15 ms·
A cancer trial’s unexpected result: Remission in every patient
- deleted 4y ago[deleted]
- greedo 4y agoAs a survivor of colorectal cancer, this is great news, even though the sample size is small and further studies are obviously needed. I'm hoping that by the time my children are at an age where they're at risk, treatments like this will be a well-established standard of care.
- grej 4y agohttps://archive.ph/I4jqH https://archive.ph/I4jqH
- hprotagonist 4y agorelatedly, the only good reason to stop a trial early is that it becomes unethical not to treat the control group because the effect size in the treatment group is so huge. And it does happen, sometimes.
- civilized 4y agoI sometimes wonder if the exhilaration of such a result comes with a twinge of regret that the result could not have been foreseen before the science reached it, and more people given the lifesaving treatment immediately. But that is the human condition, I guess. Scientific progress and learning brings regrets, often very momentous ones in retrospect.
- carapace 4y agoRegret, sure, but since we can't change the past that regret should motivate us to work harder to make the present and future better. We're a young species, and part of growing up is looking back with chagrin at how foolish we seem in the light of our new growth and learning.
- chrisbrandow 4y agoWhile I totally get what you mean, I’d guess for scientists, the answer is generally, “no”. Expected outcomes for trials like this are a whole lot less certain to the people doing the work, that than it seems on the outside, so i think it wouldn’t even occur to the scientists that the downside of “withholding” treatment from the tiny (relative to the population) control group comes close to the upside.
- civilized 4y agoYeah, it's just a wistful thing, and most of us laymen don't even experience the part where you want to know something but don't know it yet.
- aperson_hello 4y agoThe number of trials that don't work in humans when it worked in every pre-clinical trial up to that point is enough that it makes sense to be extra cautious.
- qgin 4y agoIt’s true, but there’s no alternative. 99% of things don’t work.
- hprotagonist 4y agogenerally speaking, “holy shit it worked?!!!” drowns out a lot. It’s not so much exhilaration as it is a kind of astonished joy.
- orblivion 4y agoI mean, treat everybody in the world with that condition at that point, right?
- thematrixturtle 4y agoThe treatment costs ~$100k over half a year.
- gumby 4y agoThe other reason is futility: the treatment has no benefit or any improvement is grossly outweighed by side effects.
- rubicon33 4y agoFascinating, this drug (molecule) somehow “unmasks” the cancer cells, allowing the body’s natural immune system to target and destroy them. How does a molecule do that!? Enters the blood stream, is absorbed by the cancer cell, and then…? Blocks some enzyme?
- vervez 4y agoCouldn't read the article but yea, if it's a small molecule, most likely it's inhibiting some protein specific to cancerous cells. In this case, it sounds like it's blocking some protein that blocks human cells' innate ability to produce antigens, which signal to T-cells that they are defective and need to be destroyed. Sometimes we understand the biology after we discover a treatment.
- epgui 4y agoIt’s not a small molecule, it’s a biologic (antibody). It was designed specifically to do what it does, and not discovered by chance.
- instagraham 4y agoThat is the function of checkpoint inhibitors, according to an explanation I got from a cancer researcher after asking a similar question. Essential, cancer cells convince the immune system not to attack them, so these inhibitors target the mechanisms by which they do so to get the immune system to take note of these cells. Hope someone more knowledgeable will correct me if I'm wrong.
- adamredwoods 4y agoCancer cells express proteins that communicate with lymphocytes (white blood cells) to block apoptosis (cell death). We can't target the cancer cells, so we tweak the lymphocytes to block PD-1 receptors, thus ignoring ALL cells that express a lot of PD-L! protein. This unfortunately includes healthy cells.
- ohazi 4y ago
- MontagFTB 4y ago> The medication was given every three weeks for six months and cost about $11,000 per dose. That’s an $88,000 treatment for the medication alone. Given the apparent success of the drug, is it expected for the price to drop as the volume of patients spike?
- georgeburdell 4y agoThis is why although I’ve almost got enough money to retire (~20x yearly expenses) but I’ll keep on working for another decade or two. All of these whiz-bang new treatments are going to be expensive. The most expensive medical procedure right now is a heart transplant at about $1M. Then there’s the $10k/mo for a nursing home
- ta988 4y agoIs that the real price of a nursing home in the US? Who can afford that?
- horsawlarway 4y agoYes - that's not unreasonable for a full time care facility for something like dementia or Alzheimer's in the US (it's below what we paid for my grandmothers). If you're lucky - they have long term care insurance, and that covers most of the expenses for approx 2 to 10 years (depending on how old the insurance is - it's getting harder to find long plans, and they're all getting significantly more expensive as it turns out more folks needed them). Otherwise... you spend everything, and then your kids pay. We split my grandmothers down the middle - my mom's had insurance, we covered my dad's.
- spywaregorilla 4y agoI'd rather just die. Throw a party. Tell my kids they're getting a ton of cash. Say good bye on happy terms. Vs. a miserable decay for everyone involved at huge expense. It's not worth it. Forget the money. The emotional toll is large and for whose benefit?
- SiempreViernes 4y agoUsing humans, N = 18. Quick search didn't give any estimate of the chance probability of all going into remission by unrelated reasons, but I imagine it's pretty high compared to the number of small cancer trials run around the world.
- dekhn 4y agoCancer rarely, if ever goes into remission on its own (rectal cancer, specifically). You would never see this happen randomly to everybody in a trial unless there was some external factor.
- LinuxBender 4y agoI don't have a link handy but I have read in the past some cases of trial participants being ejected from a trial because they started prolonged fasting and killed their cancer cells. I suppose that is in line with the external factor you mention.
- js4ever 4y agohttps://archive.is/eSDiX https://archive.is/eSDiX
- Aransentin 4y agoSome napkin math: Given rectal cancer's rate of survival of 67%, and the small size of the study (18 people), you should see similar results due to random chance every 1350th study. A cursory search on clinicaltrials.gov and I can find 7131 cancer studies started in 2021 alone. It's therefore not unreasonable for this one to be just a random fluke.
- rossdavidh 4y agoYour basic result stands, but "survival" and "remission" don't necessarily equate. But I agree with your basic point.
- yakak 4y agoIf I understand the article correctly they were excluding patients enrolled in chemo and radiation? If that's what they mean the survival rate wouldn't be 67% so this would imply a 1349 in 1350 chance the treatment is better than the average treatment?
- inglor_cz 4y agoThis napkin math ignores some very significant circumstances. People who suffer from rectal cancer usually undergo surgery to remove the primary tumor. But those trial patients weren't operated on, their treatment was non-invasive. How many rectal cancer sufferers who never undergo a surgery survive? I would bet that it is a lot less than 67 per cent.
- cowmoo728 4y agoAnd this was people with locally advanced rectal cancer. Typically this means the tumor has grown to a considerable size and is already causing symptoms severe enough for people to go to a specialist. I am not a doctor but my understanding is that a placebo in this case would have a 5 year survival rate that is pretty close to 0%.
- raindear 4y agoThey did not just survive. They had no traces of cancer. That chance is much much lower.
- pella 4y ago> It was a small trial, just 18 rectal cancer patients, just 12 "All 12 patients (100%; 95% confidence interval, 74 to 100) had a clinical complete response, with no evidence of tumor on magnetic resonance imaging, 18F-fluorodeoxyglucose–positron-emission tomography, endoscopic evaluation, digital rectal examination, or biopsy. " https://www.nejm.org/doi/full/10.1056/NEJMoa2201445 https://www.nejm.org/doi/full/10.1056/NEJMoa2201445
- abirch 4y agoAs with most experiments there's a control group (6 patients). The original statement of 18 participants is correct along with yours of 12 patient treatment group.
- dash2 4y agoBut then I guess it is slightly less surprising that all 12 people had remission, rather than all 18. (Or if all 18 had remission, then that's amazing but might not be to do with the drug.) Maybe it is still a great result, just slightly less significant.
- abirch 4y agoYou're correct. We'd expect to see more extreme outcomes with smaller sample sizes. The question is does this translate to more drugs when administered early which was the real reason for this study.
- satellite2 4y agoA placebo control group when there is an established standard of care? That sounds highly unethical. The above link to the abstract don't mention this and I don't have access to the full text paper. If you do can you clarify what the control arm received?
- abirch 4y agoI intentionally avoided using placebo group. The control cohort may not have had cancer at all _____________ The plan is to enroll six patients with MSI, regardless of their primary cancer diagnosis. This cohort will serve to generate hypothesis and initial data to plan a larger study. All analyses from this cohort will be exploratory https://clinicaltrials.gov/ct2/show/NCT04165772 https://clinicaltrials.gov/ct2/show/NCT04165772
- zzzeek 4y agoMy dad was fortunate enough to get into a trial at Sloan for Obinutuzumab for Chronic Lymphocytic Leukemia. At the moment, after 6 weeks of treatment, the percent of cancerous cells in his bone marrow has gone from 95% to 5%. The treatment was very intense as it overloads the kidneys on the first few treatments due to the dramatic amount of cells being flushed out. This is a cancer for which there was not much treatment previously other than extreme chemotherapy which still left little hope for complete remission. A family friend was also treated for Non-Hodgkins' lymphoma on another drug trial and she's now in full remission. my uninformed impression is that there's a lot of new cancer treatments happening now that can turn the tide for a lot of types of cancer.
- fnordpiglet 4y agoI’m glad to hear about the positive outcomes for your dad. I hope he beats the cancer. It’s an exciting time to be alive.
- abirch 4y agoThat's great for your dad. Thank you for also distinguishing between types of cancer and the nebulous term cancer, many people don't make the distinction.
- zzzeek 4y agogoogled first to get the correct spellings and all that, been on hacker news a long time...
- adamredwoods 4y agoFor leukemia, there are a lot of promising new treatments and clinical trials. For metastatic solid-state tumors, much less. We're still in the dark ages of cancer treatment.
- axpy906 4y agoWhat treatments in particular?
- xiphias2 4y agoThis experiment of treating cancer with checkpoint inhibitors before chemotherapy should be widened to all cancers where the CI is available and effective as soon as possible, as it can cure lots of lives. I'm worried that it will take many years until that happens.
- ImHereToVote 4y agoMaintaining well established medical procedures is much more important than some bio-robots dying.
- adamredwoods 4y agoThe treatment is not without side effects. It's still a general therapy (it blocks all lymphocyte PD-1 receptors), not a cancer-target one. Oncology is slow. It really is up to the patients to push the oncologist teams.
- bsder 4y ago> I'm worried that it will take many years until that happens. For good reason. If we detect cancers early, surgery and radiation are often very good nowadays--often allowing you to skip chemotherapy. And these are far less likely to kill the patient than a checkpoint inhibitor (which can overload your kidneys if it works or give you autoimmune diseases even if it doesn't). The problem is that there are a lot of cancers we don't detect early-lobular breast cancer, pancreatic cancer, etc. And for things like intestinal cancers radiation is particularly bad. These kinds of immune treatments are likely to get promoted first line treatments quickly if they really are this good--especially since they are likely to work on stage 4 metastatic cancers for which we don't have anything decent.
- xiphias2 4y agoMy ex girlfriend detected breast cancer early at age 28, but the doctors told her that she's ,,too young'' to have cancer. 1 year later on the checkup they said that it's too late (she has BRCA1 mutation). The last 10 years have been fighting with cancer, having about 10 operations on her, but the worst thing was chemotherapy (she said that she would rather die than go through it again, I think the dose had been too large for her probably as well, as she's 44kg). The cancer went away and came back multiple times, and it got so bad that we had to separate, but she's still my best friend (and I didn't find any other person to spend my life with). She's right now on an experimental checkpoint inhibitor (stage 4 metastatic since a year ago), and it probably gives her another few months, but every time I see her I think that she only has a year left in her life and get sometimes frustrated that the experiments are not optimized to get the more effective treatments in earlier stage.
- sonicggg 4y agoAfter reading it, my suspicion was confirmed. Yet another mab. Very powerful, but expensive to scale and synthesise. I guess poor people will have to just suck it up and die. We don't have the tech yet to make these cost effective. Big pharma loves this natural barrier of entry though. Also, don't expect this stuff to be available anytime soon. FDA process is pretty slow, and sometimes political. Maybe if it were effective against Sars-Cov-2, FDA would be willing again to rush it though the door. Still can't wrap my head around how stuff like Molnupiravir made the cut. They just don't have any shame.
- adamredwoods 4y agoThis is why there is a fast-track to accelerate break-through treatments, which dostarlimab utilized (but stalled thanks to covid): https://www.fda.gov/patients/learn-about-drug-and-device-approvals/fast-track-breakthrough-therapy-accelerated-approval-priority-review https://www.fda.gov/patients/learn-about-drug-and-device-app... But, yeah, the FDA is all over the place.
- GordonS 4y ago-mab drugs really are incredible. I actually take 2 different ones (erenumab and omalizumab), and the results surpassed all my expectations, especially after negative or lacklustre results from many "conventional" medications beforehand. But aye, they aren't cheap.
- inglor_cz 4y agoThere were times when aluminium was so expensive that the French emperor dined on an aluminium plate. His guests had to do with gold and silver. Several decades later, aluminium was an everyday material. I definitely hope that we can come with a cheap method of -mab production. I am almost sure we one day will.
- Gordonjcp 4y agoI'm not sure which immunotherapy drug my mother has been receiving, but after being diagnosed with lung cancer nearly two years ago - a tumour roughly the size of a tangerine right in the top corner of one lung, utterly inaccessible by surgery, in absolutely the wrong place to attempt radiotherapy - it's now gone, save for a little bit of scarring and fibrosis where it used to be. The treatment has left her tired and brain-foggy but that's pretty small potatoes to being a chemo zombie, which she absolutely did not want. Although she's in her early 80s she's otherwise in not too bad shape, so that probably helped. From here on out, it'll be scans every three months or so to make sure it hasn't come back, but her doctor says that if it does come back it'll grow so slowly and weakly that it's just not going to be worth bothering with. I expect you can imagine the look on Mum's doctor's face when we went in for the most recent scan results - it can't be often an oncologist gets to give someone the best news in the world.
- rjm226 4y agoAny idea what cancer she had and what treatment? My mom is currently battling stage 4 metastatic neuroendocrine primary lung cancer atypical carcinoid and being treated with Lutathera, a nuclear injection that targets the somatostatin receptor on the cancer cells and hopefully shrinks, slows, or kills them off. The treatment is 1 injection every 2 months over the course of 8 months. So 4 total injections. She has already been through 4 rounds of chemotherapy and targeted radiation. She has many tumors at this point but the largest sounded similar to your moms, upper left lung, the size of a golf ball. Partially collapsed her left lung. She's being treated at Sloan Kettering in NYC.
- Gordonjcp 4y agoI'll find out. How's your mum doing?
- BnRJ401E29F8Q3v 4y ago[flagged]
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- mmcnl 4y agoThere are many articles like this every year. I understand there's no silver bullet for curing cancer, but I am interested in the actual results of new treatments instead of the potential of new treatments, which seems to attract way more headlines. Is there an overview somewhere of new treatments over the years, and their effect? What is the progress we have made?
- epmaybe 4y agoI got to spend a couple of weeks as an internal medicine intern with a medical oncologist who incidentally worked at memorial sloan prior to coming to my university. You could tell how excited he was about the current state of cancer research and new treatments, especially with immunotherapy. Wonder if docs will start off-label treating earlier with immunotherapy. There's tons of immune checkpoint inhibitors meant for different types of cancers and mutations.
- genkiman 4y ago
- mchusma 4y agoThis brings up again the sorry state of medicine being "default banned". Should this treatment be banned for patients? Absolutely not. Is it a small, underpowered study that needs to be replicated? Absolutely. Could it warrant banning in the future? Sure. Should it be covered by insurance? Complicated. We need to unbundle these things.
- scoopertrooper 4y ago70% of Phase 2 trials fail and 50% of Phase 3 trials fail[1]. Why should the default to be to approve drugs in the early stage of human experimentation? Here are some interesting case studies of drugs graduating from Phase 2 trials only to fail Phase 3 trials on efficacy and safety grounds: https://www.fda.gov/media/102332/download https://www.fda.gov/media/102332/download [1] https://www.parexel.com/application/files_previous/5014/7274/5573/ACT_Article.pdf https://www.parexel.com/application/files_previous/5014/7274...
- rzz3 4y agoBecause (at least) for people with a high risk of dying, and operating under well-informed consent, that decision should be between patients and their doctors alone.
- photonic31 4y ago
- sumedh 4y ago> Because (at least) for people with a high risk of dying and who decides that? Can a drug company give "gifts" to doctor who then recommend the patient use that company's drugs when he/she is dying?
- hp48fan 4y agoBecause it would degenerate into pharmaceuticals selling false hope in exchange for lab rats that are too far along to be saved even if the drugs work. That being said I disagree with prescription pads. I should buy antibiotics for my kid without waiting four, five hours to be seen and processed
- verisimi 4y agoBut - this doesn't sound like a monetizable drug? Just one treatment!! I don't see this getting to market anytime soon.
- lawrenceyan 4y agoA healthy reminder that these articles are generally sponsored by the company developing the specific drug. Cancers will be mostly treatable within our lifetimes though (in many cases already are). All the pieces are there technology wise.
- Izkata 4y agoAlong similar lines, I remember reading about a drug/treatment about 15-20 years ago that had similarly extremely positive results, and nothing since. That one worked by reactivating mitochondria in the cancer cells so that they could trigger apoptosis and the cancer would kill itself.
- pazimzadeh 4y agoIt makes sense to me that immunotherapy should work better if attempted before chemotherapy, since chemo damages the immune system. The idea of trying immunotherapy if chemo fails seems completely backwards.
- sam537 4y agoThis is misleading. Yes, the response rate is extremely high but all of this patients shared a mutation or a group of mutations in mismatch repair proteins (they were all MMR deficient, or mismatch instability high). This effect is shared across many tumors with this feature not only rectal and the FDA approved a drug with the same exact mechanism in 2017 (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pembrolizumab-first-tissuesite-agnostic-indication https://www.fda.gov/drugs/resources-information-approved-dru...) If I had to guess this is a huge marketing plot to bring yet another extremely expensive drug to the market. What is happening is that different drugs (ie different companies) take the space of a specific tumor (Keytruda for lung, Opdivo for melanoma, Tecentriq for liveer cancer) and Dostarlimab is going to claim the rectal cancer space.