6 ms·

Melanoma doctor's high-stakes gamble to treat his brain cancer

66 points by rmason 3y ago

jseliger 3y ago
Desperate, Prof Long formulated a radical plan to treat Prof Scolyer based on what had worked in melanoma, but which had never been tested in brain cancer. I don't know how Aus works, but, in the U.S., we need a much more serious right-to-try regime, particularly for fatal diseases like GBM. The FDA is way too slow and paternalistic, a topic that I've been writing about: https://jakeseliger.com/2024/01/29/the-dead-and-dying-at-the-gates-of-oncology-clinical-trials/ https://jakeseliger.com/2024/01/29/the-dead-and-dying-at-the... and https://jakeseliger.com/2023/07/22/i-am-dying-of-squamous-cell-carcinoma-and-the-treatments-that-might-save-me-are-just-out-of-reach/ https://jakeseliger.com/2023/07/22/i-am-dying-of-squamous-ce... because I'm dying from a squamous cell carcinoma infestation that, it turns out, should be much more treatable than it has been so far. For example, MCLA-158 / petosemtamab should, based on existing phase 1a and 1b data, be approved: https://beta.clinicaltrials.gov/study/NCT03526835 https://beta.clinicaltrials.gov/study/NCT03526835. But, from what I understand, the FDA is going to make Merus proceed with phase 3 trials, despite the incredibly positive phase 1b and 2 data. Madness. The FDA killed during the pandemic: https://moreisdifferent.blog/p/fda-devastation-during-the-pandemic https://moreisdifferent.blog/p/fda-devastation-during-the-pa... and continues to kill today. And they worried the experiment could kill him faster. It's a reasonable trade-off to decide to take the risk. Immunotherapy drugs are quite toxic, especially when mixed, so he could be poisoned I wonder which the author is talking about, because e.g. pembrolizumab (Keytruda) is not. I assume the author isn't talking about e.g. CAR-T therapies? If you're in the US and know someone with GBM, look into DCVax: https://www.uclahealth.org/departments/neurosurgery/phase-iii-clinical-trial-evaluating-dcvaxae-l-autologous https://www.uclahealth.org/departments/neurosurgery/phase-ii....
- rswerve 3y ago
  Good luck to you.
- anonymouskimmer 3y ago
  > The FDA killed during the pandemic: https://moreisdifferent.blog/p/fda-devastation-during-the-pa https://moreisdifferent.blog/p/fda-devastation-during-the-pa... and continues to kill today. There are potential trade-offs where experimental treatments which fail preclude other experimental treatments that work. Ethically this is a minefield. Personally I agree that if I have a disease I'd want to take any experimental treatment that seemed like a good idea. I think people's action during the pandemic are a bit more responsible for additional deaths than were FDA delays. : Rapid tests are actually quite sensitive during days ~2-4 of illness when patients are most infectious. Was this known beforehand, or only discovered post-hoc? From your blog: > Regarding drugs, particularly drugs for people who are already effectively dead, like me, we should be moving closer to a surgical model. This seems like a good idea. Though there have been some really bad surgical interventions (lobotomy, sex assignment surgery for intersex conditions or botched circumcisions).
- agumonkey 3y ago
  IIRC former NCI head, Vince de Vita, mentions that early oncology research was pretty much right-to-try by default because they had no data on anything. And it made some people live longer because they could change strategy after the first one failed. Nowadays you have a standard care and if it fails the system will almost drop you out..
  - hiddencost 3y ago
    My grand father was a hematologist and he definitely just tried pet theories on terminal patients
    - JPLeRouzic 3y ago
      Isn't this both unethical and illegal?
      - austinjp 3y ago
        Maybe now, but it hasn't always been so. Attitudes change. If you're lucky enough to chat with someone in their 90s about dying, you may hear stories of how doctors used to "help people on their way". In other words, casual euthanasia was quietly accepted and expected. Not quite what GP is describing, but it illustrates the point.
        toomuchtodo 3y ago
        My mother, long since passed, was a registered nurse (and also carrying far more empathy than most human). She explained morphine pushes and “slow codes” (taking your time so people who wanted to die could) to me in my teens (early to mid 90s). Good terms of art to know when end of life creeps up on you.
- mcbain 3y ago
  I'm not sure if they've said publicly what immunotherapy they used. I have seen it referred to as a combo, so I would guess ipi/nivo - that is Nivolumab (Opdivo) + Ipilimumab (Yervoy). They've been trialling those as neoadjuvant for melanoma: https://melanoma.org.au/paper/neo-adjuvant-immunotherapy-emerges-as-best-medical-practice-and-will-be-the-new-standard-of-care-for-macroscopic-stage-iii-melanoma/ https://melanoma.org.au/paper/neo-adjuvant-immunotherapy-eme... Nivo is generally well tolerated, ipi less so. I only got to my 2nd cycle of ipi/nivo before we discontinued it. (I'd already had more cycles of nivo on a trial.) It can have neurological effects and encephalitis in rare cases, so maybe that's what they are referring to. I wouldn't say "poison" though. As it happens, Prof Long is my medonc. We don't sit around chatting about Richard though, she's a bit busy on clinic days!
  - mcbain 3y ago
    If it doesn't come out beforehand it'll likely be presented at ASCO: https://x.com/profglongmia/status/1753650640847597930 https://x.com/profglongmia/status/1753650640847597930
  - Spooky23 3y ago
    My wife recently fought and unfortunately lost a battle with metastatic melanoma. I would agree that the nivo/ipi combo isn’t poison, but it’s no joke, and given that disease like melanoma sprouts mets like crazy, and the side effects of the treatment can result in significant side effect to critical organs. I think it’s fine to critique the FDA process, but I also think that a conservative approach to approvals is important, because ultimately bad outcomes will cause the pharmaceutical people to get more conservative internally - imo we’re better with a external entity putting the brakes on. It’s a tough business. I’m uncomfortable with the “fuck it give me the newest whatever” attitude that you find in online forums. I’m an IT exec, my wife was a finance professional in healthcare. It was difficult for us to navigate the decisions and risks. Most people are not well equipped to make risk decisions, and dumping experimental consent and other decisions on people facing death with adequate support is a really vicious thing to do. One thing that Molly felt deeply was that the hope she was able to have about beating the cancer was built on the shoulders of those before her. And folks even 10-15 years ago had no hope at all. We have a duty to honor the sacrifice made and be cognizant of what is real and what is not.
- n3storm 3y ago
  I am sorry about your situation, but existing so many companies and startups scamming and trying to scam people I don't feel it's slow and paternalistic (here in EU is even "slower" than in USA) Perhaps scammers should stop using health for their "getting rich fast" plots so this rules could be relaxed, but that is asking pathological narcisists to think about others which is not going to happen anytime soon :(
- pkaye 3y ago
  What about the "right to try" option in the US? https://www.fda.gov/patients/learn-about-expanded-access-and-other-treatment-options/right-try https://www.fda.gov/patients/learn-about-expanded-access-and...
Mathnerd314 3y ago
I read articles like these, where the treatment is at least somewhat successful, and I wonder how many instances there are where they tried an experimental treatment but the patient died anyway.
- satori99 3y ago
  My step father was diagnosed with metastasized melanoma in 2019, and was completely cured by treatments developed by professors Scolyer and Long. He needed surgery to remove small tumors on his lungs, but the drugs made his melanoma just disappear. He was very lucky. Not only because he was offered to take part in a trial, but also because only a small number of patients had complete success stories like his. The link below is to a very similar case from the same trial: https://7news.com.au/lifestyle/health-wellbeing/miracle-drug-for-melanoma-identified-c-3003352 https://7news.com.au/lifestyle/health-wellbeing/miracle-drug...
- xiphias2 3y ago
  It's standard protocol to take part in cancer trials after cancer stops responding to all approved treatments. Of course this article is different from organized trials.
  - anonymouskimmer 3y ago
    According to jseliger's blog above it takes real work to get yourself into a cancer trial.
    - ethanbond 3y ago
      Trials aren't really designed to be care-giving mechanisms. It's not a goal to be easy to get into. They just need to fill the trials with eligible patients and that's it, obviously very unfortunately for a lot of folks.
      - anonymouskimmer 3y ago
        > Trials aren't really designed to be care-giving mechanisms. Sure, but they could be. Easy enough to gain profit from those who get the disease at a later date. If a current standard of care treatment is used as a control for say, half of the cohort, there could be some way to charge every participant's insurance for half the cost of the standard of care (with the other half getting the experimental treatment on a blinded basis).
pazimzadeh 3y ago
> under the care of Prof Long and a team of experts, Prof Scolyer became the first brain cancer patient to ever have combination, pre-surgery immunotherapy Great, although it's sad that you seemingly have to be a doctor to convince another doctor to try things like this. Now let's extend this concept to giving immunotherapy before chemotherapy, since chemotherapy wipes your immune system. It doesn't make sense to do chemo before immunotherapy when you want the immune system to attack the cancer. On the other hand, if the immune system goes on a rampage against healthy cells, then chemo could be used to wipe it again, while also stopping cancer growth.
duffpkg 3y ago
First, do no harm. This is a foundational tenant that permeates healthcare. As a former health system executive I have been in positition to influence decision making about high risk experimental treatments in certain cases. In the US currently, in most states, you as a patient have a more or less unlimited right to try experimental treatments if you are facing a reasonable likelihood of death otherwise. The FDA plays a very limited role in one-off situations though they are frequently made to play the villain. The reality is that there are legal avenues available much of the time that providers and companies are loathe to employ. Much of the time drug companies and doctors have lots of reasons not to want to roll the dice if they think the odds of success are low enough. The risk/reward is a very different outlook for the patient than the providers and companies that may need to be a party to the treatment. There are reprecussions to all patient deaths as a result of an experimental treatment however well intended and consented. A complicating factor that weighs over everything is that there is a long history of terrible abuse of informed consent with less privileged patients, puerto rico is a trainwreck of abuse going back a century but there are many more. As an administrator I always felt that patients who are freely giving informed consent always have the right to try, however slim the chance of success. But, it can be brutally difficult to parse out those instances where influence, coercion or even misrepresentation are at play with a particular patient and family. Family dynamics of course can play a large role too.
- fzeroracer 3y ago
  Yeah, I agree with this. Ultimately the danger is that right to try essentially leads patients to deny proven methods of treatment due to coercion or being misled. If a patient refuses the usual cancer treatment and demands instead a regime of herbs and folk medicine, how do you handle that? Especially when the family then turns around and blames you. In this scenario where you have an expert in their field knowing that the outcome for the experimental treatment could make things far worse but is willing to contribute the data to further the field anyways I think the answer is far easier to parse.
- lend000 3y ago
  Someone close to me has ALS and their only options seem to be in Mexico and China, not anywhere in the US. From their research, it definitely seems like the FDA is the big bad not only in preventing treatments as a default, but also by disincentivizing companies from allowing dying people to trial unapproved treatments if their condition is far gone enough that there is a low chance of success. My understanding is that this is partially because people who take treatments and die (even if they were going to die no matter what, and did not die from the treatment itself) are used by the FDA against the biotech companies when seeking approval.

66 points by rmason 3y ago

Desperate, Prof Long formulated a radical plan to treat Prof Scolyer based on what had worked in melanoma, but which had never been tested in brain cancer. I don't know how Aus works, but, in the U.S., we need a much more serious right-to-try regime, particularly for fatal diseases like GBM. The FDA is way too slow and paternalistic, a topic that I've been writing about: https://jakeseliger.com/2024/01/29/the-dead-and-dying-at-the-gates-of-oncology-clinical-trials/ https://jakeseliger.com/2024/01/29/the-dead-and-dying-at-the... and https://jakeseliger.com/2023/07/22/i-am-dying-of-squamous-cell-carcinoma-and-the-treatments-that-might-save-me-are-just-out-of-reach/ https://jakeseliger.com/2023/07/22/i-am-dying-of-squamous-ce... because I'm dying from a squamous cell carcinoma infestation that, it turns out, should be much more treatable than it has been so far. For example, MCLA-158 / petosemtamab should, based on existing phase 1a and 1b data, be approved: https://beta.clinicaltrials.gov/study/NCT03526835 https://beta.clinicaltrials.gov/study/NCT03526835. But, from what I understand, the FDA is going to make Merus proceed with phase 3 trials, despite the incredibly positive phase 1b and 2 data. Madness. The FDA killed during the pandemic: https://moreisdifferent.blog/p/fda-devastation-during-the-pandemic https://moreisdifferent.blog/p/fda-devastation-during-the-pa... and continues to kill today. And they worried the experiment could kill him faster. It's a reasonable trade-off to decide to take the risk. Immunotherapy drugs are quite toxic, especially when mixed, so he could be poisoned I wonder which the author is talking about, because e.g. pembrolizumab (Keytruda) is not. I assume the author isn't talking about e.g. CAR-T therapies? If you're in the US and know someone with GBM, look into DCVax: https://www.uclahealth.org/departments/neurosurgery/phase-iii-clinical-trial-evaluating-dcvaxae-l-autologous https://www.uclahealth.org/departments/neurosurgery/phase-ii....

rswerve 3y ago
Good luck to you.
anonymouskimmer 3y ago
> The FDA killed during the pandemic: https://moreisdifferent.blog/p/fda-devastation-during-the-pa https://moreisdifferent.blog/p/fda-devastation-during-the-pa... and continues to kill today. There are potential trade-offs where experimental treatments which fail preclude other experimental treatments that work. Ethically this is a minefield. Personally I agree that if I have a disease I'd want to take any experimental treatment that seemed like a good idea. I think people's action during the pandemic are a bit more responsible for additional deaths than were FDA delays. : Rapid tests are actually quite sensitive during days ~2-4 of illness when patients are most infectious. Was this known beforehand, or only discovered post-hoc? From your blog: > Regarding drugs, particularly drugs for people who are already effectively dead, like me, we should be moving closer to a surgical model. This seems like a good idea. Though there have been some really bad surgical interventions (lobotomy, sex assignment surgery for intersex conditions or botched circumcisions).
agumonkey 3y ago
IIRC former NCI head, Vince de Vita, mentions that early oncology research was pretty much right-to-try by default because they had no data on anything. And it made some people live longer because they could change strategy after the first one failed. Nowadays you have a standard care and if it fails the system will almost drop you out..
- hiddencost 3y ago
  My grand father was a hematologist and he definitely just tried pet theories on terminal patients
  - JPLeRouzic 3y ago
    Isn't this both unethical and illegal?
    - austinjp 3y ago
      Maybe now, but it hasn't always been so. Attitudes change. If you're lucky enough to chat with someone in their 90s about dying, you may hear stories of how doctors used to "help people on their way". In other words, casual euthanasia was quietly accepted and expected. Not quite what GP is describing, but it illustrates the point.
      - toomuchtodo 3y ago
        My mother, long since passed, was a registered nurse (and also carrying far more empathy than most human). She explained morphine pushes and “slow codes” (taking your time so people who wanted to die could) to me in my teens (early to mid 90s). Good terms of art to know when end of life creeps up on you.
mcbain 3y ago
I'm not sure if they've said publicly what immunotherapy they used. I have seen it referred to as a combo, so I would guess ipi/nivo - that is Nivolumab (Opdivo) + Ipilimumab (Yervoy). They've been trialling those as neoadjuvant for melanoma: https://melanoma.org.au/paper/neo-adjuvant-immunotherapy-emerges-as-best-medical-practice-and-will-be-the-new-standard-of-care-for-macroscopic-stage-iii-melanoma/ https://melanoma.org.au/paper/neo-adjuvant-immunotherapy-eme... Nivo is generally well tolerated, ipi less so. I only got to my 2nd cycle of ipi/nivo before we discontinued it. (I'd already had more cycles of nivo on a trial.) It can have neurological effects and encephalitis in rare cases, so maybe that's what they are referring to. I wouldn't say "poison" though. As it happens, Prof Long is my medonc. We don't sit around chatting about Richard though, she's a bit busy on clinic days!
- mcbain 3y ago
  If it doesn't come out beforehand it'll likely be presented at ASCO: https://x.com/profglongmia/status/1753650640847597930 https://x.com/profglongmia/status/1753650640847597930
- Spooky23 3y ago
  My wife recently fought and unfortunately lost a battle with metastatic melanoma. I would agree that the nivo/ipi combo isn’t poison, but it’s no joke, and given that disease like melanoma sprouts mets like crazy, and the side effects of the treatment can result in significant side effect to critical organs. I think it’s fine to critique the FDA process, but I also think that a conservative approach to approvals is important, because ultimately bad outcomes will cause the pharmaceutical people to get more conservative internally - imo we’re better with a external entity putting the brakes on. It’s a tough business. I’m uncomfortable with the “fuck it give me the newest whatever” attitude that you find in online forums. I’m an IT exec, my wife was a finance professional in healthcare. It was difficult for us to navigate the decisions and risks. Most people are not well equipped to make risk decisions, and dumping experimental consent and other decisions on people facing death with adequate support is a really vicious thing to do. One thing that Molly felt deeply was that the hope she was able to have about beating the cancer was built on the shoulders of those before her. And folks even 10-15 years ago had no hope at all. We have a duty to honor the sacrifice made and be cognizant of what is real and what is not.
n3storm 3y ago
I am sorry about your situation, but existing so many companies and startups scamming and trying to scam people I don't feel it's slow and paternalistic (here in EU is even "slower" than in USA) Perhaps scammers should stop using health for their "getting rich fast" plots so this rules could be relaxed, but that is asking pathological narcisists to think about others which is not going to happen anytime soon :(
pkaye 3y ago
What about the "right to try" option in the US? https://www.fda.gov/patients/learn-about-expanded-access-and-other-treatment-options/right-try https://www.fda.gov/patients/learn-about-expanded-access-and...

Mathnerd314 3y ago

I read articles like these, where the treatment is at least somewhat successful, and I wonder how many instances there are where they tried an experimental treatment but the patient died anyway.

satori99 3y ago
My step father was diagnosed with metastasized melanoma in 2019, and was completely cured by treatments developed by professors Scolyer and Long. He needed surgery to remove small tumors on his lungs, but the drugs made his melanoma just disappear. He was very lucky. Not only because he was offered to take part in a trial, but also because only a small number of patients had complete success stories like his. The link below is to a very similar case from the same trial: https://7news.com.au/lifestyle/health-wellbeing/miracle-drug-for-melanoma-identified-c-3003352 https://7news.com.au/lifestyle/health-wellbeing/miracle-drug...
xiphias2 3y ago
It's standard protocol to take part in cancer trials after cancer stops responding to all approved treatments. Of course this article is different from organized trials.
- anonymouskimmer 3y ago
  According to jseliger's blog above it takes real work to get yourself into a cancer trial.
  - ethanbond 3y ago
    Trials aren't really designed to be care-giving mechanisms. It's not a goal to be easy to get into. They just need to fill the trials with eligible patients and that's it, obviously very unfortunately for a lot of folks.
    - anonymouskimmer 3y ago
      > Trials aren't really designed to be care-giving mechanisms. Sure, but they could be. Easy enough to gain profit from those who get the disease at a later date. If a current standard of care treatment is used as a control for say, half of the cohort, there could be some way to charge every participant's insurance for half the cost of the standard of care (with the other half getting the experimental treatment on a blinded basis).

pazimzadeh 3y ago

> under the care of Prof Long and a team of experts, Prof Scolyer became the first brain cancer patient to ever have combination, pre-surgery immunotherapy Great, although it's sad that you seemingly have to be a doctor to convince another doctor to try things like this. Now let's extend this concept to giving immunotherapy before chemotherapy, since chemotherapy wipes your immune system. It doesn't make sense to do chemo before immunotherapy when you want the immune system to attack the cancer. On the other hand, if the immune system goes on a rampage against healthy cells, then chemo could be used to wipe it again, while also stopping cancer growth.

duffpkg 3y ago

First, do no harm. This is a foundational tenant that permeates healthcare. As a former health system executive I have been in positition to influence decision making about high risk experimental treatments in certain cases. In the US currently, in most states, you as a patient have a more or less unlimited right to try experimental treatments if you are facing a reasonable likelihood of death otherwise. The FDA plays a very limited role in one-off situations though they are frequently made to play the villain. The reality is that there are legal avenues available much of the time that providers and companies are loathe to employ. Much of the time drug companies and doctors have lots of reasons not to want to roll the dice if they think the odds of success are low enough. The risk/reward is a very different outlook for the patient than the providers and companies that may need to be a party to the treatment. There are reprecussions to all patient deaths as a result of an experimental treatment however well intended and consented. A complicating factor that weighs over everything is that there is a long history of terrible abuse of informed consent with less privileged patients, puerto rico is a trainwreck of abuse going back a century but there are many more. As an administrator I always felt that patients who are freely giving informed consent always have the right to try, however slim the chance of success. But, it can be brutally difficult to parse out those instances where influence, coercion or even misrepresentation are at play with a particular patient and family. Family dynamics of course can play a large role too.

fzeroracer 3y ago
Yeah, I agree with this. Ultimately the danger is that right to try essentially leads patients to deny proven methods of treatment due to coercion or being misled. If a patient refuses the usual cancer treatment and demands instead a regime of herbs and folk medicine, how do you handle that? Especially when the family then turns around and blames you. In this scenario where you have an expert in their field knowing that the outcome for the experimental treatment could make things far worse but is willing to contribute the data to further the field anyways I think the answer is far easier to parse.
lend000 3y ago
Someone close to me has ALS and their only options seem to be in Mexico and China, not anywhere in the US. From their research, it definitely seems like the FDA is the big bad not only in preventing treatments as a default, but also by disincentivizing companies from allowing dying people to trial unapproved treatments if their condition is far gone enough that there is a low chance of success. My understanding is that this is partially because people who take treatments and die (even if they were going to die no matter what, and did not die from the treatment itself) are used by the FDA against the biotech companies when seeking approval.