The Ongoing Legacy of Felix Feng Team Science
Dr. Felix Feng Legacy Lecture: The Ongoing Legacy of Felix Feng Team Science
Daniel Spratt (Case Western University)
Introduction by Howard Soule (Prostate Cancer Foundation)
View the Transcript Below:
The Ongoing Legacy of Felix Feng Team Science
Howard Soule, PhD [00:00:12] Good morning. Once again, I’m Howard Soule from the Prostate Cancer Foundation. And this part of our scientific retreat is a little bit bittersweet. I think everybody in the room knows that we lost a giant in our field late last year, Felix Feng. We miss him dearly, but we want to keep his legacy alive and his immense loyalty to the field of prostate cancer science and patient care we just will never forget. So last year Dr. Beltran did this lecture, she was awesome. This year Dr. Dan Spratt is giving this lecture. So, for the three or four people in the room that don’t know who Dr. Spratt is, I’ve known him for a long time now. Dan went to medical school at Vanderbilt and did his residency in radiation oncology at Sloan Kettering. I first met Dan when he was on faculty at the University of Michigan, when we, I’ll give away part of my quiz question, when we named him a PCF Young Investigator. He has ascended greatness as a physician scientist. Many, many contributions to our knowledge of the field. Thank you for all of that. That body of knowledge, Dan. And he’s currently the chair of radiation oncology at the University Hospitals of Case Western Reserve and the Seidman Cancer Institute in Cleveland. And as I learned by text message this morning, Dan is also the associate chief science officer for the entire University Hospital healthcare system in Cleveland, so I have a quiz question. Mike Milken usually does quiz questions, but he spared us this year, so I get to do one. Who are the young investigators from our organization, PCF, that ascended to become chairpeople of radiation oncology departments? Anybody know the answer to that? Few of you probably do. So, here they are. Dan Spratt, Dan Hamstra, Kosj Yamoah, and Phuoc Tran, who’s the most recent inductee at MD Anderson Cancer Center. Four terrific individuals of immense intellect and have made gigantic contributions to the field. But one that stands out in all of our minds and hearts is Felix. Because it was Felix that, on a trip of mine to the University of Michigan, sat me down in a little conference room. Already Felix was introducing the next generation of radiation oncology physician scientists that turned me on to Dr. Spratt and Dr. Hamstra. I’ll just, I’ll never forget the experience. It was absolutely mind blowing. And so now we ask Dan to come to the podium and to share his thoughts as the ongoing Felix Feng Legacy Speaker of 2025.
Daniel Spratt, MD [00:04:00] Thank you. Appreciate it. Well, thank you, Howard. Thank you, Andrea. Thank you, guys, so much. Definitely bittersweet to say the least, but something I’m incredibly proud of. As Howard said, if there’s someone who doesn’t know who Felix Feng is, we can talk after. But he probably has had one of the most colossal impacts on this field and definitely my own career. So, Felix Feng, unfortunately, right, he didn’t quite make it to 50 years old. He passed away last year in December. But he has an impact that is felt, you know, globally around the world. He is someone that I reflect on. I recently started reading Marcus Aurelius’ meditations and it is a basically reflective piece. And it’s really been something that as Felix was going through some of his last, what we’ll say six months of life, we sort of developed a very different relationship and it became a much more introspective relationship and it’s something I continue on to this day. We talk often, you know, when we’re not thinking about life and death and we think about what’s impact, people look at these types of numbers which is not why Felix did what he did, but at someone under 50 years old to have over 500 publications and these are not just any publications, these are practice changing work. It’s pretty remarkable and that last bar there is 2025. So how many of you published 30 papers after you’ve deceased is pretty incredible and that will continue. You know, while he has incredible amounts of grants here, you know, tens of millions in funding, I would say what he will, no question, be most proud of is the 3,200 collaborators, co-authors that he has, almost half of which are international. It’s just truly astonishing. I am not gonna list 3,200 people here, but you get the point. Many of them are in this room. There’s dozens, countless of videos, pictures of the impact that he has had. And this is the title of the talk. This will be the ongoing legacy. All of you, all of the trials he started, all of companies he started. All of the grants. How we will pass on to future generations. This will be Felix Feng’s legacy. So, who the heck am I to talk about Felix? This is a giant, as Howard said, in the field. It’s a big responsibility. Misha did an incredible job last year. So, I knew Felix for about 10 years. We have a very interesting relationship. I’m a complete, despite what many of you may think, a complete introvert. Felix is an extrovert. He’ll stay out till late in the night, I retreat back to my room. But we just worked incredibly well together and were able to accomplish a lot. So, I met him in 2014. He was at University of Michigan. And he helped recruit me to University of Michigan and he and Mary left to UCSF where Mary still is today. And I, as Howard said, I was at Sloan Kettering and so there’s actually only seven months we overlapped. So, what does this overlap really mean? How much can he have an impact on someone? I think for most of us, if there was a faculty member we worked with for seven months, It’s probably a blip, not something you would think much about, but this has been sort of what I’ll show you today. I think we’ve been able to accomplish a lot that’s going to continue to change the lives of millions of people. And so going back, I would never be someone to ever brag about how many papers I had except when it comes to Felix Feng, because this is what I will still, to this day, And I will, if anyone here works for JAMA Oncology. They made me remove Felix on a paper two weeks ago because they said he didn’t review the paper, so shame on JAMA Oncology. But this is something that about one out of three papers Felix did since I met him, we collaborated on. And so, it was really special what we were able to do. And this is to have an impact on patients. And so, while you’ll hear about the incredible basic science that he has done, what we really focused on is the translational and clinical trials and really clinical implementation to change practice for patients in front of us. And so, you know, when I first met him, you know there’s like many, many people were developing all these gene expression signatures. People had protein stating, KI67. It just seemed like another fad, but he had a vision of how do we really make prostate cancer look like other cancers? How do we incorporate transcriptional testing into our day-to-day practice. And if you fast forward a decade, and this is an ungodly, almost uncomprehendable amount of work that has now validated this test in 14 phase three randomized trials. Many of you have been part of this work from localized disease to castrate-resistant disease, metastatic disease. If you think of the Oncotype Breast Test that has been used by over a million women, it only was tested in a few clinical trials. And so, this body of work, and most recently this year, congrats to the STAMPEDE team and everyone involved, privileged to even be a part of this, is this continues to live on. So, this cell paper that just came out looking at how transcriptomic testing, and really the Decipher test, is able to predict treatment sensitivities in reasonably aggressive to advance prostate cancers and how we can use this clinically. But what else you see on here, and I highlighted this, the ARA activity, that’s a collaboration. Felix introduced me to Ed Schaeffer, who’s out of Northwestern, and we developed this ARA Activity Signature. And many of the signatures you see on here are collaborations from Felix Feng. Some of these, as I’ll talk about, are in clinical development to be used. This, again, I’m sure people at Veracyte can correct me, I think it’s been used in over a quarter million people. I think this year they’ll use it in over 100,000 patients clinically. So, talk about impact. And there is the gold standard that we have lagged behind. You know, Dr. Hussain just showed us using BRCA mutations from PROfound. That’s a prospective biomarker stratified trial, right? We don’t have these historically in prostate. We have all this retrospective data. Two trials of almost 5,000 people, the top ones already fully accrued. We will have now true biomarker directed to redefine how we think of prostate cancer prospectively. Moving on, George Zhao was a resident, you know, so it’s funny, I see George here, and you know we were teaching George how to circle prostates and contour them for radiation, and amazingly, work that again, I think none of us thought was gonna actually translate really and really work. I don’t wanna say it was purely academic, but George and Laura Chang, Felix, myself helped develop this signature called a PORTOS signature trying to see we want to limit the use of radiation. We want to limit the use of any therapy that’s not helping a patient and this signature again retrospective data I’m the biggest critique of my own work in that this should not be practice changing. No one should use PORTOS at this stage And I hope no one did up until this point, but it looked like we could identify subsets that really benefited from radiation and over the next, working with Felix, we got tissue access, we had to submit basically grant applications to the NCI to CTEP to profile tissue. This is now both in trials from the United States as well as in Europe has profiled and these are post hoc analysis of randomized data that we can identify a subset of patients that if you give them higher doses of radiation, you provide a profound benefit, but those with a lower PORTOS score, you don’t need that extra dose, which causes toxicity. This will be in the next large, multi-thousand patient phase three trial, tested again in a prospective randomized trial to get level one evidence to redefine how we are gonna personalize using radiation therapy for patients. I won’t talk as much about Artera because Andre Esteva is gonna be having a whole talk in a little bit about this. But just to say, the work that we had learned from all of our collaborations on everything previously was able to catapult to really make Artera start with a bang in jumping straight into profiling now about a dozen randomized trials. It’s a digital pathology based multimodal imaging platform. And it’s now already, it’s Karen Hoffman. There’s a smaller trial out of MD Anderson, but a trial that’s now already using this to help personalize the way that trials are being done to treat patients. And what I’ll spend a decent amount of time on, which was just presented less than a month ago at our national meeting, this is probably the most exciting project I’ve had the privilege to be a part of that was designed with Felix. So, Felix was the co-PI of this trial with me. And we got the results of this trial one week after Felix passed. And I will say this probably multiple times, I think this is probably one of the biggest discoveries that we will have had in many years, I’ll talk about. But PAM50 was another kind of project, I was just talking with George, that we almost were like, ah, this is like stupid. We’re taking breast cancers PAM50, they had five subtypes, we’re gonna knock off the HER2 subtype, the normal-like subtype. We’ll apply it, we’ll make a paper, and we can show luminal B patients seem to benefit from hormones therapy, beta-like patients don’t. Whoop-de-doo. But maybe it’s gonna work, right? Because there’s zero predictive biomarkers for hormone therapy. You go back to Huggins 1940. We don’t have still today, 80 years later, a single validated biomarker to tell us who to give hormone therapy or not that’s been validated in a dedicated biomarkered directed trial, zero. That’s, I would say it’s embarrassing. It’s unfortunate, right. And so, we tested this, and this was one of the plenary presentations at our national meeting. It’s called the NRG GU006 trial, or the BALANCE trial. And it’s a double-blind, placebo-controlled, randomized trial of men with recurrent prostate cancer. Underwent surgery, they had a detectable PSA. They had prospective testing of PAM50 and were stratified, importantly, similar again, kind of going back to the PROfound trial. You’re either going to be biomarker positive or negative. In this case, it’s luminal B or non-luminal B. And you’re randomized to placebo or six months of apalutamide. So, this is kind of similar, it’s a hierarchical design where you first evaluate in the biomarker positive patients, that’s the luminal B, if they benefit, then you gotta see does this biomarkers work? You test in the biomarker negative. If there’s no benefit, then you just pool it all together and you ignore the biomarker. And the primary endpoint you can see is biochemical progression free survival, that’s a composite endpoint of a biochemical recurrence, local, regional, distant mets or death. And secondary endpoints, one of the key ones being MFS, which as all of you know is a surrogate for overall survival. These are just the patients. These are your normal patients that have recurrent prostate cancer after surgery. Most of them have a low PSA. You’re catching it early, but half have positive margins, half have pathological T3 disease. 43% were luminal B, 38% were basal-like. And if you look on the Decipher which predicts metastatic risk, over half have a high or very high Decipher score. So, these patients have bad biology. So, this is it, right? So luminal B, we’ve been waiting for this, took a decade to get to this point. Luminal B patients, if you add six months of apalutamide, improved biochemical progression free survival by 18% at 5 years. The haz ratio of 0.45. And very importantly, is this really a predictive biomarker? In the non-luminal B subset at five years, which is the median follow-up, there’s identical five-year point estimates. The haz ratio is effectively one, and of course, non-significant. And probably even more powerful is MFS, which would be, again, the endpoint any phase three trial would be using. There’s a 13% improvement in MFS with adding apalutamide in luminal B patients. Has a ratio of 0.27. In the non-luminal B, the curves are completely superimposed. Same five-year point estimate has a ratio of one. This is about as big of a slam dunk that going back to Michigan with George being a resident and Felix, we never thought this would be as wildly positive as it is. Apalutamide, you guys know the side effects, a little bit of rash, a little bit of hypertension, overall, very well-tolerated. Modern radiation therapy on this trial, we’re talking about single patients that had grade three toxicities. So, it’s gonna be very hard to beat radiation therapy as a safe salvage therapy for these men. So PAM50, let’s put this in context. It is the first and only biomarker that’s validated to predict hormone therapy benefit in any disease state of prostate cancer, period. I’m not saying this works in every disease state, but it’s the only one that has been done. It’s also actually the first and only gene expression test across all of cancer to be a predictive biomarker. And some of you will say oncotype for breast. It actually did not validate in TAILORX and Responder X [RxPONDER] in their prospective trials as a predictive biomarker. And we can chat after, if you’d like to, about that. And this is now gonna define a new way of categorizing prostate cancer. We think of breast cancer, you define it as ER positive and they have their trials. You have HER2 positive, you have triple negative. We now finally can categorize these patients because now how the heck do we treat non-luminal B patients and we’ll need dedicated trials. So, this is, in just one realm of the world that Felix touched, that I was fortunate enough to work with him on, that is going to continue his legacy for years to come. I miss Felix tremendously. I feel his absence in so many of the roles that I have. And this quote, many of you have seen from him, I think is so true. “The magnitude of what we accomplish is not measured in just what we have done, but measured in terms of the kind of collective efforts of everyone that you’ve helped along the way.” He has had a great impact on my own career. And so, I stole this from his, that’s Mary, his wife, stole this one of the videos that’s been put out, the many things to commemorate him. And so, thank you, of course, to Felix. Thank you to PCF. This is just a short list of people that have been involved in the work I’ve showed you today. And thank you all for being here.