if you could give us some information about the results that you recently published in the JCO?
 Dr. Frédéric Amant: Well, the study is a follow-up study of children that are now nine-year-olds. A large part of these children, we have been following up since birth. So the first paper on this cohort basically was in 2015. And at that stage, children were 18 to 30 months old. Well, what we have to say is that all these children, or the majority of these children, in fact, the mothers, were exposed to chemotherapy during pregnancy. So the results actually in children at 18 or 30 months were, in fact, reassuring. And at that time, that was actually a big novelty because it was the first study where children were prospectively followed up and when they were compared to a control group. This study was actually changed a bit; the idea that chemotherapy during pregnancy was not possible. From there, we started to further follow up to some extent the children, but also it increased the awareness that we can treat cancer during pregnancy, including chemotherapy during pregnancy.
 This was followed up by a study two years ago in six-year-old children that was, in fact, also reassuring. Today, we discuss then the cognitive and the behavioral development of nine-year-old children when the mother was exposed to chemotherapy but also, in fact, cancer; all the diagnostic investigations, many women also received surgery, and actually, the children were controlled by researchers, by psychologists, by medical doctors to look into their general health. There were questionnaires to the parents, and then we assessed the IQ, we assessed memory tasks, and attention tasks.
 Overall, the results are, in fact, reassuring for the several subtypes of treatments, including several subtypes of cytotoxic drugs, and there were no differences when we looked into the intelligence quotient, so the IQ between exposed and non-exposed children. We did see some interesting analysis, however. To some extent, we did see that, for example, the IQ score increased by 1.6 points for each week’s increase in gestational age. There was no difference in the full-scale IQ between the treatment types.
Actually, in children prenatally exposed to chemotherapy, there was no association between full-scale IQ and the chemotherapy drugs, exposure levels, or the timing of the chemotherapy during pregnancy. So overall, the results are reassuring and indicate that during a critical maturation period of the child, when complex functions start to develop already and rely on the integrity of early brain development, this is actually reassuring. Especially, this critical maturation period means

Dr. Shannon Westin and her guests, Jessica Star and Dr. Ahmedin Jemal, discuss how the COVID-19 pandemic affected cancer screening in the US in 2021.
TRANSCRIPT
The guest on this podcast episode has no disclosures to declare. 
Dr. Shannon Westin: Hello, everyone, and welcome to another episode of JCO After Hours. I am your host, Shannon Westin, the social media editor for the JCO and Gynecological Oncologist at MD Anderson. And it's my pleasure to welcome you to our next episode, which is “Cancer Screening in the United States During the Second Year of the COVID-19 Pandemic.” And please note the authors have no conflict of interest.  
I'm joined by two of the authors on this important work. First is Jessica Star, who has an MA and an MPH and is Associate Scientist II for Cancer Risk Factors and Screening Surveillance Research at the American Cancer Society. Welcome. 
Jessica Star: Thank you for having me. 
Dr. Shannon Westin: Of course. And we're also joined by Dr. Ahmedin Jemal, the Senior Vice President for Surveillance and Health Equity Science at the American Cancer Society. Welcome. 
We're so excited that you both are here, and I'm hoping that we'll have a really lively discussion about your important work. This paper was published online on February 23, 2023, in the Journal of Clinical Oncology. So let's level set. We'll start—Jessica, can you talk a little bit about how the COVID-19 pandemic initially impacted cancer screening in the United States? 
Jessica Star: So the COVID-19 pandemic disrupted the delivery and receipt of routine preventative services, and that included cancer screening. What we've seen from a lot of 2020 data that has been published is that cancer screening declined during that first year of the COVID-19 pandemic. One of those papers includes a paper by the American Cancer Society led by Stacey Fedewa. And many other studies also reported similar declines, including for breast, cervical, prostate, and colorectal cancer screening. However, some of these papers, by the end of 2020, it appeared that screening rates were starting to rebound back to pre-pandemic rates. And so that was sort of the interest in looking at that 2021 data now.
Dr. Shannon Westin: And what did you hypothesize? Did you think that these data were correct? Like, did you think that we were going to start seeing an increase in screening in the second year of the COVID-19 pandemic, or what were your suppositions?
Jessica Star: Yes, I think we kind of hypothesized or hoped, based off of what we were seeing from the 2020 data, that we would start seeing more substantial increases as we were getting into 2021. Based off of those declines during the first part of the pandemic, we were really wanting to see individuals coming back into screening now that stay-at-home orders had sort of been reduced and now that individuals were going back to screening more frequently.
Dr. Ahmedin Jemal: I might add that the motivation for this screening, in addition to what Jessica said, is that the previous studies were based on representative US populations, either based on claims data or state-specific population-based studies. They were not based on nationwide population-based study. That's why we used the NHIS, National Health Interview Survey, which is a US population-based study, to look at whether screening in 2022 has returned to the pre-pandemic level. 
Dr. Shannon Westin: Yeah, why don't we get into a little bit more detail here? I would love—Jessica, can you talk a little bit more about the National Health Interview Survey? I get the idea of why you all used it, but can you tell our listeners just a little bit more about that database?
Jessica Star: To go off of what Ahmedin mentioned, The National Health Interview Survey is a nationally representative cross-sectional household survey of the United States population that is generalizable. And that survey is housed by the National Center for Health Statistics in

Dr. Shannon Westin and her guests, Dr. Michael Atkins, Dr. Adil Daud, and Dr. Gary Schwartz, discuss a definitive work: The DREAMseq Trial.
TRANSCRIPT
The guests on this podcast episode have no disclosures to declare.
 
 
Dr. Shannon Westin: Hello, everyone, and welcome to another episode of JCO After Hours, the podcast that gets in-depth on articles that have been published in the Journal of Clinical Oncology. And it is my great pleasure to be your host. I'm Shannon Westin, GYN oncology, and I serve as the social media editor for the Journal of Clinical Oncology.
 
Today, we're going to be discussing a very exciting article describing “The DREAMseq Trial—ECOG-ACRIN EA6134, Combination Dabrafenib and Trametinib Versus Combination Nivolumab and Ipilimumab for Patients With Advanced BRAF-Mutant Melanoma.” This article was published in the JCO on January 10th, 2023.
 
And I am joined today by the lead author, Dr. Michael Atkins, who is Deputy Director, Georgetown Lombardi University Hospital, and Scholl Professor and Vice Chair of Oncology at Georgetown University Medical Center. Welcome.
 
Dr. Michael Atkins: Thank you. Nice to be here.
 
Dr. Shannon Westin: In addition, we are also accompanied by two experts in the field, Dr. Adil Daud, Professor in the Department of Medicine at the University of California San Francisco, and Director of Melanoma Clinical Research at UCSF Helen Diller Family Comprehensive Cancer Center. Welcome, Dr. Daud.
 
Dr. Adil Daud: Hi, great to be here.
 
Dr. Shannon Westin: And with Dr. Daud is Dr. Gary Schwartz, the Division Chief of Hematology Oncology and Deputy Director of the Herbert Irving Comprehensive Cancer Center in Columbia, New York. Thank you for being here.
 
Dr. Gary Schwartz: Delighted to be here.
 
Dr. Shannon Westin: So I'm surrounded by experts, and I'm very excited as a GYN oncologist to hear all of what you all have learned in melanoma because we're always excited to take that back into our field. So I think first, though, for those of us that aren't melanoma experts, Dr. Atkins, can you just level set for us and tell us what was the standard of care for melanoma when you began this study?
 
Dr. Michael Atkins: Sure. Well, first of all, this was a study for patients with BRAF V600 driver mutations in their melanoma, which represents about 50% of the patients with metastatic melanoma. And at the time the study was launched in 2015, two BRAF/MEK inhibitor combinations were FDA approved and shown to produce significant progression-free survival and overall survival benefits relative to BRAF inhibitor monotherapy. In addition, combination checkpoint inhibitor therapy with nivolumab and ipilimumab was shown to be superior to ipilimumab and, in particular in patients with BRAF-mutant melanoma, also to nivolumab monotherapy based on the results of the CheckMate 067 study, leading to its FDA approval. So we had these two regimens there that were approved. Of note, despite the many debates and attempts to garner real-world evidence at the time—the study actually reported out in 2021—marketing data showed that half of all patients in the US with metastatic BRAF-mutant melanoma were receiving BRAF/MEK inhibitors, and only one-quarter received nivo-ipi as initial therapy. So there remained a confusion throughout the course of the study as to which regimen was best in the US and around the world.
 
Dr. Shannon Westin: Tell me, what led to the current study? Was it really trying to drive at that very question?
 
Dr. Michael Atkins: These were the best treatment available at the time. And they really had changed melanoma patient outcomes in ways that we could have only dreamed about just five to 10 years prior, when median survival for patients with metastatic melanoma was six to nine months. Hence, the DREAMseq trial, this doublet, randomized evaluation of advanced melanoma sequencing, was really an apt acronym for the trial. But we had these

In this JCO Article Insights episode, Emily Zabor summarizes two articles from the February 20th, 2023 Journal of Clinical Oncology issue: "Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non–Small-Cell Lung Cancer: The Phase III POSEIDON Study" by Johnson, et al  and "The POSEIDON Trial: Will Secondary End Points Change Our Clinical Practice?" by Remon, et al.
The Original Report by Johnson, et al describes results of the Phase III POSEIDON clinical trial. The accompanying editorial by Remon, et al discusses the findings of a significant progression-free survival and overall survival benefit for the combination of tremelimumab plus durvalumab plus chemotherapy as compared to chemotherapy alone, which were secondary endpoints in the trial.
TRANSCRIPT
Emily Zabor: Welcome to JCO Article Insights for the February 20, 2023, issue of JCO. I’m your host, Emily Zabor, JCO Biostatistics Editorial Fellow. 
Today, I will be providing summaries for two articles. The first article, titled ‘Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non–Small-Cell Lung Cancer: The Phase III POSEIDON Study,’ by Dr. Melissa Johnson and colleagues, describes the results of the Phase III POSEIDON clinical trial. POSEIDON was a randomized Phase III clinical trial in patients with metastatic non-small cell lung cancer. The trial had a three-arm design to evaluate the efficacy of tremelimumab plus durvalumab plus chemotherapy; durvalumab plus chemotherapy; and chemotherapy alone in a first-line treatment setting. The two immunotherapies were selected for study because of their complementary mechanisms of action. Tremelimumab is an anti-CTLA-4 antibody which can diversify T-cell responses and lead to increased tumor infiltration. Durvalumab is an anti-PDL1 antibody which can enhance T-cell function. Chemotherapy is still an important treatment option for early disease control and potential for immune priming.
Patients in the POSEIDON trial were randomized to the three arms with equal allocation. The co-primary endpoints for the trial were progression-free survival and overall survival for the comparison of durvalumab plus chemotherapy vs. chemotherapy alone. Then, a hierarchical multiple-testing procedure with a gatekeeping strategy was used across the primary endpoints and key secondary endpoints. Gatekeeping procedures are a way of controlling the type I error rate across multiple groups of null hypotheses that have a hierarchical structure, meaning that some of the hypotheses are considered more important than others. In this case, the plan was to first test for differences in progression-free survival and overall survival between the durvalumab plus chemotherapy and chemotherapy alone arms. Then, if either of those tests had a significant p-value so that the null hypothesis of no difference between groups was rejected, tests for differences in progression-free survival and overall survival between the tremelimumab plus durvalumab plus chemotherapy and chemotherapy alone arms would be conducted. Additional levels of testing could be conducted for other secondary endpoints following significance at the previous level. These types of gatekeeping procedures are a rigorous way of controlling the type I error of the entire study at 5% while still allowing multiple tests to possibly be conducted.
The efficacy analyses were conducted in the intention-to-treat population, which included 338 patients on the tremelimumab plus durvalumab plus chemotherapy arm, 338 patients on the durvalumab plus chemotherapy arm, and 337 patients on chemotherapy alone. The median follow-up among those without an event was 10.3 months for progression-free survival and 34.9 months for overall survival. The findings for the co-primary endpoints were that progression-free survival was significantly improved with durvalumab plus chemotherapy ver

Dr. Shannon Westin, Dr. Ezra Bernstein, and Dr. Nadir Arber discuss increasing cancer prevention and early detection with a one-stop-shop comprehensive cancer screening center.
TRANSCRIPT
The guest on this podcast episode has no disclosures to declare.
Dr. Shannon Westin: Hello, everyone, and welcome to another episode of JCO After Hours, our podcast where we get in-depth on manuscripts that have been published in the Journal of Clinical Oncology. I am your host, Shannon Westin, GYN oncologist and social media editor of the JCO. And I am thrilled to be discussing this very interesting paper entitled “Data From a One-Stop-Shop Comprehensive Cancer Screening Center,” focused on asymptomatic screening.
And this very important work was published by these two authors who are joining me today. We have Dr. Nadir Arber, professor of Medicine and Gastroenterology, head of the Integrated Cancer Prevention Center, head of the Cancer Prevention section of the European Society of Medical Oncology at Tel Aviv Sourasky Medical Center in Tel Aviv, Israel. And we're also joined by Dr. Ezra Bernstein, Fulbright fellow and researcher at the Integrated Cancer Prevention Center that we're going to be discussing today at Tel Aviv Sourasky Medical Center in Tel Aviv, Israel. And he's also, impressively, a resident in internal medicine at the New York University, so he's a gentleman of many talents and quite busy.
Welcome.
Dr. Ezra Bernstein: It's great to be here. I had a slow clinic day.
Dr. Shannon Westin: Oh, I was going to say I'm impressed you, as a resident, could find the time. So we're really excited to have you, and you certainly have a bright future ahead of you as an oncology practitioner.
So let's get started. I think certainly most of our listeners are quite familiar with the benefits of cancer screening. But I think it would be great if you all could level set and review the benefits at the patient level as well as at the healthcare system level.
Dr. Ezra Bernstein: Sure. So I think, kind of breaking it down, on the patient level, the scientific community has made incredible progress over the last several decades in not only the understanding of the biology of cancer, but also that's translated into the treatment of cancers, from genomic sequencing to targeted therapy, which you now have specific small molecule inhibitors for specific mutations in each cancer. But despite all these incredible improvements and advances and the ability to treat many cancers, the greatest prognostic factor is still often the stage of diagnosis because the chances of survival and the chances of complete cure increase dramatically if the disease is detected in its earlier stages. So earlier detection and diagnosis can greatly reduce mortality, it can increase treatment effectiveness, and ultimately improve the quality of life for the cancer patients.
On a healthcare system level, often when you're doing screening, you're discussing cost-effectiveness. And so the thing about the healthcare system, which we didn't really address in our paper–we initially were going to, but we think we're going to do a follow-up paper on this–the cost of cancer care is very high. In Europe, the total cost of cancer care in 2018 was $199 billion. And then I think the last data I saw was the US, in 2015, the total cost of cancer care was $183 billion. So, on a healthcare system level—and those are just the costs of cancer care; there's tons of other costs that go into when patients have cancer: lost wages… So I think that it's crucial not only for the patient but also for the healthcare system to help catch these cancers earlier.
Dr. Shannon Westin: Yeah, I completely agree. I think we have such great guidelines on how we should be screening our patients. I think there's a number of different areas where providers can look to understand what they should be doing with the patient in front of them. What do you think are some of the barriers of implementat

Dr. Shannon Westin and her guests, Dr. Paul Frankel, Dr. Judith Karp, and Dr. Robert Maki discuss how to better inform patients of the risks involved in phase 1 clinical trials.
TRANSCRIPT
Dr. Shannon Westin: Hello, everyone, and welcome to another episode of the Journal of Clinical Oncology After Hours podcast, where we do a deep dive on manuscripts that are published in the Journal of Clinical Oncology. We're so excited to have you all here today. I am your host, Shannon Westin, GYN Oncologist at MD Anderson Cancer Center, and it's my great pleasure to serve as the social media editor of the JCO and the host of this podcast. Today we are going to be discussing a very important manuscript titled “Ethics and Clinical Research: Improving Transparency and Informed Consent in Phase 1 Oncology Trials”. And I'm joined today by several of the authors, as well as one of our editors that helped to review this paper. But before I start, I'll note that none of our authors have any conflicts of interest to disclose. And with that, I'd like to introduce our guests.
First is Dr. Paul Frankel. He's a research professor at the Division of Biostatistics, Department of Computational and Quantitative Medicine, at the City of Hope National Medical Center. Welcome.
Dr. Paul Frankel: Hello and thank you. It's a great honor to be here today.
Dr. Shannon Westin: Also with Dr. Frankel is Dr. Judith Karp, who is Professor Emerita of Oncology and Medicine at the Johns Hopkins University School of Medicine in Baltimore, Maryland. Welcome.
Dr. Judith Karp: Thank you. And I echo exactly what Paul said. Thank you for having me.
Dr. Shannon Westin: And then finally, our esteemed Associate Editor of the JCO, Dr. Robert Maki. He's a professor of hematology and medical oncology, a physician leader in developmental therapeutics, clinical leader of the Sarcoma program at the University of Pennsylvania.
Dr. Robert Maki: Hi, Shannon. Thanks for having me on the program.
Dr. Shannon Westin: Well, it's awesome to have this star-studded group of guests. We are going to try to cover as much details about this important paper as we can in a short period of time. But I encourage you also to check out the JCO to read the paper in full. So first, let's level set. As we start this discussion around phase 1 trials and ethics, maybe, Dr. Mackie, can you start by giving the basics of just phase 1 trials just to make sure everyone's on the same page?
Dr. Robert Maki: Sure, absolutely. Since we have people who are listening from different walks of life, that's for sure. Clinical trials in cancer run anywhere from phase 1, 2 to 3. There are also such things as phase 0 and phase 4 trials. But the primary ones we'll discuss today are phase 1 trials. These are the initial tests, be there a brand-new drug never tested before in people, or it might be testing a new combination of treatments, or it might be looking at an already approved drug or an experimental drug in a new population of patients. Let's say you wanted to take a look at a drug in an elderly population. There aren't any data about that in people who are, let's say, 80 or older, and that would constitute a phase 1 trial. The idea of the trial is to start with low doses of a medication and increase the doses in a systematic way, tracking the side-effects that occur with treatment, and then come to an answer as to how you should move forward with the medication in future trials to determine whether the drug is actually active or not and in which setting. The important point, I guess, in that sense is that a phase 1 trial isn't necessarily looking at whether a drug is useful or not, really just looking at the toxicity of the agent or new combination or new setting overall.
Dr. Judith Karp: If I could add one thing to that, and I think this is something that has evolved—well, it's evolved over the last 30 years, but in terms of practicality and application, it's really over the last 10 years, roughly spe