In this week’s episode of The Cancer Letter Podcast, Paul Goldberg, editor and publisher of The Cancer Letter, and Sara Willa Ernst, reporter, break down HHS’ latest vision for the future: Operation Trailblazer.
This episode is available on Spotify, Apple Podcasts, and Youtube.
The report is titled: “HHS Roadmap to Maintaining U.S. Leadership in Early Clinical Research and Development.”
“The U.S. is apparently losing its leadership in INDs and early phase research,” Paul said. “Some of it is true and also it does not help that the whole enterprise of cancer research right now is in, if not disarray, then at least a kind of mental and spiritual discombobulation.”
Most notable were proposed changes to FDA, including an expedited Investigational New Drug program, which would use expertise outside FDA to help prepare INDs before submission, and a lower threshold—just one high-quality late-stage—for confirmatory evidence, which is already common practice in oncology.
Paul checked in with sources about the report after it was released. What he heard with his ear to the ground: It’s unclear whether the plans in the report will amount to policy.
“We don’t know whether it’s going to happen and there is a problem right now in that FDA really took a hit in terms of staffing,” Paul said. “At the moment, there is no permanent FDA commissioner. Having leadership that’s deeply destabilizing was really a problem.”
“FDA really right now needs to get its house in order or as the industry says, ‘right the ship,’” he continued. “A rudderless FDA for a while there was a step in the wrong direction. So, they’re going to have to clean this up and maybe they will. Let’s hope they do.
“That’s what I’m hearing from folks as I call them. But it was important to get [the news] out on paper even though the story certainly has a large number of caveats.”
Stories mentioned in this podcast include:
- The Directors: Directors of two Midwestern cancer centers tell us about the challenging healthcare economics in rural areas
- To keep the early clinical trial enterprise in the U.S., HHS pledges to simplify regulatory requirements
- Joe Fraumeni, founder of molecular epidemiology, dies at 93
- Karen Huntsman’s vision gave shape to the Huntsman Cancer Institute
- Robert Mayer tells us about pancreatic cancer’s hopeless past as new data shows promise
This episode was transcribed using transcription services. It has been reviewed by our editorial staff, but the transcript may be imperfect.
The following is a transcript of this week’s In the Headlines, a weekly series on The Cancer Letter Podcast:
Jacquelyn Cobb: This week on the Cancer Letter Podcast.
Paul Goldberg: Well, one confirmatory trial, a lot of that has been happening in oncology for a very long time, so you’re lucky to have one randomized trial. So, it’s conversation. Looking at, asking people who are involved in drug development, which I did, if there was dancing in the streets, I didn’t see it. Okay. It was dancing on another street.
Sara Willa Ernst: It might be hard to tell at this point with World Cup and…
Paul Goldberg: No, no, no. Different streets.
Sara Willa Ernst: Different streets.
Paul Goldberg: If there were dancing in the streets, we would see dancing in the streets. No.
Sara Willa Ernst: Yeah.
Paul Goldberg: Yeah. There’s a lot of kind of like, “Yeah, I don’t know,” in the streets, that kind of attitude which is… I showed it to several group chairs and all of them said, “I don’t know” basically.
Sara Willa Ernst: Well, is it because there’s just like, is this really going to happen or not? It’s more skepticism or…
Paul Goldberg: Yeah, yeah. It’s interesting to see it. It’s nice to put it on record. I have no idea what it means and I’m not unique in this one because I don’t think anybody else knows what it…
Paul Goldberg: You’re listening to the Cancer Letter Podcast. The Cancer Letter is a weekly independent magazine covering oncology since 1973. I’m your host, Paul Goldberg, editor and publisher of the Cancer Letter.
Jacquelyn Cobb: And I’m your host, Jacquelyn Cobb, associate editor of The Cancer Letter. We’ll be bringing you the latest stories, groundbreaking research and critical conversations shaping oncology.
Paul Goldberg: So, let’s get going.
Sara Willa Ernst: Hi, Paul.
Paul Goldberg: Hi, Sara. How are you?
Sara Willa Ernst: Good. I think this is week two of the Sara Willa Ernst and Paul Goldberg podcast, right?
Paul Goldberg: Indeed.
Sara Willa Ernst: We chatted last week. We’re going to chat again this week and we’re going to talk about a stacked issue. Should we jump right in?
Paul Goldberg: Yeah, yeah, yeah, of course. What’s there to wait for?
Sara Willa Ernst: So, last week, our cover story was about a conversation Paul had with two cancer center directors. We also had a podcast, The Directors, in which he spoke to Mark Burkard with the University of Iowa Holden Comprehensive Cancer Center and also Jeffrey Miller with the University of Minnesota Masonic Cancer Center. And the three of them talked about the challenges of rural healthcare, particularly with the finances of it, some of the looming Medicaid cuts coming from The One Big Beautiful Bill. And these institutions right now are just feeling really crunched and that crunch is coming from a bunch of different directions.
Then we had story two, which is going to be the center of our conversation today. This is a Paul Goldberg written story and that was about Operation Trailblazer, which is this report that’s come out that basically lays a vision for FDA, NIH, and ARPA-H. And so, we’ll dig into that, but I’ll go through the rest of the issue.
Then we had two obituaries. The first one was just a really beautifully written obit, chock-full of history, about Joe Fraumeni, who died at the age of 93.
And then we had one other obit, which was about Karen Haight Huntsman. She passed away at 88 and the story was really about what she meant for the Huntsman Cancer Center at the University of Utah.
And then the very last story is my story, which we’re also going to talk about. This is a Cancer History Project / In The Archive’s story. So, there’s also another podcast if y’all want to listen to the extent of it. And this is with Robert Mayer with Dana-Farber Cancer Center and Harvard. And we talked about the history of pancreatic cancer and how we kind of arrived at this particular moment. And we talked about some of the data that was presented at ASCO that erupted in this 43-second standing ovation and what were all of the kind of trials and errors and the swings and the misses along the way to get to daraxonrasib, which I really do not know how to pronounce that well.
But yeah, there were a couple of cancer policies. We had a couple of interesting briefs and clinical roundups, but that was the extent of the issue.
Why don’t we jump into the story that Paul wrote? This was specifically about the report that came out or the draft guidance. And I mean, why don’t you just tell us really what was at the heart of it? What do you think was most noteworthy?
Paul Goldberg: Well, what was most noteworthy is that the U.S. is apparently losing its leadership or lead in INDs and early phase research and what needs to be done in order to fix that. And HHS published kind of a whole series of things and rolled them all out saying, “This is how we’re going to do it throughout the department.” And it’s all very interesting to put it all in one place. Most of it seems to be at FDA. Some of it really goes way back, but some doesn’t. One of the highlights is a plan for an expedited IND program, which basically uses expertise outside FDA as well to prepare or to help shape the actual INDs that go to FDA.
Well, it’s here the proof is going to be depending on A, we don’t know whether it’s going to happen. B, there is a problem with FDA right now in that, FDA really took a hit in terms of staffing. And at the moment, there is no permanent FDA commissioner. So, that’s what I’m hearing from folks as I call them, but it was important to get it all out on paper even though the story certainly has a large number of caveats. Yeah, maybe. Maybe it’ll be good. Some of it was more better shaped, better clear. Some of it was more clear. Some of the initiatives were more clear than others, but we’ll see.
Sara Willa Ernst: So, talking to your sources, there’s a little bit of this question mark of, okay, you’re talking about all of these big changes, but how would you actually practically pull it off? Is that kind of what you’re hearing on the ground?
Paul Goldberg: Yeah. FDA really right now needs to get its house in order or as the industry says, needs to write ship. And this idea of changing clinical trials. Well, yeah, that’s been discussed since the beginning of the administration that they’re going to do that. Would they do it in a way that’s meaningful? Well, I would say that DOGE was a step in the wrong direction. A rudderless FDA for a while there was a step in the wrong direction. So, they’re going to have to clean this up and maybe they will. Let’s hope they do. And it’s also having leadership that’s really deeply destabilizing was really a problem.
Sara Willa Ernst: What are the potential implications of rolling IND and what are the potential implications of only needing one confirmatory trial?
Paul Goldberg: Well, one confirmatory trial, a lot of that has been happening in oncology for a very long time. So, you’re lucky to have one randomized trial, so it’s conversation. Looking at asking people who are involved in drug development, which I did. If there was dancing in the streets, I didn’t see it. Okay. It was dancing on another street.
Sara Willa Ernst: It might be hard to tell at this point with World Cup and-
Paul Goldberg: No, no, no. Different streets.
Sara Willa Ernst: Different streets.
Paul Goldberg: If there were dancing in the streets, we would see dancing in the streets. No. Yeah. There’s a lot of kind of like, “Yeah, I don’t know,” in the streets, that kind of attitude, which is I showed it to several group chairs and all of them said, “I don’t know,” basically.
Sara Willa Ernst: Well, is it because there’s just like, is this really going to happen or not? It’s more skepticism of-
Paul Goldberg: Yeah, yeah. It’s interesting to see it. It’s nice to put it on record. I have no idea what it means and I’m not unique in this one because I don’t think anybody else knows what it means. It’s not necessarily a thing that’s going to make things better. There has been a lot of discussion at NCI, which I’m more interested in about improving clinical trials in oncology, but that’s separate and different from this.
Sara Willa Ernst: Well, I did want to ask you about NCI. Notably, the report talks about FDA, NIH, ARPA-H, but NCI is not in the report.
Paul Goldberg: It was not…
Sara Willa Ernst: I’m just wondering if…
Paul Goldberg: Yeah, it was not part of the rollout. I think we’re making a lot out of essentially a political development, which is interesting and worth covering and we covered it and now we move on and look and see if there’s any implementation, if there’s any impact, if that’s even traceable to what just happened or I’m not even sure what just happened actually and I’m closer to it than most people.
Sara Willa Ernst: Yeah. Well, the premise of the report, I mean, I’m going to pull out one quote from the top of your story, which is RFK Jr. saying that we need to restore America’s leadership in clinical research, remove unnecessary barriers, and bring more clinical research and investment back to United States, kind of saying that we’re losing, we’re losing on the global stage.
Paul Goldberg: Well, and some of it is true and also it does not help that the whole enterprise of cancer research right now is in if not disarray then at least a kind of mental and spiritual discombobulation. So, that’s another question and I don’t think there will be an HHS rollout there on that one, but it does keep HHS focused on something that’s positive. So, that’s a good thing. That’s another comment I got from someone who didn’t want to be quoted.
Sara Willa Ernst: Well, we could also talk about my story, which has to do with Bob Mayer. This was a Cancer History Project story. So, we’re talking about multiple decades of cancer research just kind of packed into one podcast and one story. But yeah, Jacquelyn Cobb spoke with Robert Mayer. He is the faculty vice president for Academic Affairs at Dana-Farber Cancer Center and the faculty associate dean for Admissions at Harvard Medical School. And I mean, he started practicing medicine in 1969. So, we’re talking about really a long span of time. I mean, from what I can tell, Paul, you can tell me if I’m wrong, he’s like a total legend in oncology.
Paul Goldberg: He’s a mensch. He’s a mensch.
Sara Willa Ernst: Yeah. I mean, he talked about in his early career, he was part of something called the NCI-supported Gastrointestinal Tumor Study Group. This was pretty soon out of residency for him and they were focused on GI cancers, including pancreatic cancer. And he was telling Jacquelyn about how, I mean, essentially compared to the standards of today, they were rummaging around in the dark. I mean, they were trying to develop and test hypotheses without a lot of the modern tools of today like CT scans, which I’m not an oncologist, but I can imagine that being a huge, huge hindrance into just formulating educated questions and to know what you’re talking about. But yeah, pancreatic cancer has come a very long way and yeah, they talked about many of the steps.
Paul Goldberg: Yeah. The term that Bob doesn’t use, but I love is paleo-oncology. And how do you go from-
Sara Willa Ernst: Oh, what’s that?
Paul Goldberg: Paleo as in…
Sara Willa Ernst: Like the paleolithic era?
Paul Goldberg: Right. So, it’s kind of the…
Sara Willa Ernst: Or like the paleo diet. Nevermind.
Paul Goldberg: No, no, not diet.
Sara Willa Ernst: Not that.
Paul Goldberg: But they are sort of interconnected in a strange way, but that term of how it was done and he’s seen all of that and he’s seen the evolution, and he trained at many, many, many docs who have made change happen and having him talk about recent advances in pancreatic cancer was really illuminating and in a way, it’s a nice way to look at, gee, what has the United States done with the money that has been spent on cancer research? Well, there you go. Here it is. So, it’s very real. Look at these curves. Yeah. But of course, it’s been a long time and a lot of money, but the money was well spent. We could have done better with more money.
Sara Willa Ernst: Yeah. And that’s definitely something that he talks about, which is making the case of… We should continue to study this and there should be federal funding and other sources of funding to really support this. I think one thing that was really interesting about the podcast was just hearing somebody who has seen the progression throughout the decades talk about this particular moment and talk about how really the perception or his perception or his colleagues around him saw pancreatic cancer as a hopeless situation. And that’s the way they saw it in the ’70s, the ’80s, the ’90s, even till pretty recently. And yeah, it’s like not until this moment where there’s starting to be a pivot in a different direction where people are starting to feel some hope around this disease.
Paul Goldberg: Definitely. I guess I’m not as much into the word hope on this one because its results are still pretty devastating. However, the hope is for future advances in this disease…
Sara Willa Ernst: Totally.
Paul Goldberg: It’s a privilege to be covering it and it’s one of the reasons it’s a great time to be a journalist.
Sara Willa Ernst: Yeah. And Robert Mayer, at this moment he’s like, there are so many questions that this one discovery spurs. I’m just going to list some of the questions that he has at the top of his mind, but it’s, do you give a RAS inhibitor before an operation? Could you shrink the tumor? What happens if you fail or the disease returns and is this the only RAS inhibitor of its class? He compared it to CML and he said, “Yeah, there was a first drug that seemed to work, but it wasn’t really the best outcome.” And from there, future discoveries were made on top of it.
Paul Goldberg: Well, in GI oncology, really there was a doubling of overall survival that occurred basically one little bit at a time, one clinical trial at a time. Until about now where things are getting even better. So, it’s incremental.
Sara Willa Ernst: Yeah. And that’s how it happens.
Paul Goldberg: Yeah. And again, it’s a terrific time to be a journalist. What’s cool about that Q&A is that you just have to… It kind of speaks for itself. It’s worth listening to on the drive. I enjoyed it immensely.
Sara Willa Ernst: Yeah. This is just our shameless plug to get people to listen to the Cancer History Project Podcast.
Paul Goldberg: Right, right. And speaking of history, one of the things that I really loved about this issue is just the overall theme of standing on the shoulders of giants. And one bit is Joe Fraumeni obit, which is probably… it was written by Stephen Chanock. It’s probably one of the most… One of the pieces I most enjoyed really in months and years possibly.
Sara Willa Ernst: Yeah. It was really beautifully written.
Paul Goldberg: Yeah. I read it, then I read it again, and then I read it again. It was kind of like, “Holy mackerel.” And what a giant, what a giant. Here’s a guy who basically superimposes molecular biology onto classical genetics and just kind of combines them to create a molecular epidemiology that’s kind of wow and peerless. Well, peerless until he trained his peers. So, in that sense, he’s way ahead of his time and we all were as giants walk the earth, we could see them. We could say hello. He could call Joe and say, “What’s going on about whatever?” And have a nice off-the-record conversation.
Sara Willa Ernst: Well, the giant lives on in bits and pieces of all of the people that he’s trained throughout the years and professionals that he’s touched and influenced.
Paul Goldberg: The whole field, the whole field and he created it. Yeah. It was an interesting issue with a theme to it, which it takes efforts of a lot of people over a very long time to get us where we are.
Paul Goldberg: And I guess we should also mention the other obit, right? Mrs. Huntsman.
Sara Willa Ernst: Karen Huntsman.
Paul Goldberg: Yeah, yeah. Because it’s just amazing to see someone who put money into the treatment of cancer in her world and so much of it and who played a role in this philanthropy because it was hers as much as it was her husband. And these are people who really believed in fighting the fight. My only interactions with her late husband, John Huntsman, was when an effort was made to, I would say, destroy what was done with the Huntsman Cancer Center.
Sara Willa Ernst: Oh.
Paul Goldberg: Oh yeah, this was a great story and that was some years ago, but he basically stopped it. So, it’s an interesting story, it’s worth looking at. But of course that’s not the Karen Huntsman’s story. She cared passionately about what was happening at the Huntsman Cancer Institute and she cared passionately about what things looked like about how the place treated the entire patient. And the art! My God, the art collection there is extraordinary and that was a collection that she donated and put together and the architecture and the light and all of that is really fantastic. So, a lot of giants.
Paul Goldberg: Yeah, I should probably tell you what’s coming up. The Joe Fraumeni story was so fantastic that we are going to make a conversation about the part of the Cancer History Project that’s coming up, I would say, well in the next few weeks.
Sara Willa Ernst: Yeah, in July.
Paul Goldberg: In July. So, that should be really interesting to listen to. So, thank you very much.
Sara Willa Ernst: Thank you so much, Paul. Yeah. We’ll have a Sara Willa Ernst, Paul Goldberg podcast sometime soon.
Paul Goldberg: All right, we’ll do it. Talk to you soon.
Paul Goldberg: Bye.
Paul Goldberg: Bye-bye.
Jacquelyn Cobb: Thank you for joining us on the Cancer Letter Podcast, where we explore the stories shaping the future of oncology. For more in-depth reporting and analysis, visit us at cancerletter.com. With over 200 site license subscriptions, you may already have access through your workplace. If you found this episode valuable, don’t forget to subscribe, rate, and share. Together, we’ll keep the conversation going.
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