[HN Gopher] Breakthrough drug trial saw cancer vanish in every p...
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Breakthrough drug trial saw cancer vanish in every patient (2022)
Author : wjb3
Score : 98 points
Date : 2024-04-05 19:27 UTC (3 hours ago)
(HTM) web link (www.euronews.com)
(TXT) w3m dump (www.euronews.com)
| qclibre22 wrote:
| 2023 news: original paper :
| https://www.nejm.org/doi/pdf/10.1056/NEJMoa2201445
| dekhn wrote:
| I don't think this is the first study where 12 patients showed
| full remission. Further, you'd expect that to happen _by chance_
| at the scale that we run small trials like this.
| marginalia_nu wrote:
| Flipping 12 coins and having them all land on heads is a 0.02%
| probability event. Cancer spontaneously going into remission in
| a patient is pretty far away from a coinflip.
| dekhn wrote:
| That's true but this is a clinical trial where the patients
| are being treated- the patients were selected according to
| strict criteria, and received other treatments in cancer
| centers. It's not really just "coinflips", it's heavily
| biased coinflips.
|
| Maybe I should have put this in a more productive way: I
| prefer studies that have a large enough n that you can
| actually measure the failure rate. There's a classic
| statistics paper where an operation was done on 3 patients
| and none died- the paper's title is "If nobody dies, is
| everything OK?" and goes into whether you can reliably
| conclude causal effects with very small n.
|
| Further- let's say the drug caused remission in 50% of the
| patients, and the other 50% had spontaneous remission (or
| remissionc aused by other aspects of the treatment). Now it's
| not 1/2 * 12, it's 1/2 * 6 (or whatever base probability you
| want to choose). If you compare that probability to the
| number of people in clinical trials in the US, you would
| expect that after 30-40 years, you'd see at least one trial
| with 12 patients with complete remission.
|
| (I don't actually doubt the drug is effective. We already
| know that. And we already know that studies this small really
| stretch the concepts of significance and causality).
| superb_dev wrote:
| I think most people would prefer a study with more
| participants, but you can't jump to a large human trial
| right away
| dekhn wrote:
| Patient recruitment is hard, but this is a phase II on an
| already approved drug. Typical Phase II has at least 100
| patients.
| readthenotes1 wrote:
| As other people have mentioned, this is just a variation on a
| theme of other successful drugs. It may well be that the odds
| are greater than 50% the way they selected the patients.
|
| There's also publication and hacker News front page bias to
| consider in the odds making as well...
| dekhn wrote:
| I end up seeing a lot of these discussions and you can
| always tell the difference between a person who doesn't
| know much math but works in the field, to somebody who
| knows a lot of math but doesn't work in the field.
| Experience and wisdom matter a lot wrt drug discovery and
| cancer treatment.
| bawolff wrote:
| > Flipping 12 coins and having them all land on heads is a
| 0.02% probability event. Cancer spontaneously going into
| remission in a patient is pretty far away from a coinflip.
|
| You don't actually have to run that many trials before a
| 0.02% liklihood event happens by chance.
| pie420 wrote:
| only 5000 or so trials, easy
| Kalanos wrote:
| It's a checkpoint inhibitor. Those have been used for ~ every
| cancer type for over a decade. Keytruda has been a top-selling
| drug for years.
|
| It looks like this trial was neoadjuvant (before treatment/
| alternative to chemo and surgery), but that's not new either.
|
| immunotherapy typically has much lower _response rates_ though,
| so maybe it 's the mismatch repair selection strategy that's
| novel
|
| at a sample size of 12... they could have gotten lucky
| kjkjadksj wrote:
| Using mismatch repair has been a concept for almost a decade
| now, the initial pd-l1 papers were very much focused on it.
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576142/
| Kalanos wrote:
| thanks. yeah i dunno then
|
| First-line nivolumab metastatic colorectal w MMR:
| https://pubmed.ncbi.nlm.nih.gov/34637336/
|
| first-line keytruda metastatic colorectal w MMR:
| https://www.nejm.org/doi/full/10.1056/NEJMoa2017699
| tyingq wrote:
| I'm no expert, but it says it's Dostarlimab, which is billed as
| a monoclonal antibody. Some googling suggests that monoclonal
| antibodies and checkpoint inhibitors are both immunotherapy
| approaches, but that they aren't the same.
| mcbain wrote:
| They are
| https://en.m.wikipedia.org/wiki/PD-1_and_PD-L1_inhibitors
|
| The hint is the -mab naming.
| pfdietz wrote:
| -ab means it's an antibody. There are many kinds of
| antibodies, not just to those two proteins.
| semi-extrinsic wrote:
| And -mab means monoclonal antibody. But your point still
| stands, there is a huge number of -mab drugs out there
| today.
| pfdietz wrote:
| It's a really great technology, and not just for drugs.
| It deservedly won the Nobel Prize in Medicine in 1984.
| Kalanos wrote:
| checkpoint inhibitors are antibodies
| hentrep wrote:
| For reference, dostarlimab (JEMPERLI) is essentially GSK's
| answer to Merck's pembrolizumab and BMS's nivolumab. Or
| KEYTRUDA and OPDIVO, respectively, if you're in the USA and
| bombarded with pharma ads. All three are monoclonal
| antibodies that block PD-1 on T cells, thereby stimulating
| the body's immune system.
| Kalanos wrote:
| i wouldn't refer to it an an immunostimulant. it prevents
| tumors from hiding.
| adamredwoods wrote:
| The bigger question I have, if these PD-1 blockers all have the
| same method-of-action, why are they showing different results
| for different tumors?
| vikramkr wrote:
| For context, this study was in 2022, this drug had received
| accelerated approval in 2021 and was fully approved by the FDA in
| 2023 for mismatch repair deficient endometrial cancer.
| (https://www.fda.gov/drugs/resources-information-approved-
| dru...).
|
| It's awesome to see the amount of progress in cancer that deeper
| understanding of the disease is bringing. Identifying
| interventions that work in a subset of patients with specific
| mutations, targeting them specifically, using immunotherapies,
| all incredibly cool and impactful.
| ip26 wrote:
| Success with targeted therapy also hopefully paves the way
| towards the understanding we need for generalized solutions.
| davikr wrote:
| I am so excited for the monoclonal antibody revolution of
| Medicine. Here's to them getting cheaper someday.
| namibj wrote:
| How expensive are they to make these days? There's also one in
| progress made from human stem cells that blocks a teeth-
| regrowth-inhibitor, causing mice and ferrets to grow more and
| new teeth.
|
| It should allow human adults to grow new teeth over a period of
| 2~5 years, if removal of the old teeth is surgically assisted
| (the roots are too deep to have it work automatically, thus
| evolution of the blocker). Oh, and it's systemic as I
| understand, so usage would involve pulling all the teeth
| present when starting.
| Terr_ wrote:
| > There's also one in progress made from human stem cells
| that blocks a teeth-regrowth-inhibitor, causing mice and
| ferrets to grow more and new teeth.
|
| That's quite an unexpected mix of optimistic, cute, and then
| disturbing right there.
|
| > Oh, and it's systemic as I understand, so usage would
| involve pulling all the teeth present when starting.
|
| Never mind, fully disturbing now. :P Though I suppose it
| might be interesting for folks who've already lost almost all
| of them...
| mikeInAlaska wrote:
| > How expensive are they to make these days?
|
| A good question, I can't answer. But I can tell you, when my
| daughter had her liver transplant, they gave her an insane
| amount of medications for weeks. They only gave her one shot
| of a monoclonal antibody "Basiliximab". The syringe with it
| was escorted by two guards from the pharmacy.
| knodi123 wrote:
| > The syringe with it was escorted by two guards from the
| pharmacy.
|
| Isn't it only, like, a few thousand dollars? By all means,
| be careful with it, but you don't see teams of guards at
| the apple store escorting hardware to the customer.
|
| Was this maybe earlier in development and the price was
| much higher or something?
| semi-extrinsic wrote:
| A few years ago the pharmacy accidentally keyed in the full
| price for two months (four injectors) of Humira, IIRC it was
| like $3k. This is in Northern Europe, probably it's more
| expensive in the US? Also I don't know if the price has come
| down since.
|
| Of course it's also a price vs volume thing, but I heard a
| while back that scaling up bioreactors is the limiting factor
| for these monoclonal antibodies.
| Terr_ wrote:
| As long as we don't get the cyberpunk dystopian outcomes like
| tailored molecules dumped in the water supply to assassinate a
| specific individual.
|
| > They sent a slamhound on Turner's trail in New Delhi, slotted
| it to his pheromones and the color of his hair. It caught up
| with him on a street called Chandni Chauk and came scrambling
| for his rented BMW through a forest of bare brown legs and
| pedicab tires. Its core was a kilogram of recrystallized
| hexogene and flaked TNT.
|
| -- _Count Zero_ , by William Gibson
| methodical wrote:
| Original HN post on this same subject from 2022:
| https://news.ycombinator.com/item?id=31630679
| dang wrote:
| Thanks! Macroexpanded:
|
| _A cancer trial's unexpected result: Remission in every
| patient_ - https://news.ycombinator.com/item?id=31630679 - June
| 2022 (232 comments)
| aurizon wrote:
| Are we going to see colo-rectal surgeons on the endangered
| species list, not to speak of other cancer specialties?
|
| https://www.youtube.com/watch?v=W2gABYTmXos
| methodical wrote:
| I mean there are more maladies that affect the colon and rectum
| than just colon cancer, so I expect colo-rectal surgeons will
| survive, if with a decline in positions.
| aurizon wrote:
| True, mechanical problems will endure, even if cancer is
| defeated.
| hentrep wrote:
| This is actually one of the goals in colorectal cancer - organ-
| sparing treatment options. In particular, using immunotherapies
| in the neoadjuvant, peri-operative setting has shown tremendous
| benefit in colorectal cancers. Work done by Myriam Chalabi
| (Netherlands Cancer Institute) with the NICHE-1 study [0] and
| Pashtoon Kasi (Cornell) with the NEST-1 study [1] have had
| tremendous impacts for the up to 15% of patients who have
| mismatch repair deficient CRC.
|
| [0] https://ascopost.com/issues/october-25-2022/unprecedented-
| wa... [1]
| https://www.nyp.org/advances/article/gastroenterology/ongoin...
| semi-extrinsic wrote:
| From what I've heard, surgery to treat hand osteoarthritis is a
| dying sub-specialty because the drugs are so effective now (and
| the surgery has never been a very good solution).
| sniperjoe360 wrote:
| Really impressive results. The real victory here wasn't the
| breakthrough drug, which many have pointed out is another flavor
| of PD-1 inhibition (Nivolumab, Pembro) It's the patient selection
| - careful curation of MSI status with Next Gen Sequencing.
| Clinically it has already been implemented and is changing the
| outcomes of thousands of patients every year.
| xk_id wrote:
| * in a 5-10% subset, of a subset, of a subset of cancers.
| hentrep wrote:
| At risk of taking the bait with this flippant comment, I'd like
| to highlight your critique of what others used to long for as
| "targeted therapy" or "personalized medicine". I suppose we
| could always step backward to a world dominated by systemic
| cytotoxic chemo, though. Which, to be fair, still has its
| place.
|
| Cancer tends to evolve at a rate that outpaces treatment
| innovation, and the molecular determinants can be wildly
| heterogenous. For example, a lung cancer patient can have half
| a dozen tumors that all harbor independent oncogenic drivers.
| It is not uncommon for a patient to undergo treatment with a
| target therapy and see complete tumor responses in some
| lesions, while others grow unimpeded.
|
| We did not develop our own code base. Humans are a black box
| and drug development is HARD.
| xk_id wrote:
| It's not a comment on the value of the treatment, the
| headline is just wrong. Saying "cancer vanished in every
| patient" without further qualification is ambiguous, not too
| different from saying "illness was cured in everyone". The
| correct title should have been "Success using a targeted
| anti-cancer therapy".
|
| Btw, there is still research that tries to find a general
| mechanism for interventions. The other day I looked at
| interesting work that hinged the delivery of disruptive
| payload on telomerase activity. Telomerase is expressed
| almost universally in cancer cells and in stem cells;
| therefore somatic cells would be spared, and it's hoped that
| stem cells would be able to recover.
|
| Anyway like you said, both approaches are meaningful, which
| is why it's important to tell them apart.
| ChrisArchitect wrote:
| (2022)
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