Melanoma doctor's high-stakes gamble to treat his brain cancer
bbc.com
bbc.com
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... and 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. 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-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-ii....
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).
Not quite what GP is describing, but it illustrates the point.
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!
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.
Yours is a really balanced take on why maybe it's not so good to have a "wild west" approach to this.
I've gone to two funerals in the past month for friends who lost battles to cancer. I can only hope we're getting closer to radically better treatments.
The most difficult thing is accepting that you cannot control the universe and you can only make the decisions that you can make at the time. With what we do professionally, sometimes we think we have power that we don’t.
My wife was blessed with being treated by an incredible team of doctors at one of the finest cancer centers in the world. They expected full recovery and were shocked when things took a turn. These things are really complex. With advances in scientific computing, genetic analysis is getting faster and better and treatments are improving.
Thats a double edged sword. “OK” in the world of a cancer patient is a relative concept. My experience with the sadness and struggle is that I will remember that these decisions are difficult, and hope is a concept can be both liberating and cruel.
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 :(
https://www.fda.gov/patients/learn-about-expanded-access-and...
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.
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.
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.
Also in ALS, there were major manipulations on social media by companies that claimed their drug was able to cure people, and to prove it they showed on social media well-known patients going to the gym and others doing motocross!
Yet these drugs never shown any benefits in phase III clinical trials...
Even if the FDA is this incredibly competent organization with no corruption, people should have a right to try to live. It's the most dystopian form of the nanny state mentality, IMO.
ALS is devastating, I'm sorry for you and the person you are close to.
Maybe your gripes make more sense in a socialized medicine country. Sure, they have to sacrifice people at the edges. But in the US, there's no excuse. It's like the worst of both private and public medicine.
In terms of benefitting the collective, allowing experimentation on willing subjects with terminal illnesses could really improve medicine, too. It's really just a lose-lose-lose with the current approach. Well, some people win, who manufacture the types of drugs that don't fully cure you but keep you dependent on the prescription until you die. If you don't think that's a factor in the FDA's decisions I have a bridge to sell you.
That's a big claim. Presumably you have big evidence to back it up?
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.
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...
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).
2) Trials are already obscenely (and increasingly) difficult to design and execute even for pure scientific ends. It’s really not trivial to add other objectives like this, even if money were totally irrelevant.
2) And thus the humanitarian part of the trial can serve dual purpose as a training exercise for the additional physicians working with the humanitarian cohort.
Depending on the rarity of the illness, this may be something that the government can easily force pharma companies to accept. They accept far more in regulatory burden and still do business.
Additionally, the pharma company wouldn't allow this because in addition to the upfront design complexity, it would put the trial itself at risk. You're not really allowed to say, "just try it in a bunch of people, it's okay if untrained folks mess it up because if they do we can just throw out the data."
Not opposed to that, but it's not a study cohort. It's just "give investigational drug away for free."
This part:
> You're not really allowed to say, "just try it in a bunch of people, it's okay if untrained folks mess it up because if they do we can just throw out the data."
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> It's just "give investigational drug away for free."
And here insurance regulation can also come in to play along with the pharma regulation.
Sure, none of this would be easy. But the status quo has issues too.
I'm grateful for the work of the doctors in the article, and very hopeful that the treatment works. A close friend of mine was on a trial vaccine for his cancer, which looked promising for a while, but suddenly stopped working - the cancer was ultimately fatal.
I think trials should be offered as potential first steps, especially for aggressive cancers. Patients know the risks. They're either 100% going to die within 6 months to cancer, or, worst case, die trying to fight it, or best case, be cured.
We need really good science and statistics, far superior to p-values, to allow this potentially life saving treatment without the inevitable deaths from people at the limits returning a "not significant" finding for something that actually works.
Maybe something like allowing people who are too far gone to qualify for treatment as part of a study to instead qualify for the experimental treatment with their results only being included as a special "humanitarian" cohort.
I'd also like studies to be able to compare a treatment group against prior control groups, so that everyone today can get the experimental treatment instead of some of them being given a placebo (if there's a lack of another decent treatment to use as a control). If there's nothing effective that can be done as a control, every one should get the treatment.
But the part of me that witnessed glioblastoma - I think when someone is facing that, it should be a VIP pass straight to the "whatever has even a remote chance of actually working" lobby. Which is basically what the article describes, so I'm optimistic for the doctor and his team.
Of course, not everyone is as risk tolerant as I am. My dad wanted to believe he'd be one of the rare "survivors" (I don't think it happens) using traditional radiation and chemo, and was still weighing pros and cons of other potential treatments. But I have the benefit of hindsight, and a lot more education now, and I think it's unethical to not immediately consider trial programs. The most common way to treat glioblastoma today (targeted radiation and chemo) one that only promises to give you more months of life, not years, is also the only treatment option covered by Medicare, the health insurance provider for most retirees in the United States. The uber-aggressive glioblastoma that my dad developed is what most people over retirement age get when they develop glioblastoma as well. Average lifespan from diagnosis to death: 6 months. That's if you surgically remove the tumors, a procedure not without its own risks. Risks that are usually worth it, since without surgically removing the tumors, lifespan drops to weeks.
What I'm saying is there's no path to trial programs for most of the people who'd benefit from those trials the most. It's not even on the map for them.