4 ms·

Drug offers 'breakthrough' in treatment of asbestos-linked cancer

54 points by sandebert 3y ago

hello_computer 3y ago
[flagged]
- wozer 3y ago
  It may not be much, but it's an improvement that hasn't been seen for this type of cancer in a long time. But the headline is indeed quite misleading.
  - hello_computer 3y ago
    The average difference between chemo and no chemo at all is similarly underwhelming. Read just about any "when doctors die" piece, and it's clear that they rarely eat their own cooking, and with good reason. Given the choice between "death sentence" and "death sentence, with extra pain and suffering, and a fat bill for the family at the end", I think it's an easy choice.
    - magicalhippo 3y ago
      My dad's cancer spread to the lungs so radiation was off, and his kind didn't respond well to any chemo at the time. He then got pneumonia and the docs told us he'd likely have many months left once the pneumonia was treated, but he would most likely have to stay at the hospital until the end. He decided to ask them to stop the oxygen supply, and passed away peacefully the following day. It hit hard since it came earlier than expected, but I'm very grateful he was allowed to make that choice. I hope I get to make my own choice if the time comes.
    - peterfirefly 3y ago
      Depends very much on the cancer.
      - hello_computer 3y ago
        There may be some combination of cancer and treatment where progress has been made, but the aggregates are unimpressive, and if oncology were operating in the light, we'd have more numbers and classifications, and fewer glossy brochures filled with vague bulleted lists. I'd have odds instead of marketing adjectives.
- bgribble 3y ago
  > and quadrupled the survival at 36 months compared to placebo-chemotherapy There are lots of ways to slice the data. I think the one I quote is probably what got the researchers so excited. The problem is that the 36-month survival is pretty low, so even quadrupling it only increases the average survival time by the 1.6 months or whatever. Mesothelioma is one of the worst. My mom died of it at age 53, which is way too young.
  - hello_computer 3y ago
    When the heart-strings aren't being tugged, most people aren't totally stupid, and can understand basic statistics and probability distributions well enough, but those things are never given freely to the public when it comes to oncology. I can get a bell curve on different brands of hard drives or fuel injectors easily enough, but on a costly intervention that leads to much "collateral damage", that information is all behind a paywall in literal Greek. This is not an "oopsie". This is intentional.
- tasty_freeze 3y ago
  You are looking at it from the point of view of population statistics. But from the point of view of someone having only six months left to live, the extra 1.6 months is fantastic. (Yes, I know not everyone gets an extra 1.6 months, there is a distribution of outcomes averaging 1.6 months). The new treatment doesn't lower the quality of life for the patient, so this is a clear win. Cynical takes are a dime a dozen; improvements in outcome for this type of cancer is apparently rare. Guess which has more value.
  - hello_computer 3y ago
    It isn't a cynical take. It is the experience of seeing several family members take the chemo, suffer, then die shortly thereafter. If it hits me, I intend to do like Christopher Lasch did--take some pain-killers and go out with some bit of my dignity left intact. I read so many oncology papers in those days, and was thoroughly scandalized by them. Think of all the broad-spectrum bullshit there is in the software space, the financial space, the political space... but! doctors and researchers would never stoop so low?
- mschuster91 3y ago
  > 1.6 whole months! Of additional life on chemo! Will the miracles ever cease? /s Thing is, as a species we got a lot of the old killers tackled that held back human lifetime expectancy rates for milennia - illnesses that used to decimate or even wipe out entire populations got stopped by vaccines, antibiotics and sanitation measures, workplace injuries by OSHA and friends as well as automation, transportation of all kind by (very) strict regulations, drug consumption-associated diseases (cancer, liver failure) by taxes and banning ads. Or basically, we've long since flown by the 80% pareto mark of stuff that killed people before they reached retirement. Now, we have to deal with the hard stuff, that only shows up since people live long enough to experience it... cancers of all kind, the various forms of dementia (and these are nasty, I'd wager even worse than cancer!), retinal degradation, or bones getting brittle - many old but fit people tend to make a serious downturn after breaking a hip or whatnot from an unlucky fall and never recover from that. And unfortunately, that takes time, and progress only comes in very slow increment.
  - hello_computer 3y ago
    Anyone who is familiar with the numbers knows that "sanitation measures" were more effective than all of the other interventions you listed combined. But I didn't criticize sanitation, or vaccines, or any of the other things mentioned. I criticized chemotherapy. If you're excited about the prospect of zeroing-out the estate and suffering for an extra month or two to be a martyr for science, that is your business. When I read articles like this poorly disguised pharma PR piece, all that comes to my mind is, "Don't piss on my head and tell me it's raining." It is that bad.
    - mschuster91 3y ago
      Thing is, on the way to eventually make cancer a treatable disease we will have to endure a few decades worth of extremely small steps. Maybe less, if BioNTech's mRNA bet actually goes through, but that's far from a given.
      - hello_computer 3y ago
Metacelsus 3y ago
It's interesting how this drug works: by depleting arginine. Apparently mesothelioma cells lose the ability to make arginine. I wonder if a low-arginine diet would enhance the effect.
- hammock 3y ago
  Your body usually synthesizes all the arginine it needs, independent of dietary arginine
- xkcd-sucks 3y ago
  ultimately whether it works or not is up to a pretty complex network of kinetics, but low-arginine diet doesn't seem too plausible because it can be shuttled around between cells to some degree via plasma membrane transporters, produced to some degree from proteolysis etc. (https://www.sciencedirect.com/science/article/pii/S002231662303122X https://www.sciencedirect.com/science/article/pii/S002231662... etc) the approach, which is actually kind of nuts, supports this assumption: pegargiminase depletes by destroying arginine directly; it is fundamentally a super efficient arginine oxidizer coated in lube, more or less so it's like in principle most of your cells are making arginine and to some degree puking it out, this drug is chewing up all the free arginine floating around, the cells that can synthesize it are cool but the cells that can't synthesize it starve
hello_computer 3y ago
https://watermark.silverchair.com/jamaoncology_szlosarek_2024_oi_230088_1707156240.86267.pdf https://watermark.silverchair.com/jamaoncology_szlosarek_202... Prof Szlosarek reported grants from Barts Cancer Institute and Polaris Group and personal fees from Nestle Health Science (advisory board) during the conduct of the study. Dr Creelan reported grants from Iovance Biotherapeutics and SU2C/AACR; personal fees from Achilles Therapeutics, AstraZeneca, Regeneron, Hoffmann-La Roche, MJH Life Sciences, and ER Squibb LLC; and nonfinancial support from BMS and Clinigen outside the submitted work. Dr Taylor reported personal fees from AstraZeneca (speakers fees) outside the submitted work. Dr Grosso reported personal fees (advisory role) from MSD, BMS, Novartis, Novocure, and PharmaMar outside the submitted work. Dr Cortinovis reported personal fees (scientific adviser) from AstraZeneca, MSD, BMS, Roche, Sanofi Genzyme, Novartis, Amgen, and Seagen outside the submitted work. Dr Gilligan reported personal fees from AstraZeneca and Takeda outside the submitted work. Dr Kindler reported other from Polaris (payment to institution to support the clinical trial) during the conduct of the study; personal fees from AstraZeneca, Deciphera, Sanofi, Opna, Tempus, and Bluestar Genomics outside the submitted work. Dr Papadatos-Pastos reported personal fees from Takeda, MSD, Merck, AstraZeneca, Pfizer, and Amgen and travel support from Merck outside the submitted work. Dr Mansfield reported grants from Polaris Pharmaceuticals, Inc (payments to Mayo Clinic for conduct of clinical trial) during the conduct of the study; honoraria to Mayo Clinic from Sanofi Genzyme, Gilead, AbbVie, Immunocore, Roche, BeiGene, Janssen, and Bristol Myers Squibb Company, and serving on the board of directors (nonremunerated) for Mesothelioma Applied Research Foundation and Friends of Patan Hospital outside the submitted work. Dr Tsao reported personal fees from Ariad, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, EMD Serono, Genentech, GSK, Merck, Novartis, Pfizer, Roche, Seattle Genetics, Gilead Sciences, Inc, and Summit Therapeutics outside the submitted work. Dr Nowak reported nonfinancial support from Douglas Pharmaceuticals and AstraZeneca outside the submitted work. Dr Bomalaski reported a patent for Polaris Pharmaceuticals licensed to Polaris. Dr Zauderer reported grants from Polaris to MSK during the conduct of the study; grants to MSK from MedImmune, GSK, Epizyme, Sellas Life Sciences, BMS, Takeda, Curis, and Atara and personal fees from Curis, Ikena, Takeda, GSK, Novocure; and personal fees and CME content from PER, Medscape, and Research to Practice outside the submitted work; and serving as Chair, Board of Directors, for Mesothelioma Applied Research Foundation (uncompensated). Dr Fennell reported grants from Astex Therapeutics, Bayer Oncology, Boehringer Ingelheim, BMS, Bergen Bio, Roche Oncology, and GSK; personal fees from AstraZeneca; and nonfinancial support from Clovis Oncology, Eli Lilly, and MSD outside the submitted work. No other disclosures were reported.

54 points by sandebert 3y ago

hello_computer 3y ago

[flagged]

wozer 3y ago
It may not be much, but it's an improvement that hasn't been seen for this type of cancer in a long time. But the headline is indeed quite misleading.
- hello_computer 3y ago
  The average difference between chemo and no chemo at all is similarly underwhelming. Read just about any "when doctors die" piece, and it's clear that they rarely eat their own cooking, and with good reason. Given the choice between "death sentence" and "death sentence, with extra pain and suffering, and a fat bill for the family at the end", I think it's an easy choice.
  - magicalhippo 3y ago
    My dad's cancer spread to the lungs so radiation was off, and his kind didn't respond well to any chemo at the time. He then got pneumonia and the docs told us he'd likely have many months left once the pneumonia was treated, but he would most likely have to stay at the hospital until the end. He decided to ask them to stop the oxygen supply, and passed away peacefully the following day. It hit hard since it came earlier than expected, but I'm very grateful he was allowed to make that choice. I hope I get to make my own choice if the time comes.
  - peterfirefly 3y ago
    Depends very much on the cancer.
    - hello_computer 3y ago
      There may be some combination of cancer and treatment where progress has been made, but the aggregates are unimpressive, and if oncology were operating in the light, we'd have more numbers and classifications, and fewer glossy brochures filled with vague bulleted lists. I'd have odds instead of marketing adjectives.
bgribble 3y ago
> and quadrupled the survival at 36 months compared to placebo-chemotherapy There are lots of ways to slice the data. I think the one I quote is probably what got the researchers so excited. The problem is that the 36-month survival is pretty low, so even quadrupling it only increases the average survival time by the 1.6 months or whatever. Mesothelioma is one of the worst. My mom died of it at age 53, which is way too young.
- hello_computer 3y ago
  When the heart-strings aren't being tugged, most people aren't totally stupid, and can understand basic statistics and probability distributions well enough, but those things are never given freely to the public when it comes to oncology. I can get a bell curve on different brands of hard drives or fuel injectors easily enough, but on a costly intervention that leads to much "collateral damage", that information is all behind a paywall in literal Greek. This is not an "oopsie". This is intentional.
tasty_freeze 3y ago
You are looking at it from the point of view of population statistics. But from the point of view of someone having only six months left to live, the extra 1.6 months is fantastic. (Yes, I know not everyone gets an extra 1.6 months, there is a distribution of outcomes averaging 1.6 months). The new treatment doesn't lower the quality of life for the patient, so this is a clear win. Cynical takes are a dime a dozen; improvements in outcome for this type of cancer is apparently rare. Guess which has more value.
- hello_computer 3y ago
  It isn't a cynical take. It is the experience of seeing several family members take the chemo, suffer, then die shortly thereafter. If it hits me, I intend to do like Christopher Lasch did--take some pain-killers and go out with some bit of my dignity left intact. I read so many oncology papers in those days, and was thoroughly scandalized by them. Think of all the broad-spectrum bullshit there is in the software space, the financial space, the political space... but! doctors and researchers would never stoop so low?
mschuster91 3y ago
> 1.6 whole months! Of additional life on chemo! Will the miracles ever cease? /s Thing is, as a species we got a lot of the old killers tackled that held back human lifetime expectancy rates for milennia - illnesses that used to decimate or even wipe out entire populations got stopped by vaccines, antibiotics and sanitation measures, workplace injuries by OSHA and friends as well as automation, transportation of all kind by (very) strict regulations, drug consumption-associated diseases (cancer, liver failure) by taxes and banning ads. Or basically, we've long since flown by the 80% pareto mark of stuff that killed people before they reached retirement. Now, we have to deal with the hard stuff, that only shows up since people live long enough to experience it... cancers of all kind, the various forms of dementia (and these are nasty, I'd wager even worse than cancer!), retinal degradation, or bones getting brittle - many old but fit people tend to make a serious downturn after breaking a hip or whatnot from an unlucky fall and never recover from that. And unfortunately, that takes time, and progress only comes in very slow increment.
- hello_computer 3y ago
  Anyone who is familiar with the numbers knows that "sanitation measures" were more effective than all of the other interventions you listed combined. But I didn't criticize sanitation, or vaccines, or any of the other things mentioned. I criticized chemotherapy. If you're excited about the prospect of zeroing-out the estate and suffering for an extra month or two to be a martyr for science, that is your business. When I read articles like this poorly disguised pharma PR piece, all that comes to my mind is, "Don't piss on my head and tell me it's raining." It is that bad.
  - mschuster91 3y ago
    Thing is, on the way to eventually make cancer a treatable disease we will have to endure a few decades worth of extremely small steps. Maybe less, if BioNTech's mRNA bet actually goes through, but that's far from a given.
    - hello_computer 3y ago

Metacelsus 3y ago

It's interesting how this drug works: by depleting arginine. Apparently mesothelioma cells lose the ability to make arginine. I wonder if a low-arginine diet would enhance the effect.

hammock 3y ago
Your body usually synthesizes all the arginine it needs, independent of dietary arginine
xkcd-sucks 3y ago
ultimately whether it works or not is up to a pretty complex network of kinetics, but low-arginine diet doesn't seem too plausible because it can be shuttled around between cells to some degree via plasma membrane transporters, produced to some degree from proteolysis etc. (https://www.sciencedirect.com/science/article/pii/S002231662303122X https://www.sciencedirect.com/science/article/pii/S002231662... etc) the approach, which is actually kind of nuts, supports this assumption: pegargiminase depletes by destroying arginine directly; it is fundamentally a super efficient arginine oxidizer coated in lube, more or less so it's like in principle most of your cells are making arginine and to some degree puking it out, this drug is chewing up all the free arginine floating around, the cells that can synthesize it are cool but the cells that can't synthesize it starve

hello_computer 3y ago

https://watermark.silverchair.com/jamaoncology_szlosarek_2024_oi_230088_1707156240.86267.pdf https://watermark.silverchair.com/jamaoncology_szlosarek_202... Prof Szlosarek reported grants from Barts Cancer Institute and Polaris Group and personal fees from Nestle Health Science (advisory board) during the conduct of the study. Dr Creelan reported grants from Iovance Biotherapeutics and SU2C/AACR; personal fees from Achilles Therapeutics, AstraZeneca, Regeneron, Hoffmann-La Roche, MJH Life Sciences, and ER Squibb LLC; and nonfinancial support from BMS and Clinigen outside the submitted work. Dr Taylor reported personal fees from AstraZeneca (speakers fees) outside the submitted work. Dr Grosso reported personal fees (advisory role) from MSD, BMS, Novartis, Novocure, and PharmaMar outside the submitted work. Dr Cortinovis reported personal fees (scientific adviser) from AstraZeneca, MSD, BMS, Roche, Sanofi Genzyme, Novartis, Amgen, and Seagen outside the submitted work. Dr Gilligan reported personal fees from AstraZeneca and Takeda outside the submitted work. Dr Kindler reported other from Polaris (payment to institution to support the clinical trial) during the conduct of the study; personal fees from AstraZeneca, Deciphera, Sanofi, Opna, Tempus, and Bluestar Genomics outside the submitted work. Dr Papadatos-Pastos reported personal fees from Takeda, MSD, Merck, AstraZeneca, Pfizer, and Amgen and travel support from Merck outside the submitted work. Dr Mansfield reported grants from Polaris Pharmaceuticals, Inc (payments to Mayo Clinic for conduct of clinical trial) during the conduct of the study; honoraria to Mayo Clinic from Sanofi Genzyme, Gilead, AbbVie, Immunocore, Roche, BeiGene, Janssen, and Bristol Myers Squibb Company, and serving on the board of directors (nonremunerated) for Mesothelioma Applied Research Foundation and Friends of Patan Hospital outside the submitted work. Dr Tsao reported personal fees from Ariad, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, EMD Serono, Genentech, GSK, Merck, Novartis, Pfizer, Roche, Seattle Genetics, Gilead Sciences, Inc, and Summit Therapeutics outside the submitted work. Dr Nowak reported nonfinancial support from Douglas Pharmaceuticals and AstraZeneca outside the submitted work. Dr Bomalaski reported a patent for Polaris Pharmaceuticals licensed to Polaris. Dr Zauderer reported grants from Polaris to MSK during the conduct of the study; grants to MSK from MedImmune, GSK, Epizyme, Sellas Life Sciences, BMS, Takeda, Curis, and Atara and personal fees from Curis, Ikena, Takeda, GSK, Novocure; and personal fees and CME content from PER, Medscape, and Research to Practice outside the submitted work; and serving as Chair, Board of Directors, for Mesothelioma Applied Research Foundation (uncompensated). Dr Fennell reported grants from Astex Therapeutics, Bayer Oncology, Boehringer Ingelheim, BMS, Bergen Bio, Roche Oncology, and GSK; personal fees from AstraZeneca; and nonfinancial support from Clovis Oncology, Eli Lilly, and MSD outside the submitted work. No other disclosures were reported.