A cancer trial’s unexpected result: Remission in every patient • Hacker News Board

Re: A cancer trial’s unexpected result: Remission in every patient

#191

Post by sam537 » Mon, Jun 06, 2022, 2:56 AM UTC

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.

Re: A cancer trial’s unexpected result: Remission in every patient

#192

Post by sam537 » Mon, Jun 06, 2022, 2:59 AM UTC

rubicon33 wrote: post #7

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?

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.

Re: A cancer trial’s unexpected result: Remission in every patient

#193

Post by dodobirdlord » Mon, Jun 06, 2022, 3:23 AM UTC

pas wrote: post #189

weezin wrote: post #181

Earlier quoted context omitted.

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...

After you file for a drug patent it takes 3-4 years to get approved. You also have to run clinical trials of various sorts, which take years, and then you need widespread marketing campaigns to ensure that doctors are aware of the new treatment. A rough rule of thumb is that it takes about 10 years from the point of filing the patent before you can actually bring the drug to market.

Drug patents are good for 20 years from the filing date, so you have about 10 years to recoup all of your costs, recoup the necessary fraction of your amortized R&D expenses on drugs that didn't go anywhere, and hopefully turn some profit, before your patent expires and generic manufacturers undercut you.

The result is that cutting edge drugs are extremely expensive for the decade or so after they first become available while the patent holder uses their patent-provided monopoly to set prices at the maximum that insurance companies and government health providers will pay. Your link is discussing the period of time after the patent expires and generic manufacturers get into the game, but the drug being discussed here with its $88,000 treatment cost is still in the patent-protected cost-recouping stage, where it's not subject to normal market principles of supply and demand because the supply side is a temporary monopoly.

Re: A cancer trial’s unexpected result: Remission in every patient

#194

Post by turtledove » Mon, Jun 06, 2022, 3:26 AM UTC

brigandish wrote: post #170

goodpoint wrote: post #51

Earlier quoted context omitted.

> What should it cost instead? To patients? It should be free. To society? The initial research cost plus the bare manufacturing cost.

> To patients? It should be free. Someone has to pay. Who pays? > To society? The initial research cost plus the bare manufacturing cost. And we're back to a society which is poorer in terms of both health and wealth.

Ah yes, a society with low cost medicines and a healthy research investment - definitely a recipe for low wealth and health. /s

Re: A cancer trial’s unexpected result: Remission in every patient

#195

Post by [deleted] » Mon, Jun 06, 2022, 4:22 AM UTC

scoopertrooper wrote: post #160

BurningFrog wrote: post #156

Earlier quoted context omitted.

After Phase 2, the drug has been proven safe. In a sane and humane system, sick people would then be allowed to try it.

I just gave you a document containing 8 case studies where drugs were found to be not safe after having passed Phase 2 trials.

[deleted]

Re: A cancer trial’s unexpected result: Remission in every patient

#196

Post by rad88 » Mon, Jun 06, 2022, 5:14 AM UTC

Aransentin wrote: post #185

rad88 wrote: post #127

Earlier quoted context omitted.

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 irrel…

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"' wa…

No, you can't actually figure out whether a cancer therapy worked by counting the number of articles published in a given year. You're focused on this "zero-knowledge" approach because you are completely ignorant about this topic, not because it is actually a more powerful approach.

If you don't even know whether spontaneous remission is rare then you should not be offering an opinion about this. It's not even pertinent because these remissions were clearly not spontaneous, but it should alarm you to have spoken so recklessly about a disease which is essentially fatal. What you're saying amounts to "there's a good chance cancer just goes away on its own". Incidentally, this is also the least amount of math I've ever seen in a napkin math argument.

Re: A cancer trial’s unexpected result: Remission in every patient

#197

Post by bwb » Mon, Jun 06, 2022, 6:41 AM UTC

caddemon wrote: post #81

bwb wrote: post #64

Earlier quoted context omitted.

That is not true, look up medical outcome data. Most of europe is far ahead or even with the USA.

Unless you are looking at outcomes of only the top institutions it's not really what he was saying. The US has a bad system for the average person for sure, but that does not mean that the US doesn't have one of the best systems if you can afford the best care. If you have medical outcome data that disputes that specifically I'd be interested.

Why would you think the best hospitals in the USA outperform any other developed country's best hospitals? Especially when those countries already deliver better average results across the board. Why do you have this belief and what is it based on?

One example of cancer outcomes on a per country basis: https://worldpopulationreview.com/country-rankings/cancer-su...

Just google medical outcomes for any disease on a per country basis.

Do you really think the best hospitals in France or somehow worse than the best hospitals in the USA? Especially when the best hospitals in the USA still have the same fundamental problems as the rest of the American system?

Re: A cancer trial’s unexpected result: Remission in every patient

#198

Post by isitmadeofglass » Mon, Jun 06, 2022, 6:57 AM UTC

rzz3 wrote: post #149

scoopertrooper wrote: post #141

Earlier quoted context omitted.

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.

If we allowed any type of experimentation on dying patients as long as there was consent, dying patients would end up getting used as a Guineapigs by companies trying to get a lucky indication. It would certainly benefit the families left behind financially, but it would not be pretty. “Here’s a million bucks, please take these 40 drugs that will certainly kill you, but we’ll learn which one we should continue with”. And why even do toxicity studies or phase 1 and 2 trials? It’s cheaper to pay of poor people who are on the verge of dying and just pushing them over the edge.

The decision should be just because a patient and a doctor, because the consequences of such decisions are more far reaching than just those two. We have a well established framework for what a drug needs to prove before they can reasonable be allowed to be given to any human being, no matter their situation, and that barrier of entry is there for a multitude of good reasons. Discarding it just because a specific patient is at risk of dying or because you can get consent is not helping patients.

Re: A cancer trial’s unexpected result: Remission in every patient

#199

Post by brigandish » Mon, Jun 06, 2022, 8:16 AM UTC

turtledove wrote: post #194

brigandish wrote: post #170

Earlier quoted context omitted.

> To patients? It should be free. Someone has to pay. Who pays? > To society? The initial research cost plus the bare manufacturing cost. And we're back to a society which is poorer in terms of both health and wealth.

Ah yes, a society with low cost medicines and a healthy research investment - definitely a recipe for low wealth and health. /s

I also dream of utopia but when I wake up I have to supply the logic that fills in the gaps else it remains a dream.

If you remove the profit motive then investment falls, new medicines become less likely and lesser in number, and medicines remain higher in cost due to lack of pressure (competition from new drugs, competition from new entrants, new techniques etc).

Altruism, necessary as it is, does not fill that void alone, and it certainly won't be filled by hoping government makes everything "free".

Re: A cancer trial’s unexpected result: Remission in every patient

#200

Post by brigandish » Mon, Jun 06, 2022, 8:24 AM UTC

pmyteh wrote: post #71

brigandish wrote: post #52

Earlier quoted context omitted.

Please don't give insincere apologies, they're rhetorically weak and pairing insincerity with something that should be sincere isn't a good look. Which segues nicely to this pairing of public funding and private enterprise. No, if the drug wouldn't be sold for a profit then the incentive to make it wouldn't exist and the funds would not be applied for and the ironic pairing - if it is ironic, which I don't think it i…

I don't know about medical research, but that's exactly what the rest of us in universities do.

Academic research is valuable, as is the research done by commercial entities. They're really not comparable in their intent though, and that's a good thing.