[HN Gopher] Immunotherapy Is Changing Cancer Treatment Forever
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       Immunotherapy Is Changing Cancer Treatment Forever
        
       Author : bookofjoe
       Score  : 159 points
       Date   : 2024-07-15 17:41 UTC (5 hours 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.
        
               | 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.
        
             | 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.
        
             | 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.
        
           | 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.
        
         | nullserver wrote:
         | There's a lot of studies showing that ivermectin is great for
         | many kinds of cancers.
         | 
         | If someone doesn't have anything to lose, might be worth
         | considering
        
           | staunton wrote:
           | Can you link to any such studies?
        
           | pfdietz wrote:
           | I'm pretty sure there's no real study that says any such
           | thing, although I would not be surprised if you could find
           | some garbage pseudoscience saying otherwise.
        
           | mjfl wrote:
           | Ivermectin is an anti-parasitic that primarily targets worms
           | and other invertebrates. It blocks an invertebrate-specific
           | receptor, and is not known to have any other significant
           | targets. It's great for that, and worthy of a Nobel prize.
           | But it's not miraculous Jesus nectar.
        
         | 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.
        
       | 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...
        
       | 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.
        
       | bollloga wrote:
       | Could this be helpful for neuroendocrine cancers?
        
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