[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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