[HN Gopher] Immunotherapy Is Changing Cancer Treatment Forever
___________________________________________________________________
Immunotherapy Is Changing Cancer Treatment Forever
Author : bookofjoe
Score : 306 points
Date : 2024-07-15 17:41 UTC (1 days ago)
(HTM) web link (nymag.com)
(TXT) w3m dump (nymag.com)
| bookofjoe wrote:
| https://archive.ph/csOhz
| jseliger wrote:
| _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 wrote:
| 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.
| WithinReason wrote:
| It's a real life Trolley Problem
| panosfilianos wrote:
| 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 wrote:
| Except they don't know if either they or the cancer dies
| in either switch state.
| amarant wrote:
| It's Schroedinger's trolley, basically.
|
| Aka one hell of a tough call
| ImHereToVote wrote:
| 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.
| simpaticoder wrote:
| Yes it's strange to tell a dying person "this drug is too
| dangerous to try because it may kill you".
| onlyrealcuzzo wrote:
| 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.
| ChrisMarshallNY wrote:
| _> 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
| krisoft wrote:
| > 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 wrote:
| > 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 wrote:
| > How many people from Purdue Pharma went to prison
| exactly?
|
| Have they told the patient that they are dying?
| willmadden wrote:
| 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_ wrote:
| 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.
| southernplaces7 wrote:
| >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 wrote:
| 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 wrote:
| 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.
| m348e912 wrote:
| >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 wrote:
| Nothing is free, including the clinical trials, which are
| funded often by the government.
| tekla wrote:
| you missed the second part of that sentence. "it may also
| kill you in ways that is even worse than your current
| prognosis"
| BurningFrog wrote:
| 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".
| d1sxeyes wrote:
| 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".
| MaxBarraclough wrote:
| I don't know anything about this, but jseliger
| specifically said it was the FDA who are responsible for
| these delays.
| mlyle wrote:
| 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 wrote:
| 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.
| mechagodzilla wrote:
| 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 wrote:
| Especially when, if that were possible, it would be hard
| to get people enrolled in trials to show any new drug
| actually did work.
| adamredwoods wrote:
| 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".
| pkaye wrote:
| There is the "right to try" act in the US.
|
| https://www.fda.gov/patients/learn-about-expanded-access-
| and...
| drewg123 wrote:
| It seems like the drug maker needs to participate in the
| program. What is the rate of participation?
| adamredwoods wrote:
| I believe patients need a doctor to advocate for them.
| w10-1 wrote:
| 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 wrote:
| 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 wrote:
| > 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 wrote:
| > 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 wrote:
| 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 wrote:
| 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 wrote:
| 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.
| ChrisMarshallNY wrote:
| Coming from Cancer Alley (Long Island, New York), I have been
| watching people battling cancer for 34 years. I wish you the
| very best.
| nick__m wrote:
| 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 !
| bearjaws wrote:
| 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 wrote:
| Pembrolizumab and the like scale just fine.
| xivzgrev wrote:
| 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.
| DonsDiscountGas wrote:
| 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)
| cdolan wrote:
| Is there anything like this for ovarian cancer?
|
| Nearing the end of life for a family member
| dotcoma wrote:
| Maybe this can help. https://www.clinicalnet.com/
| melling wrote:
| 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, ...
| toomuchtodo wrote:
| 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 wrote:
| 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...
| linearrust wrote:
| 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 wrote:
| > 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 wrote:
| > 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.
| ClumsyPilot wrote:
| > 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
| bsder wrote:
| 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.
| y-curious wrote:
| 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 wrote:
| Since you're knowledgeable in the field, I have a question:
| what makes immunotherapy more inherently expensive compared
| to other options?
| pinewurst wrote:
| Because each patient's treatment has to be individually
| created for them.
| moshun wrote:
| This seems like a space ripe for intelligent robotics
| automation. Detailed, precise and laborious requiring
| years of not decades of technical expertise.
| becurious wrote:
| Look at what Cellares is doing. Building a manufacturing
| cell called the shuttle.
| cactusfrog wrote:
| 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.
| mahkeiro wrote:
| 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 wrote:
| 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."
| littlestymaar wrote:
| 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.
| robertlagrant wrote:
| 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.
| shiroiushi wrote:
| >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.
| Raydovsky wrote:
| 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.
| garbageman wrote:
| 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.
| vondur wrote:
| Looks like doctors were able to treat brain cancer with a mRNA
| derived vaccine:
|
| https://ufhealth.org/news/2024/uf-developed-mrna-vaccine-tri...
| jsperx wrote:
| 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...
| adamredwoods wrote:
| 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
| mcbain wrote:
| One big trial still going:
| https://clinicaltrials.gov/study/NCT03739931
| rafaelero wrote:
| They do work, mainly for keeping a remissed cancer at bay.
| Kalanos wrote:
| Yet investors and big pharma are both running away from immuno-
| oncology
| mettamage wrote:
| Why? Do you have some sources I could dig in to?
| bitwize wrote:
| The usual reasons: prolonged treatment is more profitable
| than a cure.
| biofox wrote:
| This doesn't apply when talking about terminal diseases
| like advanced cancer. Dead patients are the least
| profitable of all.
| rickydroll wrote:
| 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 wrote:
| This is not true at all.
| Kalanos wrote:
| 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.
| bollloga wrote:
| Could this be helpful for neuroendocrine cancers?
| wwarner wrote:
| Wonderful article. I'm seeing two Nobels awarded for research
| into immunotherapy. Best of all, immunotherapy probably saved my
| sister from stage 4 cancer.
| duban wrote:
| 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.
| elromulous wrote:
| 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.
| 01100011 wrote:
| 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 wrote:
| opdualag? I know someone who took it with lasting side
| effects.
| mcbain wrote:
| 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 wrote:
| 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 wrote:
| 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 wrote:
| "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 1x1010 third-generation HER2-CAR T-cells.
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10067596/
| borbulon wrote:
| 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.
| adamredwoods wrote:
| https://www.onclive.com/view/fda-requires-boxed-warning-for-...
| aaronblohowiak wrote:
| I applaud your courage. Take videos for your kids.
| low_tech_love wrote:
| 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.
| throwaway7ahgb wrote:
| 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.
| whythre wrote:
| Telling stories about who you are seems valuable. I
| almost think tying recordings to specific life events
| might be a mistake.
| borbulon wrote:
| 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.
| takinola wrote:
| 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 wrote:
| I wish you could remember more, I'd like to listen to
| that
| AlexErrant wrote:
| Possibly not what OP was thinking of, but maybe this one
| https://www.thisamericanlife.org/283/transcript
|
| Ctrl+f "video"
| whythre wrote:
| 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.
| beardface wrote:
| 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.
| fakedang wrote:
| Sorry for being too direct and perhaps offensive, but I'm
| curious. Was the cancer detected much later? I'm assuming that
| if it were caught in the early stages, you might have been able
| to get treated with trastuzumab.
| DaoVeles wrote:
| 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.
| chmorgan_ wrote:
| 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.
| thenerdhead wrote:
| https://www.panaccindex.info/p/profile-ucsfs-vinay-prasad
| rob74 wrote:
| So, a COVID denialist/anti-vaxxer trying to find a new field
| of activity?
| ggm wrote:
| 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 wrote:
| 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.
| noobermin wrote:
| 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.
| yread wrote:
| 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
| bettercallsalad wrote:
| Is there any potential for immunotherapy for stage IV metastatic
| castration resistant prostate cancer?
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