Thank you for highlighting this. As a former marketer and now a visual storyteller working with my wife, who was diagnosed with cancer seven years ago, this resonates deeply. We've often encountered inauthentic representations of illness—either overly tragic or unrealistically triumphant—leaving little space for the complex emotional middle ground that many people experience.
While there’s some research on how words impact the patient and caregiver community, I’ve seen little about how visual depictions affect mental health. If you know of any, I’d love to hear about it. From our work over the past seven years, it’s clear many people feel unseen, their experiences misrepresented or sugar-coated, often for profit, which only deepens feelings of isolation.
In our own work, including our recently released photobook HER2: The Diagnosed, The Caregiver, and Their Son, we’ve aimed to share more nuanced stories.
Dr. Holden may not be aware that a drug he may have used as an advanced prostate cancer patient, abiraterone acetate (Zytiga), was FDA approved in 2011 based on improved overall survival of 3.9 months (LATITUDE trial). Today abi is widely considered to be the preferred 2nd line drug on recurrence or metastasis.
Patients in many oncology clinical trials are seriously advanced. This was the case for the VISION trial that led to Pluvicto's approval. AnCan supported several. Criticizing a trial OS frequen tly lacks basis and reveals poor understanding. Trial OS is a median; many patients survive much longer in reality, especially those less advanced. Medical professionals should be wise to this. And if Dr. Holden has used abi himself, I'd bet he thinks 3.9 months is clinically significant.
One other point - 43% of men with the level of disease for which Pluvicto is approved do not even receive a 2nd line of treatment, according to research published in JAMA Network last month https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2827616?mc_cid=64e0c6d12c&mc_eid=838454d636. Any advertisement that drives advanced prostate cancer men to discuss additional treatment with their providers may arguably be a public service.
Hi Richard. You don't know me, though you made some assumptions about me, which are wrong, by the way. I find it strange you'd lecture me on median overall survival. Median OS of four months means that at the four-month time point, a whopping 50% of the patients treated with Pluvicto had died.
Since you want to discuss clinical trials, we can discuss how poorly designed the VISION trial was, which resulted in Pluvicto's FDA approval. The trial’s control arm allowed suboptimal treatment, limiting the use of pharmaceuticals with a survival benefit.
This was a disservice to the men in the control arm, who might otherwise have received the real standard of care outside this clinical trial. Some might say it was malpractice.
For example, 50% of men in the control arm were eligible for cabazitaxel, which showed a survival benefit over ARPIs in the CARD trial. But they couldn’t get it because of the VISION trial rules.
Nor could men in the control arm with only bone mets get systemic radioisotopes like radium-223, which has shown a median OS of 15 months!
In addition, 55% of men in the control group had already received one ARPI, and 39% had already received two. This significantly limits hormone therapy options in the control group because the clinical efficacy of an ARPI switch is terrible.
A control group should always get drugs that are the prevailing standard of care, and in the VISION trial, men in the control group were deprived of the prevailing standard of care. That is not ethical.
In addition, this phenomenon of a suboptimal control arm is popular with pharma-sponsored clinical trials. Why? Because poorly designed control arms that don’t allow life-prolonging therapies potentially make the study (drug) look better than it is.
The VISION trial designers’ rationale for excluding certain treatments was that the safety profile of these therapies had not been established with Lu-PSMA-617. However, that is no excuse for creating a terrible control arm. They could have allowed men in the control arm to receive cabazitaxel.
If I were a man enrolled in a clinical trial that prevented me from taking the prevailing standard of care therapy that has the potential to prolong my life, I would be angry and drop out of the study. And that appears to be what happened in the VISION trial.
After the trial started, the control group had an extremely high incidence of withdrawal—56%—which was mainly attributed to patient disappointment. This example of extreme control arm censoring skews trial results, making downstream endpoints more unreliable.
When the trial designers saw this, they implemented trial-site education measures to reduce the incidence of withdrawal—basically, they convinced patients to stay in a lousy control arm. That's just wrong.
Advertisement that drives prostate cancer patients to discuss treatments founded on poorly designed clinical trials is not a public service. Pharmaceutical companies and clinical trial investigators need to do better for men with prostate cancer.
Good comment, doc. I know and have discussed options with two gentlemen who have advanced PCa who traveled to Australia and India respectively to obtain radioligand infusions and paid for the treatments themselves. They went early in their PCa treatment program prior to SOC hormone therapy or chemo, and both are still alive several years later. Both were physicians having retired following their PCa diagnosis. Some gents travel to Germany, Israel and Great Britain for thé infusions. Drug RCT for men in later stages of cancer progression use subjects with totally fragile and worn out bodies instead of using subjects who are stronger and healthier in the early stages of their diseases. That is a nasty uncaring protocol.
Hi, Mr. Dwyer. I think you are spot on with this observation. Most American men with prostate cancer don't know that while the PSMA protein was discovered in the U.S., German physicians, specifically Dr. Richard Baum, took that information and ran with it, developing PSMA radioligand therapy (RLT). The U.S. version of PSMA RLT is Pluvicto.
When phase 3 clinical trials for PSMA RLT started in the U.S., Germany was about ten years ahead of the U.S., and Australia was about five years ahead of the U.S. in treating/studying men with it. Australia got on board early because Dr. Michael Hofman traveled to Germany and did a sabbatical under Dr. Baum.
Dr. Hofman leads the Prostate Cancer Theranostics and Imaging Centre of Excellence (ProsTIC) at Melbourne's Peter MacCallum Cancer Centre. He has been the Principal Investigator on many groundbreaking PSMA RLT studies in that country.
Dr. Baum has been successfully treating men with prostate cancer from all over the world, including many Americans, before the VISION trial even began enrolling patients. And many of those men were treated earlier in their disease than the American regulations allow. He found that some men do much better with PSMA RLT earlier in their disease. It makes total sense - their bodies haven't been ravaged by disease and chemotherapy.
American and Australian doctors and researchers think Dr. Baum is a rogue doctor because he successfully uses PSMA RLT in individuals without those men being in a study and also because he has successfully treated men with prostate cancer in earlier stages than American and Australian regulations allow.
American and Australian doctors are now studying PSMA RLT in the earlier stages of the disease, but only under strict clinical trial regulations. Meanwhile, most men who can't tolerate ADT/ARPIs and who might respond to PSMA RLT (high SUV with concordant PET scans) can't get Pluvicto here, even in clinical trials.
If I had metastatic hormone-sensitive disease, couldn't take ADT/ARPIs (I can't tolerate them), had high SUV scores on PSMA PET scans, and had concordant PET scans (PSMA + FDG), I'd be first in line to consult with doctors like Baum who offers PSMA RLT "off label."
One of the reasons why the mOS of Pluvicto was only 4 months in the VISION trial is because these men were really sick and ravaged by disease and chemotherapy.
The oncology research wheel works based on "unmet need," considering limited treatment options for patients with advanced disease. Because of the risk-benefit assessment, researchers also study oncology therapies in advanced disease. Advanced cancer patients also typically have obvious measurable disease progression, allowing researchers to determine if a treatment works more quickly.
While these are all good ideals, sometimes, as in the case of PSMA RLT, there is enough evidence from 15 years of use in other countries to show that you don't need to completely reinvent the wheel. Americans could have started some trials with men much earlier in their disease process, long before now.
Please clarify what assumptions you suggest I made about you. My only personal remark, Dr. Holden, is to ask if you were on abi? Were You? I assumed zippo about you.
You are absolutely right about the control arm, but that is not what we're discussing, Dr Holden. A properly designed control arm may have yielded an even shorter OS difference. I'm happy to get into the details of the VISION trial, and we will most likely agree. If you'd like to debate trial design with Sartor, Morris et al, maybe we can facilitate.
Btw, if you really want to discuss trial design, the greatest flaw IMHO was not in the design of the control protocol. The VISION trial failed to include concordant FDG scans as a condition of entry, as Michael Hofman does in his trials Down Under. At the outset the trial was biased for a short OS because it was not excluding men predestined to fail. For me that's a lot more significant than no chemo in the control. A taxane based chemo alone would not have helped men who were failing because of significant loads of non-PSMA expressing cancer.
Sadly you failed to acknowledge my key point while wandering around other deficiencies of the VISION trial on which we may well agree.
My take home point in objecting to your criticism of the clinical value of Pluvicto is that many drugs treating advanced cancers, and certainly advanced prostate cancer, admit patients into the trial at a very late stage.
Sadly, trials are designed to achieve drug approvals rather than to provide benchmarks on which clinicians should base decisions.
@JPDwyer confirms what I am saying in his comment.
In your expansive response to @JPDwyer you make the very point Imade to you above. You say,
"One of the reasons why the mOS of Pluvicto was only 4 months in the VISION trial is because these men were really sick and ravaged by disease and chemotherapy."
EXACTLY... so how in the same breath can you be critical of 4 months as not clinically significant.
I think you may have just hoisted yourself by your own petard.
This ad reminds me of the AARP scam advertising about all the sports and golf cart driving that geezers enjoy at Disney or UnitedHealthcare owned timeshare retirement communities. Just horse dung dressed up as a hope again our inevitable aging process. J. P. Dwyer
Thank you for highlighting this. As a former marketer and now a visual storyteller working with my wife, who was diagnosed with cancer seven years ago, this resonates deeply. We've often encountered inauthentic representations of illness—either overly tragic or unrealistically triumphant—leaving little space for the complex emotional middle ground that many people experience.
While there’s some research on how words impact the patient and caregiver community, I’ve seen little about how visual depictions affect mental health. If you know of any, I’d love to hear about it. From our work over the past seven years, it’s clear many people feel unseen, their experiences misrepresented or sugar-coated, often for profit, which only deepens feelings of isolation.
In our own work, including our recently released photobook HER2: The Diagnosed, The Caregiver, and Their Son, we’ve aimed to share more nuanced stories.
I often wonder if these ads should be labeled direct to investors as opposed to direct to consumers.
Dr. Holden may not be aware that a drug he may have used as an advanced prostate cancer patient, abiraterone acetate (Zytiga), was FDA approved in 2011 based on improved overall survival of 3.9 months (LATITUDE trial). Today abi is widely considered to be the preferred 2nd line drug on recurrence or metastasis.
Patients in many oncology clinical trials are seriously advanced. This was the case for the VISION trial that led to Pluvicto's approval. AnCan supported several. Criticizing a trial OS frequen tly lacks basis and reveals poor understanding. Trial OS is a median; many patients survive much longer in reality, especially those less advanced. Medical professionals should be wise to this. And if Dr. Holden has used abi himself, I'd bet he thinks 3.9 months is clinically significant.
One other point - 43% of men with the level of disease for which Pluvicto is approved do not even receive a 2nd line of treatment, according to research published in JAMA Network last month https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2827616?mc_cid=64e0c6d12c&mc_eid=838454d636. Any advertisement that drives advanced prostate cancer men to discuss additional treatment with their providers may arguably be a public service.
Hi Richard. You don't know me, though you made some assumptions about me, which are wrong, by the way. I find it strange you'd lecture me on median overall survival. Median OS of four months means that at the four-month time point, a whopping 50% of the patients treated with Pluvicto had died.
Since you want to discuss clinical trials, we can discuss how poorly designed the VISION trial was, which resulted in Pluvicto's FDA approval. The trial’s control arm allowed suboptimal treatment, limiting the use of pharmaceuticals with a survival benefit.
This was a disservice to the men in the control arm, who might otherwise have received the real standard of care outside this clinical trial. Some might say it was malpractice.
For example, 50% of men in the control arm were eligible for cabazitaxel, which showed a survival benefit over ARPIs in the CARD trial. But they couldn’t get it because of the VISION trial rules.
Nor could men in the control arm with only bone mets get systemic radioisotopes like radium-223, which has shown a median OS of 15 months!
In addition, 55% of men in the control group had already received one ARPI, and 39% had already received two. This significantly limits hormone therapy options in the control group because the clinical efficacy of an ARPI switch is terrible.
A control group should always get drugs that are the prevailing standard of care, and in the VISION trial, men in the control group were deprived of the prevailing standard of care. That is not ethical.
In addition, this phenomenon of a suboptimal control arm is popular with pharma-sponsored clinical trials. Why? Because poorly designed control arms that don’t allow life-prolonging therapies potentially make the study (drug) look better than it is.
The VISION trial designers’ rationale for excluding certain treatments was that the safety profile of these therapies had not been established with Lu-PSMA-617. However, that is no excuse for creating a terrible control arm. They could have allowed men in the control arm to receive cabazitaxel.
If I were a man enrolled in a clinical trial that prevented me from taking the prevailing standard of care therapy that has the potential to prolong my life, I would be angry and drop out of the study. And that appears to be what happened in the VISION trial.
After the trial started, the control group had an extremely high incidence of withdrawal—56%—which was mainly attributed to patient disappointment. This example of extreme control arm censoring skews trial results, making downstream endpoints more unreliable.
When the trial designers saw this, they implemented trial-site education measures to reduce the incidence of withdrawal—basically, they convinced patients to stay in a lousy control arm. That's just wrong.
Advertisement that drives prostate cancer patients to discuss treatments founded on poorly designed clinical trials is not a public service. Pharmaceutical companies and clinical trial investigators need to do better for men with prostate cancer.
Good comment, doc. I know and have discussed options with two gentlemen who have advanced PCa who traveled to Australia and India respectively to obtain radioligand infusions and paid for the treatments themselves. They went early in their PCa treatment program prior to SOC hormone therapy or chemo, and both are still alive several years later. Both were physicians having retired following their PCa diagnosis. Some gents travel to Germany, Israel and Great Britain for thé infusions. Drug RCT for men in later stages of cancer progression use subjects with totally fragile and worn out bodies instead of using subjects who are stronger and healthier in the early stages of their diseases. That is a nasty uncaring protocol.
Hi, Mr. Dwyer. I think you are spot on with this observation. Most American men with prostate cancer don't know that while the PSMA protein was discovered in the U.S., German physicians, specifically Dr. Richard Baum, took that information and ran with it, developing PSMA radioligand therapy (RLT). The U.S. version of PSMA RLT is Pluvicto.
When phase 3 clinical trials for PSMA RLT started in the U.S., Germany was about ten years ahead of the U.S., and Australia was about five years ahead of the U.S. in treating/studying men with it. Australia got on board early because Dr. Michael Hofman traveled to Germany and did a sabbatical under Dr. Baum.
Dr. Hofman leads the Prostate Cancer Theranostics and Imaging Centre of Excellence (ProsTIC) at Melbourne's Peter MacCallum Cancer Centre. He has been the Principal Investigator on many groundbreaking PSMA RLT studies in that country.
Dr. Baum has been successfully treating men with prostate cancer from all over the world, including many Americans, before the VISION trial even began enrolling patients. And many of those men were treated earlier in their disease than the American regulations allow. He found that some men do much better with PSMA RLT earlier in their disease. It makes total sense - their bodies haven't been ravaged by disease and chemotherapy.
American and Australian doctors and researchers think Dr. Baum is a rogue doctor because he successfully uses PSMA RLT in individuals without those men being in a study and also because he has successfully treated men with prostate cancer in earlier stages than American and Australian regulations allow.
American and Australian doctors are now studying PSMA RLT in the earlier stages of the disease, but only under strict clinical trial regulations. Meanwhile, most men who can't tolerate ADT/ARPIs and who might respond to PSMA RLT (high SUV with concordant PET scans) can't get Pluvicto here, even in clinical trials.
If I had metastatic hormone-sensitive disease, couldn't take ADT/ARPIs (I can't tolerate them), had high SUV scores on PSMA PET scans, and had concordant PET scans (PSMA + FDG), I'd be first in line to consult with doctors like Baum who offers PSMA RLT "off label."
One of the reasons why the mOS of Pluvicto was only 4 months in the VISION trial is because these men were really sick and ravaged by disease and chemotherapy.
The oncology research wheel works based on "unmet need," considering limited treatment options for patients with advanced disease. Because of the risk-benefit assessment, researchers also study oncology therapies in advanced disease. Advanced cancer patients also typically have obvious measurable disease progression, allowing researchers to determine if a treatment works more quickly.
While these are all good ideals, sometimes, as in the case of PSMA RLT, there is enough evidence from 15 years of use in other countries to show that you don't need to completely reinvent the wheel. Americans could have started some trials with men much earlier in their disease process, long before now.
Thanks for your comment! Keith
Please clarify what assumptions you suggest I made about you. My only personal remark, Dr. Holden, is to ask if you were on abi? Were You? I assumed zippo about you.
You are absolutely right about the control arm, but that is not what we're discussing, Dr Holden. A properly designed control arm may have yielded an even shorter OS difference. I'm happy to get into the details of the VISION trial, and we will most likely agree. If you'd like to debate trial design with Sartor, Morris et al, maybe we can facilitate.
Btw, if you really want to discuss trial design, the greatest flaw IMHO was not in the design of the control protocol. The VISION trial failed to include concordant FDG scans as a condition of entry, as Michael Hofman does in his trials Down Under. At the outset the trial was biased for a short OS because it was not excluding men predestined to fail. For me that's a lot more significant than no chemo in the control. A taxane based chemo alone would not have helped men who were failing because of significant loads of non-PSMA expressing cancer.
Sadly you failed to acknowledge my key point while wandering around other deficiencies of the VISION trial on which we may well agree.
My take home point in objecting to your criticism of the clinical value of Pluvicto is that many drugs treating advanced cancers, and certainly advanced prostate cancer, admit patients into the trial at a very late stage.
Sadly, trials are designed to achieve drug approvals rather than to provide benchmarks on which clinicians should base decisions.
@JPDwyer confirms what I am saying in his comment.
In your expansive response to @JPDwyer you make the very point Imade to you above. You say,
"One of the reasons why the mOS of Pluvicto was only 4 months in the VISION trial is because these men were really sick and ravaged by disease and chemotherapy."
EXACTLY... so how in the same breath can you be critical of 4 months as not clinically significant.
I think you may have just hoisted yourself by your own petard.
Onward & upwards, rick
This ad reminds me of the AARP scam advertising about all the sports and golf cart driving that geezers enjoy at Disney or UnitedHealthcare owned timeshare retirement communities. Just horse dung dressed up as a hope again our inevitable aging process. J. P. Dwyer
Well done, Dr. Holden. Sorry, Mr. Davis, but you sound like a drug rep that drank the kool-aid.
Just breaking out of the conspiracy theories, considering pros and cons, and doing what it takes to get pharma to listen to us patients.