8 ms·

Immunotherapy cancer drug hailed as 'game changer'

137 points by sjcsjc 10y ago

OrthoMetaPara 10y ago
Apparently, these tumors proliferate because they are able to trick killer T cells into not attacking them. The antibody, nivolumab, inhibits this signaling pathway so that the T-cells are capable of attacking the tumor. From: Gettinger SN, Horn L, Gandhi L, et al. Overall Survival and Long-Term Safety of Nivolumab (Anti–Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non–Small-Cell Lung Cancer. Journal of Clinical Oncology. 2015;33(18):2004-2012. doi:10.1200/JCO.2014.58.3708. Programmed death 1 (PD-1) is an immune checkpoint receptor expressed on activated T cells, which normally serves to dampen the immune response to protect against excessive inflammation and the development of autoimmunity. However, in the setting of malignancy, PD-1 signaling, driven primarily by adaptive expression of programmed death ligand 1 (PD-L1) within the tumor, inactivates primed T cells that recognize tumor-specific antigens, allowing tumor growth and metastasis. PD-1 pathway blockade with monoclonal antibodies offers a novel approach to restoring T cell–mediated antitumor immunity, with the potential for application across a broad population of patients with NSCLC. From the article: In a trial of more than 350 patients, published in the New England Journal of Medicine, 36% treated with the immunotherapy drug nivolumab were alive after one year compared with 17% who received chemotherapy. That seems like a small improvement rather than a "game changer."
- JoshTko 10y ago
  Doubling survival rates while having far less severe side effects along with proven effectiveness on multiple different types of cancer is definitely a major breakthrough. This is also based on human trails and not rats in a lab.
  - agumonkey 10y ago
    That sentence is such a pleasure to read.
  - danieltillett 10y ago
    I wish most cancers treatments were tested in rats in the lab - most of the time they only get tested in inbred mice which are a terrible model for human cancer.
- deleted 10y ago
  [deleted]
- ekianjo 10y ago
  > That seems like a small improvement rather than a "game changer." It shows you are not really aware of the state of Cancer drugs these days. Drugs that can make 20~30% patients live 3 months longer are usually considered pretty good, doubling the percentage of survival in ADVANCED cancer is certainly unheard of.
  - OrthoMetaPara 10y ago
    That's a pretty pathetic standard for "good" Chimeric Antigen Receptor therapy seems like more of a "game changer," given that it's a new therapeutic direction. This is just another monoclonal antibody.
    - apathy 10y ago
      Spoken like someone who hasn't been following the Kite trials... Also of note: just like good ol' mAbs, you need a target for CAR-T cells. And BiTEs, and BiKEs, and what have you. Also also of note: the approaches that took pediatric ALL and adult APL (among others) from 5-10% survival to 90-95% survival weren't single pronged. (Good thing, too; I've seen patients who seemed ideal for CAR-T die when their malignancy outran the engineered cells) The majority of progress in real-world outcomes has arisen from combination or sequential therapies, incrementally improved to decrease toxicity and maximize efficacy. Which is to say, incrementally advanced. Last: per the above, you can use the two together. If a tumor is actively suppressing T cells, it isn't going to dissolve from CAR-T cells without a fight. There are additional tactics useful for "priming" the immune system, but in the end I don't see a lot of solid tumors melting away in trials of CAR-T cells (feel free to correct me). Do take a look at the Kite trials and how they're structured. When you have to condition a patient with fludarabine to hit outcomes (at all) that's not a wonder drug. It's another tool in the toolbox. A necessary and useful tool, but a tool, not a magic wand.
      - apathy 10y ago
        Hey, just so I'm not a total hypocrite, it turns out that you can "turn off" PD-1 and PD-L1 response in CAR-T cells (at least in mouse models, https://www.jci.org/articles/view/83092 https://www.jci.org/articles/view/83092 ). In the end I stand by my contention that it's a tool and it needs to be used for the right jobs, but it's a very versatile tool. I work on immunosenescence and immune stimulation (the real thing) in oncology, and I happen to believe that we do many patients a disservice by nuking their immune systems with chemo and then relying on things like TKIs or BiTEs to pick up the mess. But it's also important to keep in mind that Gleevec alone didn't get rid of CML, and the way ALL and APL were managed up to 95% cure rates is by adding a little poison (As2O3, methotrexate, etc.) to the brew (asterisk) to finish things off. It's a delicate balance. I think it always will be. (asterisk: ok more like a metric fuckload of poisons for ALL. But the real trick is "resurrecting" the patient with leukovorin after folate starvation essentially kills them.) http://blogs.sciencemag.org/pipeline/archives/2016/07/08/car-t-deaths-cannot-be-good http://blogs.sciencemag.org/pipeline/archives/2016/07/08/car... Look up the SuperMAB saga for more cautionary tales. Plenty of people have died from chemo and immunosuppression too (nobody benefits from lungs full of aspergillus and a gut full of C. diff). If it were easy, somebody would have figured it out already :-)
- nsgi 10y ago
  Twice the number surviving one year without the side effects of chemotherapy seems like a pretty big improvement to me, although there are a lot of news articles prematurely hyping "cures for cancer" that will probably never see the light of day.
  - charlesism 10y ago
    Well, that's the problem with relative numbers. If my absolute chance of survival increases from 0.1% to 0.2%, I'll take a pass.
    - PakG1 10y ago
      Would you choose nothing? If not nothing, why wouldn't you choose the option with a slightly higher chance of success and fewer side effects?
      - charlesism 10y ago
        It depends on how well studied the treatment is. If it's been on the market for 70 years, I'd take the chance. Otherwise, why risk waking up one morning with a tail, or having my arm fall off ;)
        rangibaby 10y ago
        Because you are going to die pretty quickly either way if you have terminal cancer. At least if you try a new treatment you could theoretically help other people in the future live for longer, and other people who will get very, very rich. lol
        charlesism 10y ago
        If news like this brings people hope, I suppose I shouldn't complain too loudly.
        10y ago
- yaakov34 10y ago
  It's a very big improvement, relative to most cancer treatment advances, assuming it holds up and produces at least temporary remissions for these patients. "Previously treated advanced cancer" means widespread metastatic cancer that has already shown resistance against current therapies. Basically, this is end-stage cancer, with next to no options for the patients. If a treatment approach has been found, it will be extended to more patients and improved. Of course, they won't just rest on their laurels. Most advances in cancer treatment (which have together added many years to the lives of cancer patients) are actually much smaller than this: a few weeks added to life expectancy here and a small improvement to the survival rate there. But they steadily add up.
ourmandave 10y ago
Forget flying cars. I'd love to live in a future where we can say, "Remember when cancer was a thing people had to worry about?" And the anti-vaxxers would be stupidly blessed to not know what it was like.
- kartan 10y ago
  > "Remember when cancer was a thing people had to worry about?" As bacterial resistance to our antibiotics is growing we could get to this point where some one will say "I was really worried that it could have been an infection, but it was just cancer". That will make our movies an literature strange to people from the future as characters react to diagnostics in a completely different way that the one expected.
- apathy 10y ago
  Hey if they have their way, we'll all "continue to study" HPV vaccines so that more girls can die of cervical cancer. Fuck those cynical monsters. I don't wish people ill lightly, but they're taking chances with the lives of their children and of others, and I just can't stand that.
  - Tharkun 10y ago
    They mess up 'herd immunity' and should be locked up in padded rooms. I don't mind if they want to fuck themselves up, but they're jeapordizing the health of everyone they come in contact with.
    - nikolay 10y ago
      I don't think you're correct. If you're vaccinated, you can't get harmed by that pathogen anyway. Only those who choose not to get vaccinated, can get infected, but by refusing to get vaccinated, they should be waiving some rights, or have to pay some deductibles. What I don't get is why unvaccinated children are not allowed in California schools as they supposedly can't harm the vaccinated ones.
      - 10y ago
wbkang 10y ago
Just to clarify, this immunotherapy is legit science has nothing to do with the typical "immune system booster" bullcrap.
refurb 10y ago
To some folks this may not seem like much of a benefit, but these improvements add up over time. I could only find this example, but in the last 40 years, the 5-year survival rate for breast cancer patients has gone from ~75% to 92%. All of that benefit was recognized at once, but rather incremental benefits added up over time. I wish I could have the table I saw for colorectal cancer. Really amazing. We're talking average overall survival going from 6 months to 5 years in the span of a few decades. This isn't the one I was thinking of, but it's a great example.[1] [1]https://www.bowelcanceraustralia.org/images/Bowel_Cancer_Australia_Advocacy_Therapeutic_Progress_660.jpg https://www.bowelcanceraustralia.org/images/Bowel_Cancer_Aus...
- danieltillett 10y ago
  Unfortunately a large percentage of this increase has been from detecting early cancers which push out the time to death by pulling back the time of detection - we are not having an impact on the course of disease that the numbers would suggest. I hate 5 year survival as a metric. We should be targeting 10+ years survival (or death from any other cause) as a metric. Five years is just too short a time to know if you have beaten cancer.
  - sachingulaya 10y ago
    For measuring survival my old lab championed the Kaplan-meier estimator for its ability to censor non-cancer causes of death. The 5yr survival can be heavily skewed if patients are dying from secondary causes such as heart attacks, getting hit by a bus, etc. Oftentimes patients with cancer have other serious comorbidities.
    - danieltillett 10y ago
      Exactly. Most people getting cancer are pretty old. Time to death might make sense in paediatric cancers, but not in 80 year olds.
  - refurb 10y ago
    Unfortunately a large percentage of this increase has been from detecting early cancers Do you have a source for that? I've also seen data for stage IV cancers and they show the same improvement. Those weren't caught early.
randcraw 10y ago
If you have cancer, as I may still do (after prostate surgery), PD-1 and PD-L1 immunotherapy simply is NOT a game changer. On average, you live another 6 months, but only if you pass a screening to get the treatment, which most patients fail. So in practice, even with these drugs, the outcome of getting cancer is significant only in a statistical sense. Hardly a breakthrough. I also happen to work for one of the two pharmas making these drugs, and it PISSES ME OFF no end how much overpromotion this advancement is getting. Fact is, if you have cancer, you're still going to die, at best a year later than if you were on chemo. So the lucky few who pass immuno-screening and then get these drugs will benefit mostly by avoiding chemo, not by living significantly longer, much less getting cured. Added to its modest actual outcome, the COST of this treatment is insane - profiteering of the worst kind. Charging a dying person $80,000 for an extra 3-6 months of life while promoting the drug as a 'breakthrough' is just plain wrong. It's a violation of the Hippocratic oath. And it's caused me to lose the little bit of my remaining faith in the value of working in this industry. 'As good as it gets' is a pitiful rallying cry when battling cancer, IMHO.
- feelix 10y ago
  It seems like the PR engine is on overdrive for this drug. And it looks the BBC are spewing it out without giving it any thought at all. Or perhaps the reported was paid? I'm not saying it has no value, I'm saying that their PR is wildly out of control and it's reflecting on the poor state of journalism more than the efficacy of the drug. Here is a scathing review of it and the PR engine behind it from the NYT just a month ago, ironically: http://www.nytimes.com/2016/08/09/opinion/cancer-drug-ads-vs-cancer-drug-reality.html http://www.nytimes.com/2016/08/09/opinion/cancer-drug-ads-vs... OPDIVO is another name for nivolumab. No one should call a cancer treatment drug a 'game changer' unless it literally cures cancer in something like 90% of cases. Otherwise it's spreading false hope and it is actually immoral - if you consider that nearly everybody has been affected by cancer either directly or indirectly.
  - danieltillett 10y ago
    Actually any drug that cures people with cancer even a small percentage is a game changer. A drug that cured 5% of all cancers would be fantastic given most drugs just delay progression with very bad side effects. Our metrics are really skewed - we reward companies that develop drugs that increase average life expectancy by a few months in a large percentage of the target population and which cure nobody, not those that cure even if it is only a small percentage of the target populations. The really bad thing is we are doing almost nothing to develop treatments that prevent cancer in the first place (well nothing gets to the clinic). The three really big advances in cancer treatment in the last 100 years have been the HPV vaccine, Hep B vaccine / anit-Hep C drugs, and antibiotic treatment of Helicobacter (stomach cancer). All of these are preventive treatments that have “cured" millions of cancers.

137 points by sjcsjc 10y ago

Apparently, these tumors proliferate because they are able to trick killer T cells into not attacking them. The antibody, nivolumab, inhibits this signaling pathway so that the T-cells are capable of attacking the tumor. From: Gettinger SN, Horn L, Gandhi L, et al. Overall Survival and Long-Term Safety of Nivolumab (Anti–Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non–Small-Cell Lung Cancer. Journal of Clinical Oncology. 2015;33(18):2004-2012. doi:10.1200/JCO.2014.58.3708. Programmed death 1 (PD-1) is an immune checkpoint receptor expressed on activated T cells, which normally serves to dampen the immune response to protect against excessive inflammation and the development of autoimmunity. However, in the setting of malignancy, PD-1 signaling, driven primarily by adaptive expression of programmed death ligand 1 (PD-L1) within the tumor, inactivates primed T cells that recognize tumor-specific antigens, allowing tumor growth and metastasis. PD-1 pathway blockade with monoclonal antibodies offers a novel approach to restoring T cell–mediated antitumor immunity, with the potential for application across a broad population of patients with NSCLC. From the article: In a trial of more than 350 patients, published in the New England Journal of Medicine, 36% treated with the immunotherapy drug nivolumab were alive after one year compared with 17% who received chemotherapy. That seems like a small improvement rather than a "game changer."

JoshTko 10y ago
Doubling survival rates while having far less severe side effects along with proven effectiveness on multiple different types of cancer is definitely a major breakthrough. This is also based on human trails and not rats in a lab.
- agumonkey 10y ago
  That sentence is such a pleasure to read.
- danieltillett 10y ago
  I wish most cancers treatments were tested in rats in the lab - most of the time they only get tested in inbred mice which are a terrible model for human cancer.
deleted 10y ago
[deleted]
ekianjo 10y ago
> That seems like a small improvement rather than a "game changer." It shows you are not really aware of the state of Cancer drugs these days. Drugs that can make 20~30% patients live 3 months longer are usually considered pretty good, doubling the percentage of survival in ADVANCED cancer is certainly unheard of.
- OrthoMetaPara 10y ago
  That's a pretty pathetic standard for "good" Chimeric Antigen Receptor therapy seems like more of a "game changer," given that it's a new therapeutic direction. This is just another monoclonal antibody.
  - apathy 10y ago
    Spoken like someone who hasn't been following the Kite trials... Also of note: just like good ol' mAbs, you need a target for CAR-T cells. And BiTEs, and BiKEs, and what have you. Also also of note: the approaches that took pediatric ALL and adult APL (among others) from 5-10% survival to 90-95% survival weren't single pronged. (Good thing, too; I've seen patients who seemed ideal for CAR-T die when their malignancy outran the engineered cells) The majority of progress in real-world outcomes has arisen from combination or sequential therapies, incrementally improved to decrease toxicity and maximize efficacy. Which is to say, incrementally advanced. Last: per the above, you can use the two together. If a tumor is actively suppressing T cells, it isn't going to dissolve from CAR-T cells without a fight. There are additional tactics useful for "priming" the immune system, but in the end I don't see a lot of solid tumors melting away in trials of CAR-T cells (feel free to correct me). Do take a look at the Kite trials and how they're structured. When you have to condition a patient with fludarabine to hit outcomes (at all) that's not a wonder drug. It's another tool in the toolbox. A necessary and useful tool, but a tool, not a magic wand.
    - apathy 10y ago
      Hey, just so I'm not a total hypocrite, it turns out that you can "turn off" PD-1 and PD-L1 response in CAR-T cells (at least in mouse models, https://www.jci.org/articles/view/83092 https://www.jci.org/articles/view/83092 ). In the end I stand by my contention that it's a tool and it needs to be used for the right jobs, but it's a very versatile tool. I work on immunosenescence and immune stimulation (the real thing) in oncology, and I happen to believe that we do many patients a disservice by nuking their immune systems with chemo and then relying on things like TKIs or BiTEs to pick up the mess. But it's also important to keep in mind that Gleevec alone didn't get rid of CML, and the way ALL and APL were managed up to 95% cure rates is by adding a little poison (As2O3, methotrexate, etc.) to the brew (asterisk) to finish things off. It's a delicate balance. I think it always will be. (asterisk: ok more like a metric fuckload of poisons for ALL. But the real trick is "resurrecting" the patient with leukovorin after folate starvation essentially kills them.) http://blogs.sciencemag.org/pipeline/archives/2016/07/08/car-t-deaths-cannot-be-good http://blogs.sciencemag.org/pipeline/archives/2016/07/08/car... Look up the SuperMAB saga for more cautionary tales. Plenty of people have died from chemo and immunosuppression too (nobody benefits from lungs full of aspergillus and a gut full of C. diff). If it were easy, somebody would have figured it out already :-)
nsgi 10y ago
Twice the number surviving one year without the side effects of chemotherapy seems like a pretty big improvement to me, although there are a lot of news articles prematurely hyping "cures for cancer" that will probably never see the light of day.
- charlesism 10y ago
  Well, that's the problem with relative numbers. If my absolute chance of survival increases from 0.1% to 0.2%, I'll take a pass.
  - PakG1 10y ago
    Would you choose nothing? If not nothing, why wouldn't you choose the option with a slightly higher chance of success and fewer side effects?
    - charlesism 10y ago
      It depends on how well studied the treatment is. If it's been on the market for 70 years, I'd take the chance. Otherwise, why risk waking up one morning with a tail, or having my arm fall off ;)
      - rangibaby 10y ago
        Because you are going to die pretty quickly either way if you have terminal cancer. At least if you try a new treatment you could theoretically help other people in the future live for longer, and other people who will get very, very rich. lol
        charlesism 10y ago
        If news like this brings people hope, I suppose I shouldn't complain too loudly.
        10y ago
yaakov34 10y ago
It's a very big improvement, relative to most cancer treatment advances, assuming it holds up and produces at least temporary remissions for these patients. "Previously treated advanced cancer" means widespread metastatic cancer that has already shown resistance against current therapies. Basically, this is end-stage cancer, with next to no options for the patients. If a treatment approach has been found, it will be extended to more patients and improved. Of course, they won't just rest on their laurels. Most advances in cancer treatment (which have together added many years to the lives of cancer patients) are actually much smaller than this: a few weeks added to life expectancy here and a small improvement to the survival rate there. But they steadily add up.

ourmandave 10y ago

Forget flying cars. I'd love to live in a future where we can say, "Remember when cancer was a thing people had to worry about?" And the anti-vaxxers would be stupidly blessed to not know what it was like.

kartan 10y ago
> "Remember when cancer was a thing people had to worry about?" As bacterial resistance to our antibiotics is growing we could get to this point where some one will say "I was really worried that it could have been an infection, but it was just cancer". That will make our movies an literature strange to people from the future as characters react to diagnostics in a completely different way that the one expected.
apathy 10y ago
Hey if they have their way, we'll all "continue to study" HPV vaccines so that more girls can die of cervical cancer. Fuck those cynical monsters. I don't wish people ill lightly, but they're taking chances with the lives of their children and of others, and I just can't stand that.
- Tharkun 10y ago
  They mess up 'herd immunity' and should be locked up in padded rooms. I don't mind if they want to fuck themselves up, but they're jeapordizing the health of everyone they come in contact with.
  - nikolay 10y ago
    I don't think you're correct. If you're vaccinated, you can't get harmed by that pathogen anyway. Only those who choose not to get vaccinated, can get infected, but by refusing to get vaccinated, they should be waiving some rights, or have to pay some deductibles. What I don't get is why unvaccinated children are not allowed in California schools as they supposedly can't harm the vaccinated ones.
    - 10y ago

wbkang 10y ago

Just to clarify, this immunotherapy is legit science has nothing to do with the typical "immune system booster" bullcrap.

refurb 10y ago

To some folks this may not seem like much of a benefit, but these improvements add up over time. I could only find this example, but in the last 40 years, the 5-year survival rate for breast cancer patients has gone from ~75% to 92%. All of that benefit was recognized at once, but rather incremental benefits added up over time. I wish I could have the table I saw for colorectal cancer. Really amazing. We're talking average overall survival going from 6 months to 5 years in the span of a few decades. This isn't the one I was thinking of, but it's a great example.[1] [1]https://www.bowelcanceraustralia.org/images/Bowel_Cancer_Australia_Advocacy_Therapeutic_Progress_660.jpg https://www.bowelcanceraustralia.org/images/Bowel_Cancer_Aus...

danieltillett 10y ago
Unfortunately a large percentage of this increase has been from detecting early cancers which push out the time to death by pulling back the time of detection - we are not having an impact on the course of disease that the numbers would suggest. I hate 5 year survival as a metric. We should be targeting 10+ years survival (or death from any other cause) as a metric. Five years is just too short a time to know if you have beaten cancer.
- sachingulaya 10y ago
  For measuring survival my old lab championed the Kaplan-meier estimator for its ability to censor non-cancer causes of death. The 5yr survival can be heavily skewed if patients are dying from secondary causes such as heart attacks, getting hit by a bus, etc. Oftentimes patients with cancer have other serious comorbidities.
  - danieltillett 10y ago
    Exactly. Most people getting cancer are pretty old. Time to death might make sense in paediatric cancers, but not in 80 year olds.
- refurb 10y ago
  Unfortunately a large percentage of this increase has been from detecting early cancers Do you have a source for that? I've also seen data for stage IV cancers and they show the same improvement. Those weren't caught early.

randcraw 10y ago

If you have cancer, as I may still do (after prostate surgery), PD-1 and PD-L1 immunotherapy simply is NOT a game changer. On average, you live another 6 months, but only if you pass a screening to get the treatment, which most patients fail. So in practice, even with these drugs, the outcome of getting cancer is significant only in a statistical sense. Hardly a breakthrough. I also happen to work for one of the two pharmas making these drugs, and it PISSES ME OFF no end how much overpromotion this advancement is getting. Fact is, if you have cancer, you're still going to die, at best a year later than if you were on chemo. So the lucky few who pass immuno-screening and then get these drugs will benefit mostly by avoiding chemo, not by living significantly longer, much less getting cured. Added to its modest actual outcome, the COST of this treatment is insane - profiteering of the worst kind. Charging a dying person $80,000 for an extra 3-6 months of life while promoting the drug as a 'breakthrough' is just plain wrong. It's a violation of the Hippocratic oath. And it's caused me to lose the little bit of my remaining faith in the value of working in this industry. 'As good as it gets' is a pitiful rallying cry when battling cancer, IMHO.

feelix 10y ago
It seems like the PR engine is on overdrive for this drug. And it looks the BBC are spewing it out without giving it any thought at all. Or perhaps the reported was paid? I'm not saying it has no value, I'm saying that their PR is wildly out of control and it's reflecting on the poor state of journalism more than the efficacy of the drug. Here is a scathing review of it and the PR engine behind it from the NYT just a month ago, ironically: http://www.nytimes.com/2016/08/09/opinion/cancer-drug-ads-vs-cancer-drug-reality.html http://www.nytimes.com/2016/08/09/opinion/cancer-drug-ads-vs... OPDIVO is another name for nivolumab. No one should call a cancer treatment drug a 'game changer' unless it literally cures cancer in something like 90% of cases. Otherwise it's spreading false hope and it is actually immoral - if you consider that nearly everybody has been affected by cancer either directly or indirectly.
- danieltillett 10y ago
  Actually any drug that cures people with cancer even a small percentage is a game changer. A drug that cured 5% of all cancers would be fantastic given most drugs just delay progression with very bad side effects. Our metrics are really skewed - we reward companies that develop drugs that increase average life expectancy by a few months in a large percentage of the target population and which cure nobody, not those that cure even if it is only a small percentage of the target populations. The really bad thing is we are doing almost nothing to develop treatments that prevent cancer in the first place (well nothing gets to the clinic). The three really big advances in cancer treatment in the last 100 years have been the HPV vaccine, Hep B vaccine / anit-Hep C drugs, and antibiotic treatment of Helicobacter (stomach cancer). All of these are preventive treatments that have “cured" millions of cancers.