Immunotherapy Is Changing Cancer Treatment Forever
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I don’t mean videos of us together doing stuff (I.e. memories) but videos meant directly for them to watch. I’m thinking about giving them advice for adulthood and telling them about who I am, and also tell them about who they are as kids (so they can remember it after they grow up). But I’m still not convinced it’s a good idea.
That itself is incredibly difficult as most people can't describe who they are beyond their name and title.
Ctrl+f "video"
I wish I had more videos and audio recordings of her. I wish I had handwritten letters from her. I wish I had audio/video of stories and family history only she would know. Above all, I don’t think I would have found any of the above weird or morbid, and I doubt your children (or spouse?) will either. I know my siblings feel the same as I do. You should feel safe in knowing that they will deeply appreciate any artifacts you leave behind for them to think about when they miss you.
I’m sorry for what you’re going through, and I wish you and your family the best.
As you mentioned, the big issues are around infections. It completely wipes out the immune system, including all vaccinations. Every vaccination needs to be taken again, once the body is recovered from the initial therapy.
My Mum recently contracted COVID and is in hospital being given Paxlovid. She had COVID a while ago and it was nothing compared to her current state. CAR-T made it significantly worse but will hopefully be worth it in the long term.
I'm saddened by your news but - given what I've experienced with my Mum during her cancer journey - can understand the difficult decision you've made.
Herceptin (trastuzumab) is mainly for HER-2 overexpression, whereas I have HER-2 mutation. However, we did try it last year alongside another chemo whose name I cannot remember, and IIRC that's the combo which gave me neuropathy in my feet (I now take lots of gabapentin every day so my feet don't feel like they're on fire).
Other than the clinical trial drug, which helped for a few months, the one thing that did help but eventually gave me pneumonitis so I had to stop it, was Enhertu.
Do you follow the work of Dr. Seyfried at Boston University?
I think immunotherapy is great and going to save many lives, but there are still some things that need to be worked out before it's perfect.
Nivo is used a lot for melanoma, also commonly in combo with ipi (ipilimumab, yervoy). Pembro (keytruda) is the other common one.
Anyway, any of these can have adverse effects so patients are closely monitored.
For me, my thyroid didn't like nivo much but recovered. But we stopped after a couple of cycles of ipi+nivo because I was starting to develop colitis. And more importantly it wasn't slowing development of my melanomas.
Nearing the end of life for a family member
There are other targeted therapies depending on the genetic makeup of the tumor.
BRAF, RAS, KRAS, NRAS, HER2, BRCA, …
Maybe start here. There’s an incredible amount to learn.
https://amp.cancer.org/cancer/types/ovarian-cancer/treating/...
One really interesting advance is histotripsy which uses ultrasound to go after the cancer that has spread to your liver.
https://histosonics.com/the-science/
Lots of informative YouTube videos. Look for ones by ASCO, Stanford, Mayo,MD Anderson, …
https://www.cancer.gov/research/participate/clinical-trials-...
https://www.mdanderson.org/cancerwise/ovarian-cancer-survivo...
Another potential protocol involves azenosertib in patients with high-grade serous ovarian, fallopian tube, or primary peritoneal cancer.
https://www.onclive.com/view/dr-westin-on-early-findings-wit...
(not a doctor, not medical advice, just connecting dots, please take citations to a highly competent practitioner in this specific medicine domain such as the oncologist care provider/team of the patient you are advocating for, this is simply due diligence to prevent potential blindspots, we are all just human)
Also, keep in mind that this article, like so many such articles, was probably a paid industry advertisement. I'm assuming by this time, everyone is aware of graham's submarine article.
Maybe it will change cancer treatment forever, but as far as I know, cancer patients still go through some form of surgery, radiation, chemotherapy, etc.
I have no insight into the OP’s case in particular, but this is objectively untrue in a large majority of cases. The percentage of oncologists who stay on top of and recommend clinical trials to their patients is in the single digits. One thing I’ve learned from following Jake Seliger’s excellent blog [0] is that cancer patients are often on their own when it comes to researching and applying to clinical trials.
And, IMO, this mostly makes sense. There's very limited spots and eligibility criteria; we can't throw everyone in a trial. Filtering based on who is most motivated to go through the process makes sense.
The opposite, where oncologists enthusiastically convey the news of trials that probably won't work and offer false hope, isn't great.
The whole point of the trial is to get to the point where we know we can recommend this for more people.
You faith in the medical profession is wildly excessive. I was just given someone else’s xray and someone else’s IV
You can spend WAY more time running things down than any doctor.
2) Medical trials are notoriously bad about being findable.
We have had several articles on HN about this. There are actually businesses that take money to chop through some of the red tape for you.
3) The average reader of HN has a much different skill set than the average doctor.
Certainly, the doctor doesn't have the same ability to crunch through data like programmers do. Nor are they likely as focused.
4) Doctors have a spectrum from excellent to sub par just like all humans.
The treatments are damn near miracles--when they apply. The other problem is that cancer, just like any life form, will mutate over time and generally becomes resistant to the treatment.
“Maus walked me through some of the steps needed to create CAR-T cells for the trial. We started with the room where the DNA instructions that are added to the T cell’s genome are written. […] We went on to the lentiviral-production room, where technicians create viral vectors carrying this DNA. From there, we moved to the tissue-culture room, where the vector is mixed with normal T cells to create the CAR-T. Finally, we visited the immune-monitoring part of the lab, where lab techs assay blood draws and other samples from patients, looking for proof that the CAR-T cells have made it to their targets.”
“Jennifer Wargo, a professor of genomic medicine at MD Anderson, referred to the cost of immunotherapy treatments as ‘financial toxicity.’ The patent for June’s CAR-T therapy for leukemia is owned by Novartis, and the median cost for the treatment is $620,000. Even if drug companies don’t try to profit from these therapies, the process is inherently labor-intensive: T cells have to be removed from the patient’s own blood, genetically altered, then reinfused. It’s difficult to determine where economies of scale might kick in.”
Given the audience of this site, perhaps "IT" isn't the best acronym to use here.
TKIs are for very rare lung cancers but they're quite effective for late stage cancer patients whom have the right type of tumor mutations.
Yeah. I'm dying of a squamous cell carcinoma infestation: https://jakeseliger.com/2023/07/22/i-am-dying-of-squamous-ce... and the most recent clinical trial drug that was working, has stopped working: https://jakeseliger.com/2024/05/20/in-which-the-antibody-dru....
One of the options for a next trial is from TScan, "A Basket Study of Customized Autologous TCR-T Cell Therapies." https://www.clinicaltrials.gov/study/NCT05973487?term=tscan0.... On the one hand, it looks very promising; on the other hand, lots of promising treatments fail during dose-escalation, first-in-human trials. To my knowledge, the first humans dosed with TScan's TCR-T therapy got it a few months ago.
I got lucky, too, in that a slot for BGB-A3055 with Tislelizumab, an immunotherapy drug and trial, opened up at NEXT Oncology-Dallas: https://clinicaltrials.gov/study/NCT05935098?term=BGB-A3055&.... One challenge, however, is that I received a bispecific antibody called petosemtamab from Sept 2023 to March 2024, then PDL1V (an antibody drug conjugate), and they're considered immunotherapies, so there's a question of whether continuing to pursue immunotherapies makes sense. By now the number of lines of therapy I've gotten make me ineligible for some trials: https://bessstillman.substack.com/p/the-drugs-killing-dying-..., and I've also blown through the more promising drugs for what is a difficult-to-treat cancer type.
It took just five years to get from their first promising results to FDA approval
This sentence is insane. "Just?" It should be happening in months, not years. These are people with fatal diagnoses. Having the FDA hold up therapies like this is criminal.
Aka one hell of a tough call
The solution for terminal cancer patients is to let them use any experimental services they please.
Next.
In the best case, you end up bankrupt. In the worst case, you end up bankrupt and dead.
This is only a slightly more extreme version of the Sackler problem.
Deregulation sounds great if you believe everyone is logical and has accurate information to make decisions for themselves.
I'm sure there must be a much better solution than what we've got for the people who are dying.
But I doubt the answer is to just let drug companies sell anything to anyone and make Medicare pay for it.
That was like Robert Stack, in Joe Versus the Volcano[0].
We pay people to figure out that this is happening (the police), then we prosecute the doctor and if that is what happened we hit the doctor with the full force of law, and they never walk as a free person ever. We also do the same thing with those who bribed the doctor and they also never walk as a free person again.
What you describe already crosses into criminal conduct. We do not need FDA approval process to prosecute it. In fact I’m not sure how the FDA approval of the drug prevents it in your opinion.
Does it? How many people from Purdue Pharma went to prison exactly?
There are no consequences for the behavior you describe regardless of whether it's technically illegal.
Have they told the patient that they are dying?
Treatments should have solid evidence they improve overall survival when compared against the best treatments available today, and unfortunately too many studies either aren't aiming at revealing that info, and/or are comparing against inferior treatment options.
You might as well be saying "what happens if some improbable risk of X exists in this very unusual context". That's existence, especially in complex and fraught situations. You can't completely regulate it away and especially not if the regulations themselves can cause much greater harm in the much, much more probable situation of patients who are already dying being willing, as human beings with autonomy, to try something personally risky.
Deregulation shouldn't and doesn't depend on the world being one of everyone being logical and always having accurate information. Those two conditions don't exist in the human world at all times, period. Furthermore, the exact same problem applies to regulators and legislators as well, whose poorly reasoned decisions can cause broad harm too. Making a lack of perfect information and attendant risk into the key basis for onerous regulations is bad reasoning with sometimes grotesque consequences, particularly in situations where the regulations are known to cause suffering to people in extremes (as is the case with denying risky treatments to those who are in any case at death's door..
Also, very basic but obvious: anyone in the extreme situation of having a doctor suggest a very experimental treatment can go and get a second opinion from another doctor.
It's a largely different clinical and treatment situation from specific cases in which people are genuinely, terminally ill and a genuine though dangerous treatment option exists that might save their very lives. The Sackler case is a valid and powerful criticism of medical/pharma dishonesty, but it's extremely unfair to desperate patients that it be used to prevent them from having the autonomy over their own bodies and literal chance at life that they might legally be allowed to pursue.
Also worth noting that even in the market for prescription opioids, the Sackler case has more recently been used to wrongfully prevent patients who are in deep pain from obtaining a drug that provides needed relief despite its addiction dangers. So even here, obsessions about malpractice are hurting legitimate use.
If it's experimental it shouldn't be expensive. In fact it probably should be free until it's approved as effective. So with that out of the way, what are your other objections? (I am genuinely interested)
But the pharmaceutical companies really want to prove that their drugs work. If their drug doesn't work, nothing is lost or gained by having people try it.
If the drug does work, but the study of it is confounded by giving it to people in a haphazard way, such that we don't know if it works--- more people suffer.
It sucks, but most things don't work. Occasionally people are screwed by not being able to get into a trial for something that might have saved them or lengthened their life. But much more often they're spared false hope and suffering from side effects, and we end up with trials that we can trust.
The incentives of the FDA are unfortunate. If they don't approve a drug that would have saved 100k people there is no bad press for those 100k deaths. But if they approve a drug that kills 1k people there is a lot of bad press.
So they have strong incentives to not approve anything unless absolutely needed.
Most competent doctors will explain WHY they cannot prescribe something, and it's usually more specific such as "your liver is failing and this drug will accelerate that process, perhaps we can find something else".
https://www.fda.gov/patients/learn-about-expanded-access-and...
There isn't really a single baseline untreated group. For a comparison between groups to be valid, all groups must be obtained by unbiased random sampling of the same population. In a clinical trial, that population is the patients served by the participating clinical center. Patient characteristics differ by time and place.
You can try to retrospectively construct a control group using a case control study design, but then you're getting to pick what control group to use, so the results are less reliable (more opportunity for human bias).
Unless a treatment is both miraculous in effect and works for everyone, it's hard to figure out if it works.
Yup. It's worth noting that "all or none" evidence is still considered category 1 evidence on many scales. (If you treat a group where all would be expected to die, and some survive... or a group where many would be expected to die, and all survive). It's only valid for the most dramatic effects, but you don't need randomization. During a safety trial you might come up with "all or none" evidence if your effect is strong enough.
But otherwise, you're going to need to compare the treatment to something else. There's no ability to magically draw the exact same population from some earlier trial.
It is comprised of very knowledgeble patients (like you) that are very actively involved in their treatment. I have been researching a lot of these resources due to my mother's condition, so feel free to let me know if you'd like to do some knowledge sharing.
Wish you all the best on your journey. God bless.
Would love to hear about any more recommendations you or OP might have for good forums etc.
I wish you all the best in your trial, I wish that it's effective and may the side effects spare you !
I worked in specialty pharma for 6 years and the ability to expand capacity is very limited, a rock star drug will take 2-5 to reach full production.
Sometimes people see Covid / Ozempic and think it would be easy to scale like that, but the requirements and challenges are completely different.
It's just all really hard. I try to keep present when spending time with her.
At this point the best we are hoping for is a few more years but understand if it doesn't work out. It is still wild to see where we are going. While I am skeptical of many technological claims that get thrown around nowadays, medical advances are still plodding along wonderfully. Even if at times it can be two steps forward, one step back.
>> The FDA indicated that patients and participants in clinical trials receiving CAR T-cell therapy should be monitored life-long for secondary malignancies.
https://www.onclive.com/view/fda-requires-boxed-warning-for-...
Regarding solid tumors, I've only hear about T-cell exhaustion, but CAR-T solid tumor trials are ongoing:
https://med.stanford.edu/cancer/about/news/car-t-solid-tumor...
>> Although CAR T-cells directed toward the HER2-expressing tumors have been extensively studied in clinical trials, safety concerns have emerged following the death of a CRC patient who received 1×1010 third-generation HER2-CAR T-cells.
It's quite expensive and doesn't always work. We have predictors of whether it works well or not, but nothing has stuck. It's very hard because cancer is hard and immune system is hard, and this is both.
THis whole thing about "immunotherapy is new and has bugs to figure out" is half true, but hell, if "bugs" mean that it doesn't work, the whole reason immunotherapy exists is because the things that came before also had these "bugs" ie people dying.
Every cancer is different. Every cancer is different in every different person. THere are common trends, common genes, common themes, absolutely, but every cancer is different just like every person every face is different. At best you can get a common drug targeting common genes and common themes, just like you could target people with brown hair, but if you happened to have blonde hair you're out of luck until they cook up a solution for that. This is the nature of cancer and where there is no universal cure.
also this board is pretty dang comp sci heavy, and comp sci and physics the instinct is 1000% dunning kruger within the realm of biology or other extraneous inferior-appearing fields. BIology is the most rabbit hole ridden field. The rabbit holes have rabbit holes, and they have their own rabbit holes. You're thinking about cancer but maybe it relates to some evolutionary resistance that was necessary 200 million years ago, and that relates to a biochemical pathway protein binding side. It's a polymath's wet dream really. So it's important not to hand wave or give airs of understanding it. I've been specializing in the area for many years and I can say that nobody understands it really, other than that it works sometimes with some various correlates of when it works. Like most parts of bio, people will specialize in one compenent of the system or one pathway, not the system as a whole. People who claim to capture the system as a whole kinda do interesting things but they don't have the detailed big picture, more like various correlates that are frought with confounders
seems like it's almost the same methodology in making the immune system target specific proteins.
https://ufhealth.org/news/2024/uf-developed-mrna-vaccine-tri...
https://www.mskcc.org/news/can-mrna-vaccines-fight-pancreati...
I don't think anybody thinks it "didn't work out". It's still actively ongoing:
https://www.mdanderson.org/newsroom/md-anderson-curevac-ente...
https://investors.modernatx.com/news/news-details/2023/Moder...
(from 2021):
https://link.springer.com/article/10.1186/s12943-021-01348-0...
https://link.springer.com/article/10.1186/s12943-021-01348-0
You'd be surprised at the number of cancer treatment studies that are deeply flawed:
- Positive effects may have a low confidence due to small sample size, the joke is that if you can fit the laser pointer between the lines it's considered a success. Cancer is a very tough disease and sometimes positive results are due to noise in the dataset.
- Some studies don't consider overall survival (important because you might not die of cancer but you might die sooner from a side effect like Parkinson's caused by the treatment). See mammograms and colonoscopies for treatments that look like they are almost entirely ineffective.
- Don't compare against the standard of care (its easier to show positive results if you aren't using the best treatments available)
- Allow for self selection (the treatment isn't blind or double blind and people drop out of the control group, skewing the results)
Imo he's an excellent source of the latest data driven results related to cancer and other treatments.
It is possible you are conflating the rise of over-diagnosis, and mis-diagnosis from improvements in imaging, and the consequent rise in colonoscopies and removal of polyps.