7 ms·
Breakthrough drug trial saw cancer vanish in every patient (2022)
- qclibre22 3y ago2023 news: original paper : https://www.nejm.org/doi/pdf/10.1056/NEJMoa2201445 https://www.nejm.org/doi/pdf/10.1056/NEJMoa2201445
- davikr 3y agoI am so excited for the monoclonal antibody revolution of Medicine. Here's to them getting cheaper someday.
- namibj 3y agoHow 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_ 3y ago> 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...
- namibj 3y agoHey, my understanding is that they're initially targeting Japanese ~~elderly who have already lost their teeth~~ children who genetically forgot to grow at least 6 of their adult teeth (1 in 10k affected). (https://uniqa.dental/news/tooth-regeneration-drug-trials-in-japan/ https://uniqa.dental/news/tooth-regeneration-drug-trials-in-...) Also there are many people who have sustained teeth damage bad enough to normally warrant 2+ implants plus fillings for the others, and at that point, it's warranted to think about doing "wisdom teeth removal" for the remaining and growing a new set. It's obviously not suited for replacing a single lost tooth. Well, ferrets teeth are very close to humans, so it working for them is already highly suggestive of it working for humans. Then, the antibodies being human ones, and that they even work in mice that are very very different teeth-wise from humans, is enough to warrant trying in humans. This isn't considering the safety (no predicted collateral damage; the antibodies target USAG-1 which has purposes beyond teeth growth inhibition), but yeah. Also see https://www.popularmechanics.com/science/health/a44786433/humans-have-third-set-teeth/ https://www.popularmechanics.com/science/health/a44786433/hu... ....
- mikeInAlaska 3y ago> 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 3y ago> 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 3y agoA 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.
- dekhn 3y agoThe cost of drugs like these is nontrivial, but much of that is dedicated to ensuring that what gets produced and delivered is actually what you wanted it to be. That is, you can make low quality mabs in a garage if you really knew what you were doing, but producing enough to sell without having patients dying of bacterial infections can't be done in a garage. Quality control combined with experienced production folks is critical.
- vikramkr 3y agoThe cell therapies are really expensive and struggling with manufacturing costs, mabs like these are priced what they are because of market forces.
- Terr_ 3y agoAs 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
- wizzwizz4 3y agoWe're already getting this particular dystopia with computer vision systems. The systems aren't particularly good, but that doesn't entirely matter to the people setting them off: their target lists aren't particularly well-curated either. We're a few hundred years past the point where technology is ever the bottleneck when it comes to making people dead. Extract from Self-Driving Issues by Randall Munroe. https://xkcd.com/1958 https://xkcd.com/1958 > "I guess it's just that most people aren't murderers?" "Oh, right. I always forget." "An underappreciated component of our road safety system."
- atombender 3y agoIsn't that paragraph describing some kind of homing bomb that's searching for the target ("pheromones and the color of his hair")? Does Gibson have any examples of what you describe, targeted molecules?
- dekhn 3y agoI 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 3y agoFlipping 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 3y agoThat'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 3y agoI think most people would prefer a study with more participants, but you can’t jump to a large human trial right away
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- Kalanos 3y agoIt'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 3y agoUsing 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/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5576142/
- deleted 3y ago[deleted]
- Kalanos 3y agothanks. yeah i dunno then First-line nivolumab metastatic colorectal w MMR: https://pubmed.ncbi.nlm.nih.gov/34637336/ https://pubmed.ncbi.nlm.nih.gov/34637336/ first-line keytruda metastatic colorectal w MMR: https://www.nejm.org/doi/full/10.1056/NEJMoa2017699 https://www.nejm.org/doi/full/10.1056/NEJMoa2017699
- tyingq 3y agoI'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 3y agoThey are https://en.m.wikipedia.org/wiki/PD-1_and_PD-L1_inhibitors https://en.m.wikipedia.org/wiki/PD-1_and_PD-L1_inhibitors The hint is the -mab naming.
- vikramkr 3y agoFor 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-drugs/fda-grants-regular-approval-dostarlimab-gxly-dmmr-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 3y agoSuccess with targeted therapy also hopefully paves the way towards the understanding we need for generalized solutions.
- tomaskafka 3y agoI don't think so - there is no 'general cancer', there's a lot of cancers ...
- vikramkr 3y agoThe better way of thinking about it is that this progress is allowing us to shift away from the idea of 'general' cancer or identifying cancer by tissue of origin to instead start identifying it by more useful and actionable features. So instead of talking about pancreatic cancer or colon cancer, with PD-1 inhibitors like keytruda we instead have an approval for any solid tumor that's mismatch repair deficient, something we can test for and that relates to the efficacy of a specific drug.
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- methodical 3y agoOriginal HN post on this same subject from 2022: https://news.ycombinator.com/item?id=31630679 https://news.ycombinator.com/item?id=31630679
- dang 3y agoThanks! Macroexpanded: A cancer trial’s unexpected result: Remission in every patient - https://news.ycombinator.com/item?id=31630679 https://news.ycombinator.com/item?id=31630679 - June 2022 (232 comments)
- aurizon 3y agoAre 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 https://www.youtube.com/watch?v=W2gABYTmXos
- methodical 3y agoI 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.
- hentrep 3y agoThis 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-waterfall-plot-achieved-with-neoadjuvant-immunotherapy-in-dmmr-colon-cancer/ https://ascopost.com/issues/october-25-2022/unprecedented-wa... [1] https://www.nyp.org/advances/article/gastroenterology/ongoing-research-shows-promising-results-for-neoadjuvant-treatment-for-colorectal-cancer https://www.nyp.org/advances/article/gastroenterology/ongoin...
- semi-extrinsic 3y agoFrom 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 3y agoReally 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 3y ago* in a 5-10% subset, of a subset, of a subset of cancers.
- hentrep 3y agoAt 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 3y agoIt’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.
- vikramkr 3y agoYep that's part of the advance here. Identifying what those subsets are. This drug went on to be approved for mismatch repair deficient endometrial cancers in 2023
- hinkley 3y agoWe are going to have to cure cancer about a thousand times before we have cured it.
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- ChrisArchitect 3y ago(2022)
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- jovial_cavalier 3y agoBuy Phillip Morris