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.
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.
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.
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.
The reason it is a game changer in we are now trying to cure not just increase survival. Once you have a method that can cure people with advanced cancers that all other treatments types fail on you have a game changer.
I'd certainly like to think that's the case, although unfortunately it does not seem to be. If you read the article I posted in my initial comment, for example, it seems like this involves value combined with PR BS.
If you think that's not the case and it truly is a game changer please do share why
The immunological drugs really are game changers. Up until now we have had three basic ways of treating cancer: cut, irradiate or poison. These basically never work on advanced cancers, or cancers that come back after initial treatment.
The immunological drugs turn the immune system against the cancer and this approach can cure cancers that are untreatable using other methods. It is still really early days, but the immunological drugs are able to take patients that are weeks from death, and for which everything else has failed, and cure them.
What we really need to know if why it does not work for everyone, but it provides a crack into which we can hammer a wedge.
Well this drug is curing people with terminal cancers - something we have not ever been able to do before. Game changer does not have to mean we have perfection, just the previous approach is no longer valid and we are tackling the problem in a new way.
In the field, immunological drugs have given investigators hope that we know that cancer is able to be cured and we now just have to figure out the best way to do it - in the past we really didn’t have an approach that had a chance of making cancer a curable disease. Sure there were some approaches that might work on some cancers or some approaches that would hold the cancer at bay for a time, but nothing that gave hope of general cure.
To put it more succinctly, terminal is no longer terminal.
There may, or may not be, quality of life benefits relative to palliative chemotherapy when dealing with late stage aggressive cancers. Though there isn't 'just one' chemotherapy, in general chemotherapy treatments tend to make the patient sick enough that they must be spaced out to allow the patient time to recover from the treatment.
To me, there does not appear to be anything particularly unique to the treatment economics in regard to the US cancer treatment industry. Unfortunately.
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]
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.
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.
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."
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.
> 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.
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.
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.
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 ). 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.)
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 :-)
That is like saying "this is just another GPS guided smart weapon". Just because mAbs aren't new, doesn't mean they don't have enormous therapeutic potential.
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.
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.
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.
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 ;)
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
In order for a medication to even begin human testing, you need to show that you've done a ton of lab work to show that a medication works, and that the side effect profile is probably minimal. So, by the time it's offered to you, the risks of the drug having disarming side effects, or of causing you to join the caudal class, are pretty damn minimal.
Let's revisit which medications have harmful side effects a century from now. It's impractical to run studies with thousands of patients, and we haven't had more than half a century of data on most drugs. Not that there's much interest in replicating studies anyways.
I'm not keen to pop a bunch of pills unless there is significant (absolute, not relative) benefit. Drugs are overprescribed in my part of the world, partly because people assume "cuts risk by 50%" must mean "a lot." It might... it might not.
> "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.
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.
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.
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.
Vaccination is not 100% effective. People for whom vaccines are not effective rely on the majority of others to be vaccinated so they don't come into contact with the pathogen.
In addition to people for whom the vaccine doesn't work, there are certain groups, like those with compromised immune systems, and infants, that rely on herd immunity. There's also the disruption from mass absences if an outbreak does happen. The teacher has to spend time to reteach things because of absences, to the detriment of everyone involved.
I think you're a cynical monster. And, by the way, this is not a binary situation - you either get vaccinated, or you don't.
I'm not per se against vaccines, but I'm against the following I can think of right now:
- To lower insurance costs, we inject infants, and toddlers with many vaccines at a time, often without much space between shots either. My kids are fully vaccinated but on a spaced-out schedule, and our family doctor fully supports this as a smart choice. There are toxins in vaccines and the more you put at once, the greater the toxicity, so, an intelligent person would try to space out, don't you agree?
- Again, to lower costs, all kinds of questionable preservatives were/are used in vaccines - just like with drugs where you have generics and brand ones, I'd rather have choices and pay extra to get a less toxic form if available. Although ethylmercury is pretty much out (mostly thanks to anti-vaxxers), I'm pretty sure there are other better choices at higher costs;
- Hepatitis vaccine given to infants is usually not justified and could be delayed unless justified by a simple blood test;
- Studies just confirmed that tetanus vaccine works twice long as previously thought - why schedules are not immediately adjusted to both cut costs, and reduce risks?
our family doctor fully supports this as a smart choice
I expect he knows less about it than you do. To you, he says this is a smart choice. To the people who just get them all at once, he says that's the smart choice. As a general rule of thumb, doctors don't actually know the current status of vaccination knowledge; especially "family doctors". So long as you're just taking them, he'll tell you whatever you need to hear.
Anyway, lets look at this: "so, an intelligent person would try to space out, don't you agree?"
Let's imagine a situation where there is, in any given week, a 90% chance of catching each of five lethal diseases. There is a vaccine available for each; taking them all at once presents a 1% chance of death. So in this case, spacing out the vaccines is a stupid thing to do. Where this is going is that without more context and information and actually looking at the numbers, the statement "so, an intelligent person would try to space out" is at best meaningless feelgood nonsense and at worst dangerous.
If we gather the actual numbers, we find that the risk from these toxins of which you speak is vanishingly small (considerably less than, for example, driving somewhere) and thus spacing out the vaccines is not something an intelligent person would do. You probably put the child at higher risk of death from the extra trips to the doctor; do you drive there, or cross roads to get there?
Additionally, unspecified "toxins" are not necessarily cumulative. It's quite possible that they have no effect on each other, and no effect on the ability of the host to deal with them. Is that the case here? Do you know? Are you practising evidence-based decision making? This is your child's life, so you owe it to them to do it properly.
> To lower insurance costs, we inject infants, and toddlers with many vaccines at a time, often without much space between shots either.
No, we don't do it to "lower insurance costs". We do it because the things covered by the vaccines are things we want people to be protected against, and if we delay some of them to spread them out (which has no demonstrated benefit, of any kind, to justify it), then necessarily that means delaying some of the vaccines, and delaying the protection that they provide.
> There are toxins in vaccines
Specifics, please. IME, any time someone mentions generic "toxins" without specifics in discussion of supposed health practices, they are shoveling woo.
The only reason you know that Tamiflu is useless is "cynical monsters" like me who bite the hand that feeds them.
As far as spacing doses, just like anything else it's subject to revision.
Nonavalent HPV vaccines produce antibodies against nearly every HPV variant known, reduce the likelihood of HPV integration, and for someone who has verified that at least a quarter of head & neck squamous, almost half of anal, and far better than half of cervical carcinomas show HPV integrations, typically right into the middle of tumor suppressors or onto oncogene promoters, this is a big deal. These cases are preventable. Not preventing them, when it's relatively cheap and available, is (to me) APPALLING.
The antivaxxer pricks are cynical for relying on the rest of us, who are responsible enough to assume a TINY risk to our kids in order to protect them and others, to take the risks so they can enjoy the benefits of herd immunity.
If that isn't the definition of cynical, I don't know what is. It's on a level with the Soviets celebrating the "eradication" of smallpox while internally working to weaponize it.
Provided a child develops appropriate immunity by the time they're regularly interacting with others, I could care less about the spacing. But that's not really what this is about, is it?
If you have kids and you don't get them vaccinated on an appropriate schedule, you are being a cynical prick. If you fight HPV vaccination because it might "make girls promiscuous", you are a cynical prick. You are presuming to judge risks for others, risks which we as a society have determined are unacceptable. And that makes you a cynical prick, if indeed you do it. (Maybe you're playing devils advocate, I don't know. But I really hate this line of reasoning, and on balance, it doesn't hold water.)
Sorry, but Tamiflu is an anti-viral drug, not a vaccine, and it is effective.
Everybody's entitled to their opinion, and instead of low-class name calling, which is what cynical pricks do for a living, use solid arguments, and clever policies. So far, there's being only arrogance from the pro-vaxxer community.
I see. Where's your rebuttal regarding nonavalent Gardasil, the actual topic of conversation here? When you can provide some evidence (any evidence, really) that the immediate risks outweigh the benefits, I'll be impressed.
Meanwhile, enjoying the benefits of herd immunity while other people and their kids take the risks is the definition of cynicism.
The solution is to make the anti-vaxxers liable for any outbreak and make them take out insurance to cover this risk (treat it like a we do car insurance). If the average anti-vaxxer had to fork out $20,000 a year in insurance then we might find herd immunity is quite a lot stronger.
I really ought to clarify this: yes, we absolutely should do follow up studies to make sure HPV vaccines are doing what we think they are (Gardasil for example).
I do not under any circumstances think it's appropriate to delay HPV vaccination incentives to do these studies. If you think about it, the only perfect model organism for humans is humans. As long as it's ethical (IMHO it absolutely is), the right choice is to proceed and monitor; doing both will provide the appropriate data to judge whether we are accomplishing the goal.
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.