They based their "expanded-use" approval on the PSMAfore trial. In addition to mCRPC, men had to:
• have tried one ARPi (Zytiga, Xtandi, Erleada or Nubeqa)
• be PSMA-avid on a PSMA PET scan
The trial compared radiographic progression-free survival (rPFS) of Pluvicto to a switch to a second ARPi. In the trial with 2 years of follow-up, median rPFS was 11.6 months vs. 5.6 months. There was no statistically significant difference in overall survival.
Thank you for posting this. It's very important to get direct references to the latest information. Because most of the time lay people are getting their information from popular journals. Or doctors who may or may not be quite so up to date. Direct from the source can make a difference. This is a huge service.
In this context, I would be grateful to understand what all this means in terms of improved outcomes. There's always a lot of buzz about exciting new technologies that promise improved outcomes. But it always bothers me that during the last few years that I've been reading about this, that improvements from a new therapy is almost always only a matter of months and usually not even close to a year.
Case in point: Assuming one's prostate cancer is PSMA avid "There was no statistically significant difference in overall survival." Although apparently this therapy gives us about 6 months extra rPFS ("radiographic progression free survival").
So far I'm doing okay in a sort of steady-state of doublet therapy (and with chemo earlier) for metastatic prostate cancer-supported health. 36 months from diagnosis. Am I missing something? Six months of rPFS, and no difference in overall survival, doesn't seem very attractive by comparison?
We see so many headlines in popular general media or popular health media, or even professional health media, about some new fancy therapy. And it turns out that you get "six more months" etc. I'm sure if my back was against the wall I would treasure six more months with my family, my wife and daughters!
Apparently some of these new therapies are well tolerated, but even what would be the quality of life in that last 6 months anyway?
If I put on my cynical hat, I would think that men who are desperate for more time with their loved ones, probably all or most of us, can be persuaded to become guinea pigs for vastly expensive therapies. Even FDA approved. The phrase "moral hazard" comes to mind. I won't even mention lazy journalism. But now I will take off my cynical hat.
Let's look at a critiques from within the medical community of this phenomena. From 2022, not so long ago, the year I was diagnosed, and from what seems like a high quality publication:
Marginal Benefit in Overall and Progression-Free Survival from New Anticancer Drugs
"However, overall survival (OS) and progression-free survival (PFS) were only prolonged by a median of 2.80 and 3.30 months."
Some of these new therapies are crazy expensive. Aside from even the questionable benefit, what is the opportunity cost? Public or private health insurance institutions are paying for one thing, and but not paying for another thing. Consider underfunded patient frontline services. For example, diagnostics are tightly rationed in Canada. Maybe we would have more budget for more diagnostics that would enable fine-tuned therapies. Or maybe even limit over diagnosis? Or fund PSA tests!
And what about the research opportunity cost? All this nuclear therapy research is usually expensive and I suppose exciting for physicists and machine builders, but that means that there is less budget for hormone therapy research.
The "let's kill cancer" crowd seems to own the field (along with, in fairness we should say, the genetics crowd). As opposed to "let's understand the fundamentals going on underneath", especially at the level of body system-wide hormone ecology. Can we say "Let's see if we can turn prostate cancer into something chronic"? Because as it stands metastatic prostate cancer is always a terminal diagnosis. No matter what the heck we do it, killing it doesn't seem to have been successful, at least when we go metastatic.
As I said, I would be happy with 6 months extra with my family. But I'm kind of trusting the medical system that the choices offered are reasonable and wise. I'm not sure that trust is warranted.
You have to look at the outcome a study is powered to determine. The PSMAfore trial was only powered for rPFS, which is reasonable for an expanded use trial. It is possible that with a larger sample size and longer follow-up, there might be an OS benefit.
No, it would not be great. It would mean that patients would have to wait longer which may be too late for some), and many trials would fail to accrue. Prostate cancer, unlike other cancers, takes many years to be fatal, and by the time results are in, there are new medical technologies, so results might be irrelevant.
Wow. Thank you for the clarification, a welcome disillusionment even. (FYI I added a slight clarification to my own reply earlier, just to make sure we don't have a misunderstanding on what I thought I was being positive about.)
In my reply, I was trying to interpret what you said, positively, and I think any lay person would probably have the same positive reaction. Sort of "more research could possibly show that there is a real and significant benefit to this therapy". That sounds like a good thing.
"There could be already a real benefit, although the implication is there isn't. But there might be."
But in reality, from your new reply, in the meantime for this therapy, all we have is rPFS extension of 6 months. And no change in OS. Am I being churlish saying this doesn't sound like very much?
But that's not the point of your new comment I think. Your new comment seems to be saying "we shouldn't bother waiting for bigger trials concerning this therapy. Because they will take too long for people who don't have much time". And you even hinted that there are more therapies in trials which also could take years to confirm. And let's not forget that a trial is a trial. An outcome could be "it's not worth pursuing". It's a waste of time. It's not helping our patients. They died. (From participating in PCa communities and even in dialogue with healthcare staff, I've noticed a kind of "get on a trial" meme. In fairness and according to trial ethics, people never get less than the therapies they are on now or standard of care therapies now. But as I mentioned elsewhere, there is research indicating that medical trial participants aren't especially better off for that.)
Popular understanding of statistics sometimes can be misleading. And again the moral hazard. And this shows up in forums as to what can only be described as advocacy for leading edge therapies, other words therapies that are already approved and out of trial.
So what about approved new therapies? As addressed in your reply? And where they are powered only for a preliminary endpoint such as rPFS? And apparently it's not a good thing to wait for a big trial to prove (or not) OS. Because in the meantime, time is lost. My original long post above highlighted the opportunity cost. I think this is exactly the same thing that you are expressing as "by the time results are in, there are new medical technologies, so results might be irrelevant". The opportunity cost is high!
At this point I'm left with I kind of nihilism. Nihilism is terrible. There are trials and there are trials. The giant RCTs that delivered the knowledge which were the basis of the therapy decision making that has given me so far 3 years are one kind of trial. However, it sounds like there are other kinds of trials that don't contribute to the progression of science and knowledge. Based from moral hazard they are noise and delay.
But where does this leave the participant in this forum? Some people like to say that "every person is different", as a sort of an excuse for something. I think that's kind of nihilistic in and of itself. Medicine exists because we're all living in human bodies. And we all share a lot. Although dysfunctions may progress in different ways, and we would like to have physicians that are sensitive to nuance.
But ADT works for almost all of us with prostate cancer. From beginning to end apparently. That's a positive thing. It's something we share!
So what can be the positive rubrics or decision making templates that can help someone as a participant in this forum? It would be worthwhile to have a mini-forum on this topic.
An example of a topic on such a forum could be "how to avoid therapy hype, with clues on which therapies are not worth waiting for" or "is it worth doing some unproven therapy if you get a claimed 6 months LE extension, or just rPFS extension" or "what does a 43% decline in mortality mean?" These are all negative things but maybe there can be positive things too.
Exercise is easy to say but hard to put into practice. "What about the balance between aerobic and resistance? What about getting enough protein? What about micro shocks in exercise to strengthen the skeleton? What about recovery if you enthusiastically over exercised? What are safe exercises if you have skeletal mets?"
And more generally what are the families of therapy that we should be focusing on as opposed to overhyped therapies? I'm not even fully sure about such a dialogue. But it seems that there is a need for something like this. And to be positive in a productive way rather than just bouncing around like a cork in the ocean all alone.
Full disclosure: apparently one shouldn't apologize or explain. And yeah sometimes I write long replies. (It's an interesting misunderstanding in the world of sales and marketing that short copy is the only thing that works. And that long form is a disaster. And this misunderstanding sometimes just turns up as "never write long form". It's a welcome message in a world where people are losing the ability to read books and long articles even. Nevertheless the truth of the matter is that for a given article or post or whatever that reaches an audience, even a targeted audience, maybe 90% or 95% or 99% of people will read the first paragraph and not go any further. So from that naive perspective it's a failure. But the 1% or the tiny percentage of people that read a long item, it could be great. Because it's relevant to them. And if it's really relevant and they're attracted by the beginning of the item, they will want more. More analysis, more proof, more plans for action etc. I think it's the same even here. Some people think I write long items. That's fine if they're not interested. But I know a few people that have found longer items worthwhile, because it speaks to them.) so anyway, full disclosure. I don't know if this long item is of interest to anyone, but I just had my 28-day Firmagon / Degarelix injection. By the specialist nurse. The injection was perfect and the site is fine, just a little sore. But I got my usual 24 hours plus of 2° C elevated temperature, and paradoxically severe shivers. (Never hot flashes.) At the peak, I experience severe body weakness that lasts for about 4 or 5 hours, and I'm at risk of falling. I don't know if that's something to do with mitochondria or whatever? And I just put on six blankets because I'm cold. Sleep for 12 hours. And then everything gets better. Not a bad price to pay for 3 years so far. Also I got cabin fever and felt the urge to share. LOL. 😃
You may want to learn what is meant by the term "power" before you write another long response. I'm sorry I don't have time to read them, but when I see that a patient has an essential misunderstanding and is only expressing his confirmation bias, there is really no point.
I'm pretty sure my use of the word "powered" is correct; I was kind of quoting you. rPFS is a preliminary endpoint. A trial designed to confirm or not a hypothesis concerning a preliminary endpoint or any given endpoint for that matter is power for that, by definition.
And you said in this context that "It is possible that with a larger sample size and longer follow-up, there might be an OS benefit." My confusion started when I replied positively considering this possibility.
And your answer was "No, it would not be great. It would mean that patients would have to wait longer ..."
This is a profound statement and very important. But not easy to understand. I think you were making a strong criticism of current drug development and adoption policies.
As for confirmation bias, I can't imagine what that would be. I am more trying to find good things to confirm. I do have a prejudice against poorly justified and over-promoted medical technologies.
rPFS is the PRIMARY endpoint, not the PRELIMINARY endpoint. It means that the trial is powered to detect (could reliably detect) differences in rPFS that make it statistically non-inferior. However, because overall survival (OS) was a secondary endpoint, it was not powered to detect that endpoint.
You replied that you wished that the primary endpoint should be OS :"That would be great if there was. And for meaningful longer timeline." A meaningfully longer timeline would mean that patients would have to wait several more years to get Pluvicto earlier. I was not making "a strong criticism of current drug development and adoption policies," I was criticizing your critique. This misreading is a prime example of your confirmation bias. You are so convinced that the trial is misguided, you cannot see that it was done well.
It looks like I used the phrase "preliminary endpoint" in a more general sense than one specific to the context of the trial. (Apparently I'm okay on "powered" now.) I was thinking about endpoints from the patient's perspective I guess; from our big picture patient perspective, some RCT primary endpoint conclusions are just that, "preliminary". Considering these are matters of life and death, that denotation is useful . And apparently legit:
"Progression-free survival (PFS): PFS, which measures how long a patient lives without their cancer progressing, is often used as a preliminary endpoint because it can be assessed earlier than overall survival."
Be that as it may, these endpoint terms weren't even used in our original short dialogue together. From that dialogue, I felt you had shared a deep insight with a lot of implications. But it was kind of hard to understand. And so I explored them, including the questions of opportunity cost and moral hazard. You might not be comfortable with the direction I took, which is fine. I did appreciate the almost provocation that invited a response.
As for the trial itself, I'm sure it was done well. I never questioned that. I did question whether the results so far should be anything to be excited about. "No difference in overall survival" doesn't sound very good.
""No difference in overall survival" doesn't sound very good." You still don't understand power. Power is the ability to reject a false negative (e.g., there was no effect on overall survival).
You also refuse to understand why rPFS was used here, but I am tired of explaining.
Excuse me for interrupting but I'd like to share some information that might be helpful. A research scientist/professor named Thomas Seyfried has a protocol which involves starving cancer of it's 2 fuels; glucose & glutamine. The dysfunctional cancer cells have reverted to fermentation...they can no longer use oxygen AND they can't use ketones. Our healthy cells thrive on ketones. Seyfried is blitzing various health-related YouTube channels with interviews explaining his protocol & success stories. Guy Tenenbaum applied Seyfried's protocol (stage 4 metastatic prostate cancer) with great success (look his name up on YouTube). Pablo Kelly lived over 10 years with glioblastoma...brain tumor. Then, do a search for Dr. Makis' fenbendazole & ivermectin protocol that has many success stories. You'll also find Joe Tippens' miraculous comeback from stage 4... he heard about fenbendazole getting rid of cancer in animals and so he started taking it... it eliminated his cancer! So, there are many very hopeful things being applied RIGHT NOW that don't involve the big money monoliths of $Big Pharma & Big Health"care". If they can't make tons of money, they don't want it. I am applying a combination of the above protocols.
Seyfried makes big claims. But there are no human trials to back them up. And it's impossible to implement. Because you can't practically get rid of glutamine in your body without glutamine antagonist drugs. Wanna be a guinea pig?
Consider that the same complaints one might have about big pharma and institutional medicine, including moral hazard (i.e. corrupting profit motivation), poor or faddish investment choices, objectification of patients or just plain incompetence etc., absolutely also apply to the world of alternative health. Plus less regulatory oversight!!
Very interesting thread. Thank you for the analysis. I am still watching for a trial that does up front Lu-177 on metastatic hormone sensitive prostate cancer and then straight into Docetaxel which is the order I did it in. I am not spending as much time reading the trials as I once did but don’t think one is happening. If it is I’d appreciate a direction.
I really tried to get accepted for PSMAddition but in hindsight am pleased I didn’t. I really didn’t want to go near Docetaxel at that early diagnosis with no symptom stage but in hindsight am pleased I did.
To me this order, early on is worth investigating but I definitely am biased as of course I’d like to know.
Any trial on mHSPCa doing 3x Lu-177 into 3 x Docetaxel?
Unlike many people I try to refrain from worshiping randomised clinical trials as some king of gold standard.
The pharmaceutical companies that fund most of these clinical trials, often set up biased study designs, selective reporting, and suppression of negative results. After all, they have significant capital invested and at risk in whatever drug or intervention they are studying.
The FDA and other regulatory agencies often focus on checking procedural boxes rather than critically assessing whether a drug or intervention provides real-world patient benefit.
To blindly accept that these trials are the highest level of evidence in my view is perhaps one of the biggest impediments to the practice of modern medicine.
The influence of the funding and commercial imperatives needs to be minimised if not completely eliminated.
Observational studies, case reports, and real-world evidence should be included more often rather than be dismissed as they may provide valuable insights that RCTs miss.
Any drug or intervention that truly benefits patients should demonstrate clear, meaningful clinical improvements rather than relying on arbitrary p-values or surrogate endpoints.
True patient benefit should be evident in real-world health outcomes—such as improved survival, quality of life, or reduced disease burden—rather than statistical thresholds or indirect measures that may not translate to actual patient well-being.
Science gives large, well-done randomized clinical trials the highest level of evidence (level 1). Even higher if it is repeated (Level1a). I follow science.
There are rules for FDA approval that avoids all of the potential problems that you imagine are prevalent.
I agree that most Big Pharma-funded clinical trials use a SOC in the control group that give the best possible benefit to the new drug. For example, the PSMAfore trial could have used docetaxel in the control group. It is silly to say that drug mfrs should not fund their trials -- if not them, then who would pay for them? I think IRBs on the whole do an excellent job on the ethical front.
For a non-inferiority trial, like the PSMAfore trial, a hazard ratio proving it is not inferior to the SOC is certainly the real world result patients require. Remember, this is only an approval for an extended use of an already-approved drug (and Pluvicto is already available off-label to patients who can pay out of pocket). This approval opens the way for Medicare/insurance to cover it.
They used rPFS instead of OS to get faster approval for its extended use, since Pluvicto safety is already well-known. Would you prefer that patients would have to wait another 5 years to get OS as a primary endpoint?
I agree that well-conducted RCTs are a cornerstone of evidence-based medicine. My concern, however, is that commercial interests can subtly influence trial design, potentially leading to a focus on endpoints that might not reflect true patient benefit. While I understand that the FDA has safeguards in place, I feel that the financial incentives behind trials can sometimes skew the findings or how they are presented.
Regarding surrogate endpoints like rPFS, I understand their role in speeding up the approval process, but I still believe that long-term, real-world data is crucial for understanding whether these treatments truly improve patient outcomes. I appreciate your perspective on this and think it’s an important issue to continue discussing, especially as we strive for a better balance between speed and thoroughness in approval processes.
The language you use is the language of conspiracy theorists: "concern... subtly influence,""feel...can sometimes skew." I hope you don't continue on this path. It is dangerous to your health.
Don't worry. There is always real world data collected after approval.
Dismissing legitimate concerns about industry influence in clinical trials as ‘conspiracy thinking’ is not a serious argument—it’s an attempt to shut down discussion. Skepticism is not the enemy of science—blind faith in flawed systems is.”
It is not "legitimate concerns" when all you express are "feelings." Legitimacy must be based on facts, not feelings. When you have some facts, we can discuss. BTW- I believe science is always provisional. I do have open-eyed (not "blind") faith that science will give better answers than your inchoate feelings.
If you believe science is provisional, then you should also acknowledge that questioning how studies are designed and funded is part of that scientific process. The influence of commercial interests on clinical trials is not a ‘feeling’—it is well-documented in the medical literature. Selection of endpoints, trial populations, and reporting biases are real issues that have been extensively studied. If you’re open to discussing facts rather than making assumptions about my position, I’d be happy to do so.
"Feeling" is the word you chose. So, do you have any actual criticisms, other than your feelings, of this trial? What are they?
" Selection of endpoints, trial populations, and reporting biases are real issues that have been extensively studied." The fact that they are real issues that are already considered is the opposite of what you allege - that they have not been considered.
So we agree that selection of endpoints, trial populations, and reporting biases are well-known.
My point is not that these problems were ignored, but that they are persistent challenges in clinical trials, including the PSMAfore trial, which can still impact the interpretation of the results. There is often variability in how effectively these issues are managed.
The fact that they are “considered” doesn’t mean they are always fully mitigated or transparently reported in the results.
Despite efforts to account for these biases, they remain inherent in many RCTs, especially when there’s financial conflict of interest or pressure to present positive results.
Acknowledging a challenge does not always equate to resolving it, and the real-world impact of any trial is shaped by how thoroughly these issues are addressed.
To your question of my actual criticisms of this particular trial there are several aspects of the study design and reporting that warrant further scrutiny. Issues like endpoint selection, patient population representativeness, and potential reporting biases raise concerns about the trial’s overall reliability. Additionally, the use of surrogate endpoints and the relatively short follow-up period may limit our understanding of the long-term clinical implication.
"So we agree that selection of endpoints, trial populations, and reporting biases are well-known." No, we do not agree to that. I agreed that "Selection of endpoints, trial populations, and reporting biases are real issues that have been extensively studied." My point was that the investigators of the PSMAfore trial have studied those things and are adept at avoiding those issues.
You say these issues continue to be flaws in the PSMAfore trial, yet you fail to demonstrate your point. Is it possible they were all addressed already? People a lot more experienced than you put this trial together. If there is a flaw, point it out instead of clinging to vague generalities. I pointed out a flaw, have you?
"To your question of my actual criticisms of this particular trial there are several aspects of the study design and reporting that warrant further scrutiny. Issues like endpoint selection, patient population representativeness, and potential reporting biases raise concerns about the trial’s overall reliability. " Like what? Again, vague generalities. Specifically, which endpoint should have been used? Which patient population? what is biased about their reporting?
"Additionally, the use of surrogate endpoints and the relatively short follow-up period may limit our understanding of the long-term clinical implication." These are addressed by the researchers. It is a "new indication" trial whose purpose is to find whether earlier use of an already-approved medicine is warranted. The FDA allows different endpoints for new indications. The trial only has to prove the medicine is useful in some way for the new use. It is not necessary to "reinvent the wheel" by proving efficacy and safety as it did in the VISION trial. The clear patient benefit is to give patients choice for the new indication. If that is inadequate for you, you are free not to choose it.
The fact that selection of endpoints, trial populations, and reporting biases have been studied does not inherently mean they were successfully mitigated in the PSMAfore trial. Recognizing these as challenges is not the same as assuming they were flawlessly addressed.
You ask for specifics, so let’s start with endpoint selection. The trial primarily relies on radiographic progression-free survival (rPFS) rather than overall survival (OS) as its primary endpoint. While rPFS is a valid measure, it is a surrogate endpoint, and its correlation with actual patient survival and quality of life is not always straightforward. Given the nature of this treatment, a more robust long-term outcome—such as OS or even patient-reported outcomes—would provide a clearer picture of real-world benefits.
Regarding trial population, the exclusion criteria and patient selection process can shape outcomes significantly. If a trial population is not fully representative of the broader patient group that will eventually receive this treatment, the results may overstate the benefits or understate potential risks. Were patients with specific comorbidities underrepresented? Were there limitations in racial/ethnic diversity that could impact generalizability?
On reporting bias, we need to ensure that adverse events and limitations were not downplayed, even unintentionally. Were all key secondary endpoints reported with equal transparency? Were any analyses conducted post hoc that may have introduced bias? These are fair questions when critically assessing any trial.
As for follow-up duration, while I understand the rationale for a shorter study period, the concern remains: how confident can we be in the long-term durability of benefit and safety profile when follow-up is relatively brief?
So no, this is not about vague generalities. These are real and reasonable concerns about how trial design influences conclusions. If you believe these issues were all sufficiently addressed, I’d be happy to see the specific data or rationale you’re relying on to reach that conclusion.
You misunderstand the context of the trial. It was done AFTER the VISion trial that did use OS as primary endpoint. As I've explained several times aand you fail to acknowledge, this was only an expanded use trial, so it did not have to prove the OS and safety benefit again. It was not a surrogate endpoint, it was the primary endpoint for expanded use.
"Were patients with specific comorbidities underrepresented?" No.
" Were there limitations in racial/ethnic diversity that could impact generalizability?"No
"we need to ensure that adverse events and limitations were not downplayed, even unintentionally. Were all key secondary endpoints reported with equal transparency? Were any analyses conducted post hoc that may have introduced bias? These are fair questions when critically assessing any trial." Who's this "we"? The researchers did all of those things. Why would you simply assume they hadn't? Read the detailed study instead of making up strawman arguments.
Strawman arguments like these make me believe you are not serious and and you are wasting my time.
My original post was driven by a personal frustration as someone living with prostate cancer. This is not just about clinical trials or data—it’s about the real-world experience of living with a disease that doesn’t wait for ideal solutions. As a patient, it’s disheartening to see treatments focus so heavily on late-stage cancers when I, and many others, are left wondering why more isn’t being done for earlier-stage interventions.
I raised concerns about transparency and bias because, as a principle in clinical trial evaluation, they are critical to understanding the validity and applicability of findings.
Lack of transparency and bias along with the relentless “publish or perish” culture within academia and the medical industry can potentially impede running parallel early and late-stage studies.
I just wish for a system where we can ensure that the research landscape is not unduly influenced by external pressures or conflicts.
To our discussion:
You are stating that the researchers have already addressed these elements in the PSMAfore trial.
I can only assume that as a man who believes in science you are relying on specific data or some rationale that allows you to state this.
If this is true, then clearly one could argue that the trial was productive in advancing medical research, especially for patients with advanced prostate cancer.
So there’s no reason to as you said …..waste your time……by unnecessarily reiterating my concerns in this specific case.
We need to ensure that cancer research isn’t influenced by commercial or publishing imperatives that lead to trials that are just designed to generate results that are easy to market.
If the same resources used in the PSMAfore study were directed toward tandem early and late stage interventions we could gather evidence more quickly, potentially speeding up the approval process for broader indications. This is particularly critical for cancers like prostate cancer, where early intervention could significantly impact patient survival and quality of life.
Question is what determines how resources are used?
Many patients share your ignorance about why clinical trials are done for late stage cancer patients first. It is also natural, faced with so many unknowns, to just make up answers in your ignorance, rather than doing the hard work of finding out the real answers. Unfortunately, arrogance blocks edification.
You are at the stage of the Dunning-Kruger Curve that some on the Internet call the peak of Mt.Stupid. I prefer the term agnorant - a neologism of ignorant and arrogant. The only cure is humility. Good luck!
Your response is pure condescension and empty arrogance. Instead of offering a thoughtful rebuttal, you resort to juvenile insults, which only highlight your inability to engage in an actual discussion. That’s not intelligence—it’s insecurity.
Let’s be clear: questioning research priorities is not “ignorance.” It’s critical thinking. The fact that you’re so offended by the idea that patients deserve answers about why trials are structured the way they are says everything about your approach to discourse—and none of it is good.
You can throw around insults all you want, but it won’t change reality: commercial interests, institutional inertia, and regulatory frameworks influence which studies get funded and prioritized. If you refuse to acknowledge that, then you’re the one ignoring the bigger picture.
I don’t waste time arguing with people who mistake arrogance for expertise. If you have a real counterpoint, present it. Otherwise, don’t expect me to take you—or your condescending attitude—seriously.
While you have accused me of ignorance, I wonder if you would send the same condescending response to the following experts, who have publicly questioned the way clinical trials, especially in cancer, are designed and prioritized:
Dr. Siddhartha Mukherjee, an oncologist and author of The Emperor of All Maladies, has long discussed the need for a shift in focus toward earlier-stage cancers, arguing that the emphasis on late-stage treatments often overlooks the significant potential for preventing severe disease through early intervention.
Dr. Peter Bach, Director at Memorial Sloan Kettering, has been outspoken about the commercialization of cancer treatment research and how this prioritizes high-profit late-stage treatments over early-stage interventions that could ultimately save more lives.
Dr. Gary Schwitzer, the publisher of HealthNewsReview.org, regularly critiques the reporting of clinical trial outcomes, particularly in cancer. He highlights how the framing of research results often serves commercial interests, not patients, and advocates for clearer, more accessible reporting that emphasizes meaningful outcomes.
Dr. Marcia Angell, former editor-in-chief of The New England Journal of Medicine, has been a strong critic of the pharmaceutical industry’s influence on clinical trials, including the focus on late-stage disease treatments at the expense of early-stage opportunities.
Oh but I forgot…….Your not going to provide any more thoughtful responses.
I never said there weren't issues about clinical trials in general that are worthy of study. All scientific proofs are provisional until proved otherwise. This post is just another straw man from you ("Flood the zone with bullshit" comes to mind). I tried to get you to focus on the OP here. I addressed your concerns about this trial, but you continue to ramble.
You’ve now completely ignored the larger context of this discussion and resorted to dismissive tactics. My concerns are not about “rambling” or “straw man” arguments—this is about the real, pressing issue of how clinical trials are designed and the glaring lack of focus on early-stage cancer treatments. It’s not just about your one narrow viewpoint on this trial, and it’s disingenuous to pretend otherwise.
Your refusal to even consider the broader implications of trial structures—especially when respected figures in the scientific community have raised similar concerns—only highlights the problem with how these discussions are framed. It’s clear that this isn’t about the specifics of the trial, but rather a refusal to entertain valid criticisms that challenge the status quo.
I’m not here to “flood the zone with bullshit” as you claim. I’m trying to make a legitimate point, but you seem more interested in shutting down any conversation that challenges your perspective, even when the stakes are the health and survival of actual patients.
If you truly care about improving the outcomes for cancer patients, you need to stop framing every criticism as a personal attack and start considering the merits of why these changes need to happen. If you can’t do that, then I’m done wasting my time here.
Mr. Prostate, have you ever attended a FDA Oncology Drug Advisory Committee Meeting (ODAC)? There is a great deal of medical and Scientific rigor during the FDA review and approval of new oncology drugs. If you never have I would encourage you to attend one in person or virtually. It is a very enlightening.
I understand that the FDA Oncology Drug Advisory Committee meetings are rigorous and that there is a significant amount of scientific and medical expertise involved. There is some level of scrutiny that goes into the FDA’s review process. My concern, however, lies not with the rigor of the review but with the structural influence of pharmaceutical funding on trial design and the emphasis on statistical outcomes, sometimes at the expense of real-world patient outcomes.
I believe that while the FDA review is thorough, integrating observational studies, case reports, and real-world evidence could help provide a more holistic view of how a treatment affects patients over time, beyond clinical trial parameters.
Thanks. Not sure I would qualify but having had radiation and Provenge, maybe...think it's worth doing? So far PSA is coming down nicely following radiation. Plus PSMA last summer showed no Mets(!), contradicting six years of previous scans.
As someone who's family has been affected by pancreatic cancer (lost my mom at her age 66, my oldest son at age 41, all three of us BRCA2) and as someone who's been reviewing information for at least 9 years (when I entered a pancreatic cancer screening program), I learned to look a bit deeper into study "results". Lots of study headlines would report something such as a 50% longer expected OS with the new miracle drug"(s), when in fact the OS might have gone from 4 months up to 6 months. Really? We are supposed to do cartwheels with the extra few months? Anyway, so thankful that past research and past clinical trials have helped keep me stable three years into my diagnosis of incurable Stage 4 metastatic Prostate Cancer, and so thoroughly disappointed with the proposed 57% budgetary reduction in the Congressionally Directed Medical Research Programs, as some of the life-saving medicines that are keeping me alive came out of that program's research. Thinking selfishly, I think there are enough "quivers in the arrow" left to keep helping keep me alive and functioning for a while, but I want future generations to be helped even more than all of us. Stay safe and healthy warriors.
They always start new drug clinical trials in the sickest patients to get faster FDA-approval for those most in need. Most drugs work better if used earlier and in healthier men, but trials have to run longer to get results. For example, docetaxel got approved fairly quickly for mCRPC men who got just a few months extra survival (and a lot of pain relief!) from it. It took much longer to get the results for mHSPC men which proved 1 ½ years of extra survival.
I agree that the reduction in NCI funding is very frustrating.
My 'one man trial' of xtandi followed by adding Pluvicto has worked for me - with MedOnc approval, stopped Xtandi and Orgovyx 4 months after final Pluvicto dose. We were testing how effective the Pluvicto was, with the agreement that we would do another PSMA-PET scan after PSA went above 1.00. 15 months later, with no ADT, PSA has very slowly risen, only hit 0.11. In my previous long remission, PSA had hovered between 0.30 to 0.50 (still have my prostate).
Seems to be working for me so far, still playing 'kick the can down the road'!
Hi Allen...thanks for posting this. Currently on Taxotere treatments for the next few months, and then likely Pluvicto after that. You linked a study that showed the benefits of Pluvicto + Xtandi. Since my PSA was doubling rapidly while using Xtandi until a few weeks ago, would reintroducing Xtandi when I get Pluvicto make any sense? Any study on that?
Good question! Unfortunately, I doubt that would help right now. Xtandi only briefly increases the expression of PSMA. After a while, it reduces PSMA expression. However, simultaneous Taxotere can overcome resistance to Xtandi, as in the PRESIDE trial. This is something you may want to discuss with your oncologist.
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ARPI Effect on PSMA Expression/Sensitivity
Would like Opinions about Continuing on Pluvicto Trial
VISION Trial Results Being Released
