[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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