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Immunotherapy Is Changing Cancer Treatment Forever

jseliger
44 replies
23h56m

The biggest question in oncology today is whether this approach could also be used for solid tumors

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.

jonny_eh
35 replies
23h48m

And they're slow to avoid approving dangerous treatments, but that's absurd since the patients are already dying. The risk of not approving needs to be taken into account.

simpaticoder
21 replies
23h26m

Yes it's strange to tell a dying person "this drug is too dangerous to try because it may kill you".

onlyrealcuzzo
11 replies
23h24m

Okay - but what happens when your doctor is getting bribed to say you're dying to get you to try expensive experimental drugs with no evidence of working?

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.

southernplaces7
2 replies
16h17m

Okay - but what happens when your doctor is getting bribed to say you're dying to get you to try expensive experimental drugs with no evidence of working?

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.

noobermin
1 replies
11h12m

This isn't an improbable situation. They literally mentioned the Sackler family, which is a real world example of corruption is medicine of the type they're talking about.

southernplaces7
0 replies
5h22m

The Sackler's company bribed and "financially encouraged" doctors into over-prescribing opioids to millions of people who weren't necessarily mortally ill and with lesser individual risk of those people dying from these prescriptions.

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.

krisoft
2 replies
20h47m

what happens when your doctor is getting bribed to say you're dying

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.

dontlikeyoueith
1 replies
18h51m

What you describe already crosses into criminal conduct.

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.

krisoft
0 replies
17h52m

How many people from Purdue Pharma went to prison exactly?

Have they told the patient that they are dying?

m348e912
1 replies
14h53m

Okay - but what happens when your doctor is getting bribed to say you're dying to get you to try expensive experimental drugs with no evidence of working?

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)

noobermin
0 replies
11h11m

Nothing is free, including the clinical trials, which are funded often by the government.

willmadden
0 replies
20h30m

No, medicare shouldn't pay for it, but it should be completely legal for patients to take whatever drug or procedure they want, and for startups to provide those drugs and services. The medical industry in the United States is a gate kept, over-credentialed, bureaucratic mess.

chmorgan_
0 replies
17h8m

This is an understated reality of the situation. Patients are already able to receive treatments with experimental drugs. It's the "forcing medicare and insurance companies to pay for it" part that's not a good idea, especially considering that most of these treatments may be worse than the current ones.

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.

ChrisMarshallNY
0 replies
23h12m

> but what happens when your doctor is getting bribed to say you're dying

That was like Robert Stack, in Joe Versus the Volcano[0].

[0] https://www.youtube.com/watch?v=oAB9Y2CVqZU

BurningFrog
4 replies
22h59m

It's really something like "this drug is too dangerous to try because if it kills you we will get a lot of bad PR".

MaxBarraclough
2 replies
22h51m

I don't know anything about this, but jseliger specifically said it was the FDA who are responsible for these delays.

mlyle
0 replies
18h47m

So, here's the thing-- drugmakers can get compassionate use exceptions.

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.

BurningFrog
0 replies
16h18m

Yes, I do mean that FDA is worried about getting bad PR.

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.

d1sxeyes
0 replies
22h53m

It’s also a bit of “if you die anyway even if you take our drug, you screw our numbers, so we don’t let folks take it if they’re too ill”.

mechagodzilla
1 replies
22h53m

There is an additional problem in that you want to avoid having people try to sell snakeoil to the desperate because "who knows, it might work."

pfdietz
0 replies
21h58m

Especially when, if that were possible, it would be hard to get people enrolled in trials to show any new drug actually did work.

tekla
0 replies
23h14m

you missed the second part of that sentence. "it may also kill you in ways that is even worse than your current prognosis"

adamredwoods
0 replies
21h29m

I think it's better to understand why a pharmacist or oncologist will not prescribe medicine that could kill a patient, due to either the Hippocratic oath or through malpractice.

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".

WithinReason
4 replies
23h39m

It's a real life Trolley Problem

panosfilianos
2 replies
23h35m

Right to try makes this a variation of the Trolley Problem, because the person to pull the lever is the same person that's tied to the tracks.

klyrs
1 replies
23h25m

Except they don't know if either they or the cancer dies in either switch state.

amarant
0 replies
21h43m

It's Schroedinger's trolley, basically.

Aka one hell of a tough call

ImHereToVote
0 replies
23h23m

The solution to the Trolley Problem is to perform a "slipping the switch" maneuver.

The solution for terminal cancer patients is to let them use any experimental services they please.

Next.

w10-1
3 replies
22h27m

There's another difficulty: to get the numbers needed to validate that a drug works, an equivalent large number of people need to enter the trial in the non-treatment arm, typically foregoing other treatment. Many people refuse to join trials for this reason, and that contributes to the delays in completing trials with sufficient power.

smegger001
2 replies
21h49m

I get the why we in a ideal experiment would like to have a control group but these are human livesvnot rats in lab, so why does every trial need a new control group? If we already know what a baseline untreated group looks like why cant we just compare new drug test to a know control from previous trials thus reducing the need for more dying?

jpeloquin
1 replies
20h5m

If we already know what a baseline untreated group looks like

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.

mlyle
0 replies
18h51m

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.

drewg123
1 replies
21h41m

It seems like the drug maker needs to participate in the program. What is the rate of participation?

adamredwoods
0 replies
21h37m

I believe patients need a doctor to advocate for them.

drewg123
0 replies
21h39m

Has anybody ever just straight up stolen a drug from a clinical trial and had it save their life? If there was ever a case for jury nullification..

panosfilianos
1 replies
23h36m

This community may be of interest to you: https://community.cancerpatientlab.org/

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.

jsperx
0 replies
22h4m

Thank you for this, I have an extremely rare subtype of sarcoma and it’s been tough to a) find any research about it specifically and b) find high-quality resources about state of the art treatments and interventions that aren’t like, Facebook groups where people post wacky articles about homeopathic stuff or whatever.

Would love to hear about any more recommendations you or OP might have for good forums etc.

bearjaws
1 replies
21h42m

FWIW if the drug was approved faster, most immunotherapies are very hard to scale.

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.

pfdietz
0 replies
21h39m

Pembrolizumab and the like scale just fine.

xivzgrev
0 replies
21h36m

I'm sorry to hear that. My mother in law has stage 4 lung cancer. She has some mutations for which there are targeted treatments, but the cancer mutated in one area. Fortunately there were more treatments for that mutation, but she's had some significant side effects from that one. There's potential clinical trials but there's lots of criteria, some may not even be near by: a lot of noise, not much signal. Every quarter's CT scans might tell us medication has stopped working, and she needs to start chemo (with the side effects/lower QOL).

It's just all really hard. I try to keep present when spending time with her.

nick__m
0 replies
22h30m

Thanks you for posting your story in details, as someone who's wife had oligometastasis on her spine from breast cancer (nothing compared to you, but incredibly stressful nonetheless) you give me hope that when Ribociclib stop working, M.A.I.D. is not the next step.

I wish you all the best in your trial, I wish that it's effective and may the side effects spare you !

DonsDiscountGas
0 replies
21h26m

It's not possible to evaluate efficacy any faster than that. I suppose we could just let everything on the market and see what happens, but it would still take years to accumulate efficacy data. So you'd just be left with preclinical data which isn't that useful (if it was the failure rate of oncology clinical trials wouldn't be so high)

ChrisMarshallNY
0 replies
23h11m

Coming from Cancer Alley (Long Island, New York), I have been watching people battling cancer for 34 years. I wish you the very best.

cdolan
20 replies
22h43m

Is there anything like this for ovarian cancer?

Nearing the end of life for a family member

y-curious
10 replies
20h1m

I actually wrote my thesis on this. Ovarian is very commonly studied for immunotherapy, but there isn't anything out there outside of the clinical research realms. The data is pointing more and more to solid cancers being much less responsive to immunotherapy than blood cancers. Unfortunately, I don't have good news for you here. We are probably 30 years away from having an IT medicine that doctors prescribe regularly. And even then, it will be insanely expensive

littlestymaar
8 replies
19h51m

Since you're knowledgeable in the field, I have a question: what makes immunotherapy more inherently expensive compared to other options?

pinewurst
4 replies
19h41m

Because each patient’s treatment has to be individually created for them.

moshun
2 replies
19h15m

This seems like a space ripe for intelligent robotics automation. Detailed, precise and laborious requiring years of not decades of technical expertise.

cactusfrog
0 replies
14h53m

Biochemical engineering exists as a discipline and focused on “scale up” of production problems like these. Robots are involved, but most of the time the process is modified to a more stable one.

becurious
0 replies
17h22m

Look at what Cellares is doing. Building a manufacturing cell called the shuttle.

mahkeiro
0 replies
11h4m

They are many different kind of immunotherapies, not all of them have to be patient specific. For cell or vaccine therapies a lot work is currently done to create "off the shelf" treatment which may ease the issue with car-t treatments.

jsperx
2 replies
19h28m

The article has a couple paragraphs about the complexity involved in fabrication and how labor intensive it is:

“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.”

robertlagrant
0 replies
7h46m

Half of that second paragraph seems to not belong there. Why rebrand "expensive" as "financial toxicity"? Why is profit bad when companies' losses are fine? It seems very strange.

littlestymaar
0 replies
10h1m

Yeah, but that opens many more questions than it answers: this $620 000 figure cannot come out of labor intensity alone, as it represents the cost of thousands of work hours (literally a dozen of doctor full time for a month, or at least 50 well paid specialized technicians working for an entire month on each patient treatment) yet the process described in the text doesn't seem to match this level of labor.

shiroiushi
0 replies
14h9m

We are probably 30 years away from having an IT medicine that doctors prescribe regularly.

Given the audience of this site, perhaps "IT" isn't the best acronym to use here.

linearrust
4 replies
21h8m

If there was, your family member's oncologist would have informed your family member of it.

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.

el_benhameen
1 replies
20h47m

If there was, your family member's oncologist would have informed your family member of it.

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.

[0] https://jakeseliger.com/

mlyle
0 replies
19h52m

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.

bsder
0 replies
20h9m

1) To your oncologist, this is Tuesday. For you, this is the most important thing in your life.

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.

ClumsyPilot
0 replies
20h38m

If there was, your family member's oncologist would have informed your family member of it.

You faith in the medical profession is wildly excessive. I was just given someone else’s xray and someone else’s IV

toomuchtodo
0 replies
21h30m

Are you located anywhere near the University of Texas? There appears to be a protocol combining etigilimab and nivolumab.

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)

mjfl
0 replies
21h13m

My condolences... You should consult with their oncologist, but you could ask for Keytruda treatment. You should be aware that the immune response to a late stage cancer that results could also be dangerous, including high fever and delirium... Best wishes to you and your family...

melling
0 replies
21h33m

I’m an amateur but have read a bunch about the new targeted therapies, like immunotherapy. Immunotherapy seems to only work in a small percentage of tumors with a lot of mutations. It’s easier to get your immune system to attack those.

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, …

borbulon
10 replies
18h14m

I was recently released from a clinical trial because of too many “newly measurable” areas of tumor. I was offered CAR-T but was told that it comes with a high risk of possibly fatal infections and is not guaranteed to work at all for my cancer (HER-2 positive lung cancer, stage 4). I turned it down. I have a wife and 3 kids, I’d rather spend an unknown amount of time being fully present with them than risk my life today.

aaronblohowiak
7 replies
17h21m

I applaud your courage. Take videos for your kids.

low_tech_love
6 replies
7h26m

Is this really a good idea? I’ve been thinking about doing this for a while, but a part of me tells me it’d just be weird and morbid for them, and maybe interfere in their ability to let me go and live their life to the fullest.

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.

takinola
2 replies
4h8m

There's an old episode of RadioLab or This American Life (I can't remember which) that explores this very topic. If memory serves, there was a woman who lost her mum at an early age but her mum recorded videos to be shared with her at certain points in her life (birthdays, graduations, etc). I recall her mentioning she came to dread those events knowing she would have to relive losing her mum by watching the video. I can't recall if she felt it was a net positive or not.

borbulon
1 replies
2h31m

I wish you could remember more, I'd like to listen to that

whythre
0 replies
6m

I have located different bits of old media recorded of my grandfathers on both sides. One example being a long form interview about my maternal grandfather’s Korean War experiences. I enjoy watching or listening to these from time to time. If my father passed early I am sure I would’ve been very grateful to hear his words too.

throwaway7ahgb
0 replies
6h41m

Don't make it morbid then? Just talk to them and let them get to know who you are.

That itself is incredibly difficult as most people can't describe who they are beyond their name and title.

borbulon
0 replies
4h52m

The biggest thing people who have lost someone close to them have to say is that they start to forget what the person looked like and sounded like. I am doing it - I think if you keep it casual, like "hey, I was just thinking about you and the day you graduate high school, and I'll bet....." kind of thing, you're making it less morbid.

beardface
0 replies
9h15m

My Mum went through CAR-T for lymphoma earlier this year. It's a brutal therapy but can offer benefits in the long term.

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.

Raydovsky
6 replies
22h28m

Anybody know why MRNA cancer vaccines didn't work out?

seems like it's almost the same methodology in making the immune system target specific proteins.

rafaelero
0 replies
59m

They do work, mainly for keeping a remissed cancer at bay.

jsperx
0 replies
22h10m

As somebody who unfortunately has a Stage IV diagnosis I have been researching mRNA and there have been promising results such as the MSK pancreatic study below, but still much to be ironed out — they had half the participants get a response but the other half nothing, even though each treatment was individually targeted and customized. They are doing a larger study now to try to see what other factors may be at play.

https://www.mskcc.org/news/can-mrna-vaccines-fight-pancreati...

garbageman
0 replies
22h25m

They might but if I recall MRNA stuff is pretty new - and getting the clinical trials through the entire process and approval takes quite a long time.

adamredwoods
0 replies
18h20m

mRNA vaccines need a target, and if there is a target, there are several approaches that already do this (anti-body drug conjugates), and sometimes work, sometimes doesn't.

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

Kalanos
6 replies
22h7m

Yet investors and big pharma are both running away from immuno-oncology

mettamage
3 replies
21h52m

Why? Do you have some sources I could dig in to?

bitwize
2 replies
21h27m

The usual reasons: prolonged treatment is more profitable than a cure.

biofox
1 replies
21h6m

This doesn't apply when talking about terminal diseases like advanced cancer. Dead patients are the least profitable of all.

rickydroll
0 replies
20h39m

My brother committed suicide last February. His death was profitable for the funeral home. Anyone who manipulates a 90-year-old grieving mother deserves burn in several circles of hell.

adamredwoods
1 replies
21h26m

This is not true at all.

Kalanos
0 replies
5h14m

My sources are leading immuno-oncology pharma R&D teams and oncology VCs as recently as this week. I am launching an immuno-oncology therapeutics company.

duban
5 replies
18h55m

Immunotherapy saved my life, but sadly also made me an insulin dependent type 1 diabetic. (See https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10083744 for more info about this side effect)

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.

01100011
2 replies
14h0m

Yep, it wrecked my friend's thyroid and adrenals. I don't know what the drug was, but it was immunotherapy for stage iv melanoma.

Sparkle-san
1 replies
13h27m

opdualag? I know someone who took it with lasting side effects.

mcbain
0 replies
12h46m

There's a bunch of different immuno types for melanoma (and other cancers). That one is a combo of nivolumab (aka Opdivo) and relatlimab.

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.

noobermin
0 replies
11h29m

Cancer really sucks like that. A lot the treatments definitely keep you alive and even cure you but leave you with nasty side effects. Oncologists measure changes in Quality of Life (QoL). When you have some kpi that attempts to model something as subjective as your quality of life you know it's quite bad already.

elromulous
0 replies
18h51m

Of course on a completely different level, but I think this will be similar to how e.g. antibiotics or biologics have played out. First generation has awful side effects as researchers focus on getting anything to work at all. Then once a certain baseline of efficacy is reached, they can focus on reducing side effects.

chmorgan_
3 replies
16h58m

I follow Vinay Prasad MD (https://www.youtube.com/@vprasadmdmph), who does a lot of research related to medical studies and methodology, lots of cancer related ones as that's an area where he works.

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.

rob74
0 replies
11h43m

So, a COVID denialist/anti-vaxxer trying to find a new field of activity?

ggm
0 replies
14h21m

I believe Mammograms and Colonoscopies are diagnostic techniques not treatments per se.

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.

seizethegdgap
2 replies
16h48m

My wife has Stage 2(B?) triple negative breast cancer (TNBC). Her treatment regiment includes Keytruda (pembrolizumab) once every 21 days. There was a full trial she was told about that is exploring using pembrolizumab entirely without chemo for TNBC. It's incredible that we might soon have at least one cancer that we might not need chemo to treat.

yread
0 replies
11h15m

There are a few de-escalation trials where patients with high amount of lymphocytes in tumor associated stroma don't need to get chemo, even for stage 2 and 3 TNBC

noobermin
0 replies
11h25m

People are now taking TKI inhibitors as first line treatments. It doesn't really cure you, but given long term stable disease, you could end up with late stage cancer patients who don't need chemo for years.

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.

elromulous
1 replies
18h49m

Can someone explain why it's taken so long to go from the success CAR-T had with non solid tumors, to getting an immunotherapy that indeed is effective against solid tumors?

adamredwoods
0 replies
17h50m

"Success" for CAR-T is hazy, as many participants died from unrealized side effects, including new cancers.

> 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.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10067596/

wwarner
0 replies
19h12m

Wonderful article. I’m seeing two Nobels awarded for research into immunotherapy. Best of all, immunotherapy probably saved my sister from stage 4 cancer.

bollloga
0 replies
19h38m

Could this be helpful for neuroendocrine cancers?

bettercallsalad
0 replies
10h42m

Is there any potential for immunotherapy for stage IV metastatic castration resistant prostate cancer?

DaoVeles
0 replies
17h48m

My father is in his mid 70's with bladder cancer and is now going down the immunotherapy path completely aware that this is still essentially a new thing with bugs to be figured out.

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.