My 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.
For 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.
That'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.
Probably a decade ago a friend of mine passed from Acute Lymphocytic Leukemia in his 20s. I'm not sure what the differences are between ALL and CLL (other than knowing the differences between acute and chronic in a more general sense of course) but glad to see they are making at least some progress.
the chronic form is often written off when first diagnosed as "it will never affect you" - it can take decades to cause bigger problems. Dad's 80 and it's been causing bigger problems for some years. It would be surprising if there aren't new treatments for the acute form you mention as well.
> 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. "
As 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.
But 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.
A 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?
> At the time of presentation, 18 patients were enrolled on trial.
> Results among the 14 patients with at least 6 months follow-up showed a complete response among all patients (95% CI, 74-100), with no evidence of tumor on biopsy, digital rectal exam, endoscopic visualization, fluorodeoxyglucose-PET or MRI. The other four patients are responding to treatment.
70% 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
Because (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.
I mean if they've already tried everything else and nothing on the horizon and I just heard 12 of 12 people with same cancer as me had gone into remission after treatment? I'd probably be more than happy to become #13
In the clinical trials I have been a part of the manufacturer pays for the drug and all related study costs. They even pay you a stipend for commuting, lunch, etc.
The name of the drug ends in "-mab" [0] indicating that the drug is based on monoclonal antibodies [1,2]. Those antibodies are tweaked to bind to cancer cells which makes the immune system attack the cancer cells.
IIRC, in this particular case the antibodies bind to immune cells. Immune Checkpoints are a mechanism that keeps the immune system from attacking the own body but in cancer it can also stop the immune system from destroying the cancer. The checkpoint inhibitor antibodies remove these restrictions and allow the immune cells to attack the cancer. (The price is that they also become free to attack other things they shouldn't; autoimmune inflamations are common side effects.)
Several varieties of T cells are very dangerous and like to murder other cells. In order to prevent them from going on a rampage, they have a switch called PD-1 that calms them down. This prevents various auto-immune diseases in healthy people.
Some varieties of cancer cells release a PD-1 ligand that turns off T cells when they get close to the cancer. So the cancer can "hide" from the immune system.
This monoclonal antibody blocks PD-1 on T cells, turning them into unstoppable murderers. The hope is that they preferentially murder the cancer cells. Wikipedia says that ~5% of patients get dangerous side effects from blocking T cell PD-1, probably because the unstoppable T cells attack healthy kidney or liver tissue. But for people with specific types of cancer, the hope is that turning the T cells loose will kill the cancer first.
That 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.
Cancer cells (and our own cells) express PDL1. Our immune cells touch PDL1 with their PD1 and if this connection works then the immune cell does not kill.
If the connection does not work (PDL1 or PD1 absent) the immune cell will kill the target cell.
Couldn'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.
This 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.
> 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.
My 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.
I 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.
This 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).
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.
> 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?
Something I saw in drug pricing conferences is that there is a push to price drugs according to how much personal and social benefit they provide and how much a person would be willing to pay to extend their life or resolve a condition. An extreme example for that model, if a drug allow a kid to survive and have a productive life it can be priced millions whereas a palliative drug could be much cheaper.
This has nothing to do with research and cost of development anymore (if it even ever did).
But so two patients in different financial circumstances would both pay basically as much as they are able for a life-saving treatment, arriving at very different amounts, right?
- that sounds a lot like ransom?
- I think if they adopt a policy of price-discrimination to the point of literally taking you for all (or most) of what you're worth (or projected to be worth), we should turn around and apply the same reasoning to corporate tax rates.
I met a researcher once who was doing what appeared to be groundbreaking research on cancer care. He had this beautiful, tear-jerker story about losing his wife that cast a rosy, altruistic hue on his research. When he was asked what the device would cost, he cheerily replied "whatever the market will bear." That's always stuck with me -- the problem with American healthcare is the American interpretation of capitalism. Dude was living off of government research grants.
This 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
The other thing you can do is setup a trust for yourself so that you're broke on paper long before the trust runs out of money. I don't know if it's ethical but it's legal.
spend a decade of your life to possibly save a few years later? If you are “investing” your time for someone else, perhaps you could just give them your time directly instead?
Chemotherapy for 3-4 months is around $200,000 - $400,000.
You will not see a price reduction, if it doesn't require chemotherapy or significantly reduces the number of rounds of chemotherapy, this drug will cost $150k+ for full treatment.
All of this assumes side effects are better than chemotherapy. Given chemotherapy care plans are some of the most arduous, it will be hard to be worse than chemo.
Price is only slightly related to production costs. It’s much more about all the work that goes into getting something like this from basic science to trials to approval (and all the other drugs that fail along the way).
In the current model, pharma only stays in business by recouping all of the during the patent protected period of any drug that makes it to market.
Generally drugs that cure a condition cost MORE than the pre-existing treatments while under patent protection with no viable competitors. There’s only one source and you’d rather cure the disease with a pill so you’ll pay more.
Market dynamics don’t come into play when there’s only one. If competitors appear or after patents expire it may get cheap, but the cost early on will have no relation at all to production costs.
That's *insane*. Here in Scotland each dose costs the NHS at most a couple of hundred quid, plus about that again to administer. None of that is paid by the patient.
Probably not. That's an average-to-low price for a monoclonal antibody in the US, and many people with chronic (non-cancer) conditions pay that price every few weeks to remain healthy under something like a health-as-a-subscription model.
Some 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.
Otherwise redo your napkin math and cursory search to answer, specifically, whether all these cancers disappearing within weeks of dostarlimab treatment could be a fluke. And do not compare this to "rectal cancer's rate of survival", which is irrelevant and a completely different set of (parametrized) statistics, and also do not compare it to the total number of "cancer studies", which was an arbitrary choice and yielded this meaningless conclusion. Even if this kind of analysis was useful, why did you compare against the number of cancer studies, rather than rectal cancer (1910), or dostarlimab (41), or studies with the same staging and genetic pathology? It's meaningless.
I don't believe you're qualified to tell anyone about the significance of this study, and much less dismiss it as a fluke.
The point of that napkin math is not to get an exact prediction, it's to get a order-of-magnitude estimate to see if this study is different from any other of the large amount of "promising drug cures X" articles that never actually turn out to work.
I concede that if a quick remission is extremely rare that does change the outcome, though I don't know how common that it.
Picking 'Total number of "cancer studies"' was not arbitrary. A similar article could have been crated for e.g. "promising drug cures breast cancer" so you need to take all of them into account. Actually probably every study conducted of all high-profile diseases that are likely to wind up on the HN frontpage - in a counterfactual universe we could be discussing a miracle Alzheimer drug or the like.
Pretty sure the base rate you'd want to compare against is either placebo given -> remission or simply spontaneous remission. It appears that spontaneous remission is really quite rare.
> [sponanteous remission of cancer] incidence is roughly one in every 60 000–100 000 cancer patients, but the true figure is unknown (2). Spontaneous regression of colon cancer seems to be particularly rare
If spontaneous remission is super rare it does change the conclusion, yeah.
(Tangentially I think your stats are a little messed up there - you calculated the expected number of people out of 43000 surviving, not the trials returning a false positive. Assuming 0.0016% that chance is astronomically small, so your argument is stronger.)
This 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.
And 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%.
There should be some kind of award for these kinds of "well actually" comments on HN that lack any kind of intuition for the domain.
Cartoon montage: "By my calculations..." followed by driving a car off a bridge.
Edit: as someone who works in cancer research, I can tell you that your prior for 18/18 locally advanced colorectal cancer patients achieve CRs without surgery should be ~0.
If 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?
Other commenters have done a fine job expressing why this napkin math is silly and perhaps in isolated cases this is a good thing, OP probably learned something here
But in aggregate these sorts of comments are annoying as hell on every medical article posted to HN. Now you have to hope a sufficient mass of well-informed commenters is here to rebut them. In the best-case, these comments are simply misguided, but in the worst case it becomes a watering hole for all the antivaxxers and conspiracy theorists on this site to gather
If i put a single coin to the vending machine and get 7 cans instead of 0.98, i surely will try a few times more before reaching the conclusion my coins are magical beans.
Visibly medical research jump so quick to conclusion it's to the millions of news reader to swallow the clickbaits.
relatedly, 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.
I 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.
While 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.
Regret, 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.
The 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.
I'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.
Any 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.
There 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?
As 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.
Using 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.
Cancer 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.
I 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.
Along 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.
After 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.
-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.
There 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.
https://archive.is/eSDiX
My 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.
For 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.
FYI: your comment is a unique result for “metastatic solid-state tumors”[1], so much much less?
[1] https://www.google.co.nz/search?q=%22metastatic+solid-state+...
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What treatments in particular?
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That'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.
googled first to get the correct spellings and all that, been on hacker news a long time...
Similar story to the husband of my sister-in-law's sister (I think that's how you say it).
Metastatic Melanoma, had spread to his stomach. Got on the trial for Ipilimumab and is still here a decade and change later.
I’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.
That's amazing news. A close friend of mine recently died of this same leukemia (pretty sure.) I wish you and your family the best of luck.
Probably a decade ago a friend of mine passed from Acute Lymphocytic Leukemia in his 20s. I'm not sure what the differences are between ALL and CLL (other than knowing the differences between acute and chronic in a more general sense of course) but glad to see they are making at least some progress.
the chronic form is often written off when first diagnosed as "it will never affect you" - it can take decades to cause bigger problems. Dad's 80 and it's been causing bigger problems for some years. It would be surprising if there aren't new treatments for the acute form you mention as well.
Curious about the drug for non-hodgkins lymphoma, may have helped a friend who passed last year. Too late on one hand, but promising for future folks.
Sorry to hear about your dad but I'm happy he's doing better.
> 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
As 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.
But 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.
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A 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?
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Is this the same study?
https://www.healio.com/news/hematology-oncology/20220605/dos...
> At the time of presentation, 18 patients were enrolled on trial.
> Results among the 14 patients with at least 6 months follow-up showed a complete response among all patients (95% CI, 74-100), with no evidence of tumor on biopsy, digital rectal exam, endoscopic visualization, fluorodeoxyglucose-PET or MRI. The other four patients are responding to treatment.
This 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.
70% 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
[1] https://www.parexel.com/application/files_previous/5014/7274...
Because (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.
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After Phase 2, the drug has been proven safe.
In a sane and humane system, sick people would then be allowed to try it.
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I mean if they've already tried everything else and nothing on the horizon and I just heard 12 of 12 people with same cancer as me had gone into remission after treatment? I'd probably be more than happy to become #13
In the clinical trials I have been a part of the manufacturer pays for the drug and all related study costs. They even pay you a stipend for commuting, lunch, etc.
Fascinating, 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?
The name of the drug ends in "-mab" [0] indicating that the drug is based on monoclonal antibodies [1,2]. Those antibodies are tweaked to bind to cancer cells which makes the immune system attack the cancer cells.
[0] https://en.wikipedia.org/wiki/Drug_nomenclature#List_of_stem...
[1] https://en.wikipedia.org/wiki/Monoclonal_antibody
[2] https://en.wikipedia.org/wiki/Monoclonal_antibody_therapy
IIRC, in this particular case the antibodies bind to immune cells. Immune Checkpoints are a mechanism that keeps the immune system from attacking the own body but in cancer it can also stop the immune system from destroying the cancer. The checkpoint inhibitor antibodies remove these restrictions and allow the immune cells to attack the cancer. (The price is that they also become free to attack other things they shouldn't; autoimmune inflamations are common side effects.)
https://en.wikipedia.org/wiki/Checkpoint_inhibitor
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Several varieties of T cells are very dangerous and like to murder other cells. In order to prevent them from going on a rampage, they have a switch called PD-1 that calms them down. This prevents various auto-immune diseases in healthy people.
Some varieties of cancer cells release a PD-1 ligand that turns off T cells when they get close to the cancer. So the cancer can "hide" from the immune system.
This monoclonal antibody blocks PD-1 on T cells, turning them into unstoppable murderers. The hope is that they preferentially murder the cancer cells. Wikipedia says that ~5% of patients get dangerous side effects from blocking T cell PD-1, probably because the unstoppable T cells attack healthy kidney or liver tissue. But for people with specific types of cancer, the hope is that turning the T cells loose will kill the cancer first.
That 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.
Cancer 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.
It's an antibody.
https://en.m.wikipedia.org/wiki/Dostarlimab
https://en.wikipedia.org/wiki/Pembrolizumab
There are two types PD1 and PDL1 inhibitors.
Cancer cells (and our own cells) express PDL1. Our immune cells touch PDL1 with their PD1 and if this connection works then the immune cell does not kill.
If the connection does not work (PDL1 or PD1 absent) the immune cell will kill the target cell.
These antibodies either block PDL1 or PD1.
Couldn'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.
It’s not a small molecule, it’s a biologic (antibody). It was designed specifically to do what it does, and not discovered by chance.
This 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.
The 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.
> 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.
My 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.
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Maintaining well established medical procedures is much more important than some bio-robots dying.
I 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.
This 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-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.
> 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?
Something I saw in drug pricing conferences is that there is a push to price drugs according to how much personal and social benefit they provide and how much a person would be willing to pay to extend their life or resolve a condition. An extreme example for that model, if a drug allow a kid to survive and have a productive life it can be priced millions whereas a palliative drug could be much cheaper.
This has nothing to do with research and cost of development anymore (if it even ever did).
But so two patients in different financial circumstances would both pay basically as much as they are able for a life-saving treatment, arriving at very different amounts, right?
- that sounds a lot like ransom?
- I think if they adopt a policy of price-discrimination to the point of literally taking you for all (or most) of what you're worth (or projected to be worth), we should turn around and apply the same reasoning to corporate tax rates.
I met a researcher once who was doing what appeared to be groundbreaking research on cancer care. He had this beautiful, tear-jerker story about losing his wife that cast a rosy, altruistic hue on his research. When he was asked what the device would cost, he cheerily replied "whatever the market will bear." That's always stuck with me -- the problem with American healthcare is the American interpretation of capitalism. Dude was living off of government research grants.
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This 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
The other thing you can do is setup a trust for yourself so that you're broke on paper long before the trust runs out of money. I don't know if it's ethical but it's legal.
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spend a decade of your life to possibly save a few years later? If you are “investing” your time for someone else, perhaps you could just give them your time directly instead?
Is that the real price of a nursing home in the US? Who can afford that?
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Pay lots of money to spend more of your life dying
If you need a heart transplant, are you planning to self-pay that?
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No, the prices for drugs don't follow the same fundamentals that a normal economic market does.
If you want to learn more about pricing in healthcare the "Pricing, Value, and Ethics" lectures for this course is really interesting.
https://openlearninglibrary.mit.edu/courses/course-v1:MITx+1...
Could you explain that a bit? How does that interact with this?
https://www.fda.gov/about-fda/center-drug-evaluation-and-res...
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Chemotherapy for 3-4 months is around $200,000 - $400,000.
You will not see a price reduction, if it doesn't require chemotherapy or significantly reduces the number of rounds of chemotherapy, this drug will cost $150k+ for full treatment.
All of this assumes side effects are better than chemotherapy. Given chemotherapy care plans are some of the most arduous, it will be hard to be worse than chemo.
> Chemotherapy for 3-4 months is around $200,000 - $400,000.
Is that the american price or the "other developed countries" price?
Price is only slightly related to production costs. It’s much more about all the work that goes into getting something like this from basic science to trials to approval (and all the other drugs that fail along the way).
In the current model, pharma only stays in business by recouping all of the during the patent protected period of any drug that makes it to market.
Generally drugs that cure a condition cost MORE than the pre-existing treatments while under patent protection with no viable competitors. There’s only one source and you’d rather cure the disease with a pill so you’ll pay more.
Market dynamics don’t come into play when there’s only one. If competitors appear or after patents expire it may get cheap, but the cost early on will have no relation at all to production costs.
It's cheaper than other chemos..my mom has breast cancer and her chemo according to insurance cost 65k per infusion every 3 weeks.
That's *insane*. Here in Scotland each dose costs the NHS at most a couple of hundred quid, plus about that again to administer. None of that is paid by the patient.
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I would actually expect the opposite. If the drug is approved then the price would go up several times.
Probably not. That's an average-to-low price for a monoclonal antibody in the US, and many people with chronic (non-cancer) conditions pay that price every few weeks to remain healthy under something like a health-as-a-subscription model.
This price won't drop, it isn't common enough and still in clinical trials.
Some 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.
This analysis is mindless and inappropriate. If you care about this at all do yourself a favor and just read the study.
https://www.nejm.org/doi/full/10.1056/NEJMoa2201445
Otherwise redo your napkin math and cursory search to answer, specifically, whether all these cancers disappearing within weeks of dostarlimab treatment could be a fluke. And do not compare this to "rectal cancer's rate of survival", which is irrelevant and a completely different set of (parametrized) statistics, and also do not compare it to the total number of "cancer studies", which was an arbitrary choice and yielded this meaningless conclusion. Even if this kind of analysis was useful, why did you compare against the number of cancer studies, rather than rectal cancer (1910), or dostarlimab (41), or studies with the same staging and genetic pathology? It's meaningless.
I don't believe you're qualified to tell anyone about the significance of this study, and much less dismiss it as a fluke.
I bet he’s good at programming though.
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The point of that napkin math is not to get an exact prediction, it's to get a order-of-magnitude estimate to see if this study is different from any other of the large amount of "promising drug cures X" articles that never actually turn out to work.
I concede that if a quick remission is extremely rare that does change the outcome, though I don't know how common that it.
Picking 'Total number of "cancer studies"' was not arbitrary. A similar article could have been crated for e.g. "promising drug cures breast cancer" so you need to take all of them into account. Actually probably every study conducted of all high-profile diseases that are likely to wind up on the HN frontpage - in a counterfactual universe we could be discussing a miracle Alzheimer drug or the like.
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Pretty sure the base rate you'd want to compare against is either placebo given -> remission or simply spontaneous remission. It appears that spontaneous remission is really quite rare.
> [sponanteous remission of cancer] incidence is roughly one in every 60 000–100 000 cancer patients, but the true figure is unknown (2). Spontaneous regression of colon cancer seems to be particularly rare
https://academic.oup.com/jjco/article/45/1/111/888056
So using 0.0016% and 12 patients (which is what the paper the NYT actually links)
For a ~50% chance of seeing one trial with 12 patients have complete remission you'd expect to see ~43k trails.
(1 - 0.000016)^43000 = 0.502577
I wouldn't discount this study based off of those numbers.
If spontaneous remission is super rare it does change the conclusion, yeah.
(Tangentially I think your stats are a little messed up there - you calculated the expected number of people out of 43000 surviving, not the trials returning a false positive. Assuming 0.0016% that chance is astronomically small, so your argument is stronger.)
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This 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.
And 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%.
There should be some kind of award for these kinds of "well actually" comments on HN that lack any kind of intuition for the domain.
Cartoon montage: "By my calculations..." followed by driving a car off a bridge.
Edit: as someone who works in cancer research, I can tell you that your prior for 18/18 locally advanced colorectal cancer patients achieve CRs without surgery should be ~0.
They did not just survive. They had no traces of cancer. That chance is much much lower.
Your basic result stands, but "survival" and "remission" don't necessarily equate. But I agree with your basic point.
If 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?
Full remission without surgery?
This looks much more like tossing a dice 18 times and getting a 6 every single time!
With 1000 sided die perhaps
Other commenters have done a fine job expressing why this napkin math is silly and perhaps in isolated cases this is a good thing, OP probably learned something here
But in aggregate these sorts of comments are annoying as hell on every medical article posted to HN. Now you have to hope a sufficient mass of well-informed commenters is here to rebut them. In the best-case, these comments are simply misguided, but in the worst case it becomes a watering hole for all the antivaxxers and conspiracy theorists on this site to gather
If i put a single coin to the vending machine and get 7 cans instead of 0.98, i surely will try a few times more before reaching the conclusion my coins are magical beans. Visibly medical research jump so quick to conclusion it's to the millions of news reader to swallow the clickbaits.
7131 rectal cancer studies or just cancer studies in general?
relatedly, 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.
I 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.
While 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.
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Regret, 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.
The 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.
It’s true, but there’s no alternative. 99% of things don’t work.
generally speaking, “holy shit it worked?!!!” drowns out a lot. It’s not so much exhilaration as it is a kind of astonished joy.
The other reason is futility: the treatment has no benefit or any improvement is grossly outweighed by side effects.
I mean, treat everybody in the world with that condition at that point, right?
The treatment costs ~$100k over half a year.
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I'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.
Any 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.
I'll find out. How's your mum doing?
There 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?
As 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.
https://archive.ph/I4jqH
It 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.
Using 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.
Cancer 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.
I 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.
A 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.
Along 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.
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If you'd taken a moment to look 2 people have already posted archive links to get around the pay wall. Settle down.
From the FAQ <https://news.ycombinator.com/newsfaq.html>:
> It's ok to post stories from sites with paywalls that have workarounds.
> In comments, it's ok to ask how to read an article and to help other users do so. But please don't post complaints about paywalls.
Try the 'Bypass Paywalls Clean' web browser plug-in.
But - this doesn't sound like a monetizable drug? Just one treatment!!
I don't see this getting to market anytime soon.
After 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.
-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.
There 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.
This 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-app...
But, yeah, the FDA is all over the place.