“Statistically significant and highly clinically meaningful” perhaps, but not so much that they can say what that actually means.
My understanding is that of all cancer drugs approved by the FDA between 2000-2016 (around 90 drugs), the median life extension was just over 2 months...
My aunt was diagnosed with stage 4 lung cancer and is only alive because of this drug. It’s a marvel of modern medicine.
My wife was diagnosed in Nov '23. Stage 4. She had a mutation that allowed Tagrisso/osimertinib. There are many mutations, but this one is prevalent in Asian women who have never smoked.
There was a trial published just after her diagnosis that showed progression free survival at 2 years of 57% (chemo+osimertinib) vs 41% (osimertinib).
https://www.nejm.org/doi/full/10.1056/NEJMoa2306434
She's 6 days into the chemo. There are 4 rounds of pemetrexed+carboplatin and then maintenance carboplatin (forever). Every 21 days.
So far, it's been rough, but hopefully her body will adjust and once she's just on carboplatin hopefully her quality of life will be better.
She had few side effects from the osimertinib, but the main one was mouth sores. They're gone now, thankfully.
Another thing people need to know about this: this diagnosis often comes with regular thoracentesis (removal of fluid from the chest). In this case, it's in the lining of her lung, not lung itself.
Advice to anyone in this situation: make all future appointments for thoracentesis, because you don't want to go into the ER/ED to get it done. And, we've stopped allowing residents to practice on her (once it was quite painful).
EDIT:
Forgot to add: carboplatin crosses the blood-brain barrier, as do the cancer cells. The end state for this cancer, even with the above treatments, is usually tumors in the brain.
this one is prevalent in Asian women who have never smoked.
Does that mean the rate is lower for Asian women who do smoke?
My understanding, though not by any means an expert, is that lung cancer that non smokers tend to get is different to that which smokers tend to get.
This is my understanding.
I think they just mean that the incidence is much higher in that group than would otherwise be expected.
Not all lung cancers are related to smoking, but I'm not aware of any where smoking decreases incidence or is protective.
Can you refuse allowing residents to practice on you or your loved ones for better quality of care?
Sure, you can generally refuse any medical care in the US. With respect to residents, It can be as simple as asking and picking the right doctor for your procedure. Their credentials are generally public.
Yes, you can, and the doctors we talked to said it would not negatively impact them.
Hey, best of luck to you both. I've been there with close family members and cancer. It's no fun at all. Easily the hardest thing I've ever had to do in my life was just to care and watch.
Make sure to grab family and friends to help out. The want to help out, most of the time, at least. I know it's hard to ask, but make sure to do it anyways.
And yeah, standard generic advice to take care of yourself too. I hated that advice, as there just was never any time to do so. One thing that helped was to schedule that 'me' time in and make others aware of it. If you put it on the schedule, you'll have a better chance of taking it.
Two tips with MDs:
1) Carry and use a notebook in all MD interactions. Just a simple journal is all. Time, medications given, dosages, MD administering, etc. It's a good back up to have, sure, but you'll likely never use it. The real power is when MDs see you writing things down. They take you more seriously and they take themselves more seriously. I think they think that you'll sue now and have some proof. But who knows.
2) If you're in for a long term treatment (1+ nights) put a big bowl of candy outside the door. Nurses etc. will stop by more often to check up on things and generally seem to like you more. Consider putting cigarettes in there too, depending on if your nurses smoke. Then they will really like you and go above and beyond.
Again, best of luck to you both.
FUCK cancer.
Thanks. Appreciate the tips.
I wish her and you all the strength in the world.
Would you be willing to share a few more details for me to understand? It would help me talk more concretely with my colleagues.
So she had stage 4 lung cancer.
"Is alive only because of this drug":
- Was her life expectancy obviously prolonged? If so, by how much has she exceeded it so far?
- Has the cancer progressed more slowly, halted, or regressed?
Thanks.
I’m not completely read in to all the details but she told me prior to this drug her diagnoses was a “death sentence.” The lung cancer had metastasized throughout her bones. The indication was sudden lower body paralysis caused by a spinal tumor. She had spinal fusion surgery as well. I understand because it’s stage 4 she will never be in “remission” but it has regressed significantly.
Thanks for sharing. At such an advanced stage and aggressive metastasis, for it to have regressed at all... wow. She must have been in so much pain.
My dad was in a similar situation ~10 years ago. Stage 4 lung cancer, although a different underlying mutation (ALK). Prognosis was less than a year. But he got on some new-at-the-time inhibitor drugs (Crizotinib iirc) which eliminated ("no evidence") the cancer. What is left does slowly mutates around the drugs, and he goes in for regular monitoring and has had some radiation therapy to knock down specific growth spots, but he's still here with us.
I can't speak to the one in the article, but the drugs he's on aren't chemo, but they interrupt one of the pathways the cancer is using to infinitely grow. They have side effects, but not bad ones comparatively.
Amazing. Thanks for sharing. Oncology is such a complex field. I imagine discoveries in this field will only advance exponentially due to increasing investments and AI tech.
My wife had stage 4 melanoma. Prior to the newish immunotherapies about 5 years ago, it was a death sentence — 6-9 months life expectancy from diagnosis. Now, it’s 60-70% 5 year survival rate. Unfortunately my wife wasn’t one of them.
In general, these types of cancers spew mets and spread quickly. Many are resistant to chemo, go to the brain (chemo cannot help there) and only respond to high focused radiation like SRS or proton beam.
Immunotherapies essentially suppress checkpoints that cancer cells use to avoid immune response and/or cause your body to target specific checkpoints. I can’t read FT.com, but I believe it’s talking about a targeted therapy that allows your body to control the cancer.
There’s alot of research happening around things like immunotherapy combined with custom versions of Moderna and other vaccines that will significantly improve treatment and save people going through what my wife went through. It’s a good time.
Sorry to hear about your wife. Yes, once those melanomas go deep enough in the skin, they spread everywhere like a plague.
I know there's even researchers creating AI-assisted treatment regimes that match specific mutations, other aspects of people's DNA, and all the immunotherapy drugs, in order to mix and match the best possible solution. Ongoing research and not yet widely available.
I look forward to learning more about the newer developments.
Wow, that's incredible. So wholesome reading a comment like this on HN, makes me more hopeful of the future. Thanks for sharing
That is indeed remarkable. Stage 4 lung cancer usually makes you seek out hospice care.
It feels so good to read a comment like this. Thank you for sharing and I’m really happy for you and your family (and modern medicine that makes it all possible).
It's a great sight to see people outliving research protocols.
Best wishes.
My mom died from lung cancer. It was going to happen, life long smoker.
Dying from LC is a terrible way to go. Your lungs fill with fluid and you slowly drown in your own fluid. The pain meds make you hallucinate terrible thoughts. I wouldn't wish it on anyone.
For the benefit of humanity, I hope this treatment works.
Same with my dad in the 80s. His descent was horrible to witness, in my case at the age of 21. I’ll never know the truth, but I think his doctor took pity on him, dad died very shortly after a push of morphine.
I'll never understand how in this day and age we still allow people to die suffering this way.
How come we are ok with euthanasia for pets but not people?
It doesn't need to be legal to do it. People commit suicide all the time. The government doesn't need to be involved in each and every section of our lives, from cradle to grave.
Those attempts sometimes fail, and then people might be in an even worse condition than they were before. Maybe quadriplegic and/or in a psych ward.
The government is involved in every section of our lives. Births are registered, deaths are tracked, and mysterious deaths are investigated. But in this case, the government is asked to exactly not be involved; just giving licensed professionals* the permission to perform euthanasia under certain conditions.
*: not necessarily doctors if they want to stick to a strict interpretation of the Hippocratic oath
It is allowed in some places. The problem is it's a terrible slippery slope which has been used to get rid of people whose lives were considered to not be worth living.
How come we are ok with euthanasia for pets but not people?
I think because:
- It mostly wasn't an issue we had to deal with until recently because we didn't have the medical techniques to preserve people's lives so long anyway.
- There are some concerns around people being forced into it that require any laws enabling it to be carefully designed.
- Religion providing it's usual function of inertia around societal customs slowing the change.
Pretty much everyone I know under the age of 60 (and many older) support euthanasia for people who have dementia or some other unpleasant condition that affects their quality of life (self-determined, not forced on people), so I'm quietly confident that it will be happen soon.
I'll be pretty mad if it's not available for me if/when I get to the point that I want it!
Because pets are property. There is no concept of consent. Human consent to die vs. pathological suicidal ideation is a very tricky thing.
"We" don't. Here in NL euthanasia is freely available if needed.
Thanks for sharing and sorry to hear that.
My mom was only 56 (2004) and I got a call from the hospice very early in the morning.
At her request, I had tried to take care of her myself for the couple weeks after her diagnosis, but once the hallucinations started, due to her increasing the pain meds, she started screaming one night and the neighbors called the police thinking I was abusing her.
Thankfully, they called a case worker and I was able to get her into hospice pretty shortly after that and then it was just a couple days more at that point.
It was pretty traumatic. One of those life events you never forget. RIP mom.
My family tried home care in the terminal stage, but it was too much for my mom and sister. My mom also had some serious mental illnesses, compounding the difficulty we had as a family. The trauma was so great I did not really hit a normal state of emotional and mental stability until I was about 30.
I was the only one there as he took his last breath, and it still brings tears when I think about it.
Have you gotten therapy for that trauma?
I have. One thing one of the therapists told me was that it is ok to be angry at her for the abuse I took from her growing up, due to her mental illnesses. That worked wonders. Once you get past anger, it is pretty much all downhill from there.
Watching my grandfather die with emphysema at age 12 was the only anti-smoking message I ever needed
Weirdly, my father who has smoked (and drank) daily his entire life (now 78), is still alive and kicking. Camel unfiltered and a lot of vodka.
I never smoked and I was never a big drinker. But, I stopped drinking entirely a couple years ago cause it was just too painful to look at him with his current health issues, and think to myself that I'm going to end up like he is. No thanks, I don't need that poison.
About 20% of smokers escape that way. Enough for everyone to know one, but the odds are still not in your favor.
A friend died of lung cancer. Went from mild cough to funeral in about 5 weeks. 40 yo. 2 pre-teen kids.
Started to look after my own health a bit more.
This is a very welcome development.
PSA: If you have dependents, or think you might, get some life insurance in place now while you're relatively young. I've had too many friends/colleagues pass away unexpectedly without any (or not remotely enough) life insurance, leaving a spouse and young children behind, inevitably turning to gofundme and similar just to get by.
I actually tried that but the ones I've found had explicit clauses against cancer and other diseases in fine print. Apparently they only help if you get hit by a car and alike.
Probably need to make another pass. (I'm in Europe)
Yeah, the comment may have been more US-oriented (where I'm living). I do know a couple colleagues who can't get any term life insurance because of some pre-existing medical conditions. That's not good for them, obviously, but for most others, it makes sense to get something early. Years ago, at 35, I got an $800k 20 year term for about $55/month. Close to 20 years later, we have more savings/wealth, so my family would not be in hardship or having to go begging if I died tomorrow. A 15 year $500k policy now costs me $80/month. I recently got that, but may let it lapse in a few years if we don't need that any more.
FWIW, my policies don't have any specific denials for certain causes of death (particular disease, etc) but I did have to provide medical records (and I'm not in perfect health).
One way around this is group health insurance through employers. Often they allow you to take the policy with you when you leave the employer.
The underwriting is done with a group, so the standards are lower and less intrusive.
Interesting. The few times I've seen that, it's typically something like $20k-$50k, which seems more intended to get you through a few months, catch up on bills, etc, but not "family is financially secure for years". Perhaps you can get more via employer-sponsored plans, it just never was presented to me in the few corporate jobs I've had over the years (but boy oh boy did they try to sell cancer insurance!)
s/health/life/
Also to hijack this thread: if you or a loved one is/was a long-term smoker, take yourself/pressure them to have routine cancer testing. Right now, while our liquid biopsy has limited availability, for most people that means getting CT scans. Lung cancer is very fast moving and survivability is directly related to how early it is detected. The overwhelming majority of people who are eligible for routine CT scans for lung cancer don't ever get them!
The overwhelming majority of people who are eligible for routine CT scans for lung cancer don't ever get them!
Surely there are tradeoffs here, because CT scans use ionizing radiation.
Have CT scans gotten much more efficient (regarding radiation dose) in recent years?
A person with 20 years of smoking history that waits for symptoms before getting tested might as well sign their own death certificate. CT scans aren't something that a person with a low risk profile would have routinely for a wide variety of reasons, which is why bringing an affordable liquid biopsy to market is so important. A lot of work has been done to make CT scans theoretically valuable to a wider audience, but that is not going to translate to widespread early cancer detection in-practice as evidenced by the >90% of eligible patients that never get tested.
Yes. The one specifically designed for lung cancer screening is a 'low-dose' CT scan, that is usually around 1/5th of a standard CT scan. This is similar to the low-dose CT scan used for identifying heart disease, a coronary calcium scan. In fact, there some research showing that a single scan can do both at the same time (https://www.nature.com/articles/s41467-021-23235-4), quite well, especially coupled with ML analysis of the scans.
For both of these diseases, it seems like the small amount of radiation (2-3x normal yearly background) is well worth the radiation risk done twice a decade for low risk (>40 y/o) and perhaps up to yearly for high-risk former/current heavy smokers (>50 y/o), which is the current recommendation. Even out-of-pocket, these scans tend to be very inexpensive (for medical diagnostic tests), at around $150-200.
get some life insurance
Be super careful though, as many insurance companies (not only life insurance) just seem like scams. With you only that finding at the worse possible time, after the event.
The alternative being "try to plan for not having to rely on them", which itself may also not be possible.
Any more details? No history?
Smoker, was always coughing a bit. His grandfather also died of lung cancer, but he didn’t make the connection until it was too late.
Damn it man, here I am reading this at 41 with a mild cough. Thanks for that!
I'm really sorry to hear that - cancer is terrible.
Didn’t Cuba have a vaccine for lung cancer? I seem to recall seeing one in a documentary (maybe a Michael Moore film?)
My father died of lung cancer. I also ran a failed medical tourism company which sent people to get this treatment in Cuba. More modern versions of the Cuban treatment are now few approved in the USA as immunotherapy. Didn’t save my dad
Sorry about your Dad but did it help other people? How many did you send and how many had positive outcomes in terms of prolonged life above the expected outcome?
You might be interested in the Phase IV trials in Cuba, which were published here : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346887/
There was also a published study by Roswell Park, on a few hundred patients many of which flew out to Cuba to take it, but it's only Phase 1, so no efficacy, only safety and antibody titers : https://www.roswellpark.org/newsroom/201903-safety-analysis-...
Since I settled with the trump white house I keep my mouth shut on outcomes. I am Happy I did it
So sorry to hear about your dad!
I also ran a failed medical tourism company which sent people to get this treatment in Cuba
Why did the company fail? How effective was the treatment?
Trump banned it
For those curious, https://en.wikipedia.org/wiki/CimaVax-EGF
Yes, for non-small cell lung carcinomas. Its not a panacea, but seems to be effective.
After observational studies of patients who flew to Cuba to take it confirmed efficacy, phase 2 clinical trials are underway in the US : NCT02955290
It's unfortunate it took this long. If it wasn't for the sanctions, it would certainly already have either finished (or failed, though unlikely) trials.
Still in trials in the US/EU, but it's not useful for anyone over 60 because the immune system is too weak.
Tagrisso earned $5.8bn in sales in 2023 — 13 per cent of AstraZeneca’s total oncology sales — making it the company’s highest earner.
The drug seems to have been approved in 2015-16. If that's the case, why is this announcement of efficacy happening now? A long-term outcome after a short-term tentative approval?
US approval follows the path of one treatment for one ailment.
so if something was useful for 100 ailments, it needs 100 different approvals, and a company willing to attempt doing that
what more likely happens is one treatment is denied for the one ailment the company thought they were tackling, and that one treatment is never pursued again
so there's a lot of waste in this particular approach to protecting the public. I'm not familiar with other approaches.
Why doesn't the company pursue it for other purposes? Sounds extremely narrow, as per the comment above. There may be related stuff where it works as a treatment depending on the endpoint?
because there is always lower hanging fruit at that point.
Even if this was the most altruistic, non-profit funded goal to solve an obscure ailment, once that inevitably fails - and statistically it is inevitably - all capital has been expended, your team's reputation has been spent. You go to something that has more consensus instead of your alchemy concoction nobody's ever head of and wasn't good for the one thing you made it for.
Because it is extremely expensive and complex to pursue each each use. At some point of diminishing returns, it makes sense to let the medical community lead the process of finding and testing uses.
Seems like there's a lot of opportunity with those unused treatments, if you can get the right arrangement of capital. If the company gives up on pursuit, perhaps the'd sell it for less than the R&D cost. Someone could go scoop up 'losers' and find a better way to match them to ailments.
This happens. Drug companies sell off IP and technology quite often.
The bottle neck is you need someone with a better use hypothesis, and a billion dollars to test that. Drug Trials and development are obscenely expensive.
One other facet to consider is that it is already legal to for doctors to the medicine for any of those 100 approvals. those trials serve three purposes, 1) to generate high quality data to support doctor choice, 2) provide defense for medical malpractice suits against doctors, and 3) support insurance reimbursement.
Doctors already have discretion to prescribe Tagrisso for the common flu. However, a doctor that does so will struggle to get insurance to cover it, and will have a harder defense if the patient sues.
It was approved for certain types of cancers and has slowly been approved for more and more types of cancer, basically.
Dec 21, 2020 Approval Tagrisso Approved in the US for the Adjuvant Treatment of Patients with Early-Stage EGFR-Mutated Non-Small Cell Lung Cancer
Apr 18, 2018 Approval FDA Approves Tagrisso (osimertinib) as First-Line Treatment for EGFR-Mutated Non-Small Cell Lung Cancer
Jun 6, 2017 AstraZeneca Presents Tagrisso (osimertinib) Data in Patients with EGFR T790M-Mutation Positive Lung Cancer and Central Nervous System Metastases
Mar 31, 2017 Approval Tagrisso (osimertinib) Receives FDA Full Approval
Nov 13, 2015 Approval FDA Approves Tagrisso (osimertinib) for EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer
It is about Osimertinib, sold under the brand name Tagrisso.
It works (in “statistically significant and highly clinically meaningful” manner) against certain types of lung cancer when administered on early stage.
It was provisionally approved after success in phase 1 trial by FDA in 2015 and by EMA in 2016.
Side effects:
Very common (greater than 10% of clinical trial subjects) adverse effects include diarrhea, stomatitis, rashes, dry or itchy skin, infections where finger or toenails abut skin, low platelet counts, low leukocyte counts, and low neutrophil counts.
Common (between 1% and 10% of clinical trial subjects) adverse effects include interstitial lung disease.
The side effect you didn't mention: mouth sores. It's the only one that my wife had (in the first month). So far, no other problems, though the chemo started last week (see my comment about it, if curious).
That would probably be from the chemo your wife is on rather than the osimertinib. Chemo tends to cause mouth ulcers along with hair loss etc.
No, the chemo started a month after the osimertinib and the sores appeared in that first month. The oncologist confirmed it was a side effect of it.
It works (in “statistically significant and highly clinically meaningful” manner) against certain types of lung cancer when administered on early stage.
What is considered early stage? Pre symptoms?
And what type of success rate are we talking here?
Cancer staging is complex, as one would expect for a wide-ranging category of diseases that follow different courses and cause harm different ways. Stage depends on tumor size, distance of spread, what organs it spread to (lymph nodes are especially worrisome), and how much the tumor cells differ from normal tissue. There is a large manual used by oncologists to record this information, and another large manual for cancer registrars to summarize it.
https://www.cancer.org/cancer/diagnosis-staging/staging.html
There are simplified categories of early/late stages, usually used in public health statistics. "Early stage" here is in situ (hasn't broken out of the tissue where it first appeared) or localized (hasn't left the primary site/organ). "Late stage" is regional (metastasized to adjacent organs) or distant (metastasized to non-adjacent organs, usually through the bloodstream or lymphatic system).
What is considered early stage? Pre symptoms?
Not necessarily. This is generally true for things like kidney cancer, which is really deadly. People don't usually get checked until they have symptoms, which is usually after it's metastasized. But benign tumors can cause symptoms by physically pressing on organs. Benign brain tumors, which can kill, are an extreme example of this.
Side effects do not realy sound bad so, as someone who went through a light, comparatively, chemo I saw a lot worse with other patients. Plus, the alternative is lung cancer in late stages. And you sure as hell don't want that!
It is really good to see progress in cancer treatment so!
That doesn't sound too bad if it can cause lung cancer to regress.
My father has been taking Tagrisso since he was diagnosed with Stage IV lung cancer in January 2022. It’s been able to give him a relatively normal quality of life I don’t think my family would’ve seen otherwise if he’d gone through chemo and radiation.
Just chiming in that I’m super thankful to that these newer treatments are so effective.
That said it’s not cheap and he still has to work to keep his insurance… otherwise it’d be ~10k/mo.
I'm glad that Tagrisso has helped your father.
Do we know how much public funding for Tagrisso that AstraZeneca mugged from the respective citizens of the countries where they operate and how much they're going to sell it back to us for?
If you're honestly interested in the history of Osimertinib (Tagrisso) then this article has a good overview. It specifies the studies involved so that you can dig into funding sources. Generally for drug development, public funding only covers basic science and maybe early-stage trials. The majority of the expense is in phase 3 clinical trials which pharmaceutical companies pay for.
he still has to work to keep his insurance… otherwise it’d be ~10k/mo.
I mean, it'd be covered under the ACA or presumably medicare as well?
So glad to hear your father has made it 2 years. I have hopes for my wife (see my recent comment).
Why are the top comments in this thread all personal anecdotes? Is this reddit now?
Since when is it wrong for people who have personal experience with a topic to share personal anecdotes? And what does Reddit have to do with it?
I was under the impression that hacker news was not a place for sharing personal anecdotes, but rather a place for factual debate.
https://news.ycombinator.com/newsguidelines.html
Please don't post comments saying that HN is turning into Reddit. It's a semi-noob illusion, as old as the hills.
Hey onco-nosology nerds: Is there a cell-typed unambiguous classification system, research, and clinical treatment protocol nexus attempting to capture and disseminate information on all cancer types in a more precise and organized effort?
NCI has the current treatment guidelines for each cancer and is updated when new treatment options become available: https://www.nccn.org/guidelines/category_1
Unfortunately, these are very clinician-focused and are very hard to understand without a medical background. They also don't usually cover experimental treatments that are still in trials, but in some cases can be extremely helpful. I work on an app at Outcomes4Me (https://outcomes4me.com/) that is trying to convert the NCI guidelines into an algorithm so that we can tell patients in simpler terms what their treatment options are based on their specific diagnosis. We also try to find clinical trials recruiting for their specific diagnosis. We've done this for breast and lung cancer so far.
I don't know if this is what you mean, but Foundation Medicine has a biobank of genomic data (HIPAA) with cancer patients' genomic profiles.[1] It's pan-tumor and pan-cancer.
EDIT: if you're looking for more of a "what is the current best known treatment plan for xyz" then this might not be what you're looking for. The standard of care is very much changing very often, I don't know if anyone has a solution for disseminating that. foundation medicine also has a patient-focused side where you can get your own test and get pointed to the treatment for your cancer genomic profile [2]. The societies are probably trying the most to get all of that data available/up-to-date (for example: the American Cancer Society)
[1] https://www.foundationmedicine.com/service/genomic-data-solu...
[2] https://www.foundationmedicine.com/patient/start-with-step-o...
More precise and organised than what?
According to Wikipedia, it depends on a specific cancer cell mutation, T790M, which could also be a forced mutation from using other EGFR tyrosine kinase inhibitors. This alludes how tricky, and how fast, cancer cells mutate and adapt.
> In people treated with osimertinib, resistance usually develops within approximately 10 months.
In my MIL's case it was L858R. T790M also present, effectiveness of drug dramatically increased with presence of both. Osimertinib shrunk the tumor from baseball to golfball, and then her left most lung lobe was surgically removed. She was stage 2 at intake and without metastastis. The drug was not approved for that case in 2021 and she was admitted to an ongoing case study for it.
My sister had the ALK variant of non-small cell lung cancer. The special treatment she got worked until it didn’t, about 16 months. One oncologist said the cancer had likely mutated and the ALK specific therapy was no long effective.
Is there actually some kind of list which shows in a table what kind of cancers are currently treatable by which experimental medicine?
By definition no one knows for certain which types of cancer are treatable by experimental drugs. That's why they're still experimental and not yet approved. But this site has a good list of resources for finding clinical trials that might help.
https://www.cancer.net/research-and-advocacy/clinical-trials...
I predict that ~30 years from now, someone will take all these drugs that have shown some success in treating some cancer, mix them all together at a low dose, and find the combination works better than any of the components.
This is already done. There are many labs currently looking for "synergistic" combinations of treatments.
I -think- this is the study referenced https://ascopubs.org/doi/full/10.1200/JCO.22.02186
I wish there had been something for IPF which is progressive scarring of lung tissue. My Dad died of it after a long battle. The doctor even said it's worse than lung cancer at least for that there are treatments.
The distribution skews right on these things. Median probably is not the right way to think about it
Maybe I've misunderstood, but for the average person that's even worse news, right?
Two months was from clinical trials where there's no doubt that the "thumb is on the scale" in a host of ways, creating an exaggerated estimate of efficacy that would be realised in the real world.
The reality is closer to no life extension, with the remaining lifespan is spent sicker than you'd have been without the drugs.
I dont think that is true at all. The data is pretty clear that lifespan is significantly increasing.
I'm sorry, but two months to five months after 50 years and hundreds of billions of dollars. That was hardly the promise of the "war on cancer"!
To be fair, there are other cancers that are essentially cured. Lung cancer is a particularly nasty one for a number of reasons. It's hard to fight with the laws of physics or biology, so I'm curious who promised you something else.
In general though, I tend to agree that in the US we spend far too much on what essentially boils down to performative end of Life Care. If you ask someone if they would rather spend $200k for 2 months or leave it to their family, I think most people would pick the second option. When someone else is paying, they choose the first option.
"This year marks the 50th anniversary of the “War on Cancer” declared by Richard Nixon, a former President of the United States of America. By signing into law the National Cancer Act on December 23, 1971, Nixon hoped this action to be the landmark legislation taken by his administration. Nixon apparently had confidence that cancer would be conquered in 5 years."
You're right, there are a small handful of unusual cancers that we have cures for, and that's great. And some small progress has been made overall. But a lot of money has been spent, and it has been half a century or more, and we don't have much to show for our efforts.
Nixon hyped up some legislation 53 years ago, few believed the hype, and the hype was clear to the rest very shortly thereafter.
You are right that progress is slow and expensive in a lot of areas.
It seems you are frustrated or angry about it. What do you want people to do? Are we not spending enough on research? Are we spending too much?
Yes, it would be better if we had more complete treatments but it’s far from nothing. I have a friend who was given 6 months to live a couple decades ago, right before a treatment for his not especially rare cancer was approved. He didn’t expect to see his daughter leave elementary school but is still around for her post college career – and as a scientist himself is keenly aware of how much hard work made that possible. We can simultaneously acknowledge that progress has been made but cancer is one of the hardest problems humanity has tackled.
This is mind-bogglingly wrong for most cancers. Several death sentences have been turned into treatable diseases.
You are, again, failing to note that it’s a right skewed distribution. The mean is not what you care about.
In fairness, I was responding to the first sentence in the quote from the article.
It seems relevant, as a patient to ask, on average, how much longer will I live if I take this drug?
To which, an average is a pretty poor way to convey non-normal data.
If you run a year long trial where you flip a coin and immediately kill or save people based on the results, your average survival will be 6 months
To be fair, the Improvement for the tail is pretty Grim too. We have 'only' seen 5 year survival improve from 0.7% in 1973 to 3.2% in 2010.
I think the skewed distribution is less relevant than the sample group. There are limits to what we can expect from medicine. We don't have improved survival after decapitation, but that doesn't mean surgery has been at a standstill.
It would be interesting to look up survival rates for earlier stages. I expect the difference would be more substantial.
Imagine a toy scenario where a cancer will kill 80% of people with it at exactly 3 years, and all 20% remaining will uh live full lives (so say another 20 years).
If you created a drug that shifted the ratio to 60/40, and measured right at the 5 year mark. In a population of 100 untreated people, you'd get like 4080 total months lived (80x36 + 20x60). In a population of 100 treated people, you'd get like 4560 months lived (60x36+40x60).
That's only generating an extra 4.8 months of life per person treated. However, you've doubled the number of people alive at the end of trial.
Now obviously this is a toy example that's probably a bit exaggerated, but this type of behavior is exactly why median/average life extension is an inadequate measure alone.
Yes, but this isnt as negative as it sounds.
That 2 months average is often driven by more people alive at the end of a 2 year trial.
Also, 16 years of 2 month extensions ends up being quite meaningful.
To be clear, those aren't 16 years of accumulating improvements. The median life extension - across all 90-odd drugs - was two months.
I understand that specifically is for stage 4 non small cell lung cancer, but I don't think it's appropriate to cherry pick a single example. There are other cancers and stages we're much more progress has been made.
Sad stats truth: statistical significance does not say much about effect size, and it's misinterpreted by ~half articles.
See https://www.nature.com/articles/d41586-019-00857-9 for more
That's why the "highly clinically meaningful" part of the quote is there.
My understanding is that of all cancer drugs approved by the FDA between 2000-2016 (around 90 drugs), the median life extension was just over 2 months...
An exciting, underrated possibility: therapies in conjunction with each other, even if the therapies are initially studied in isolation. Single-agent chemo doesn't work for many cancer types, but multi-agent chemo often does. The same may be true of the small molecules, antibody drug conjugates (ADCs), and monoclonal or bispecific antibodies being tested now. I have squamous cell carcinoma initially of the tongue, and now of the head, neck, and lungs (https://jakeseliger.com/2023/07/22/i-am-dying-of-squamous-ce...), and I'm on a clinical trial monotherapy at UCSD called MCLA-158 / petosemtamab. But, if I live long enough, which isn't super likely but isn't impossible, there's a decent shot that the FDA will finally approve Moderna's mRNA-4157 personalized vaccine for melanoma—hopefully in 2025. If I can get mRNA-4157 off label and combine it with pembrolizumab (Keytruda) and petosemtamab (assuming the latter is approved, too), that combo may be much more potent than any of the three in isolation, and I've already failed pembro as a monotherapy and pembro + carboplatin + paclitaxel.
And if that combo doesn't work, or has some unexpected negative effect (including death), well, I'm going to die anyway, and the risk seems worthwhile.
As another commenter observed, the median can be skewed by the number of people who don't respond; among those who respond to a given drug, some don't respond, but some live surprisingly long.
In this case, the extension is often far longer. See comment by @kkio. Our oncologist has people that have been on it for years, as well.
Anecdotal, but Keytruda was approved in 2019 when my dad was diagnosed. He got 4 extra years (3.8 of which were pretty high quality) that I can assure you he would not have gotten without it. The progress on lung cancers specifically has advanced quite a bit in the last 10 years.
I think that is a perverse incentive of Medicare so it gets covered in treatment.
The may work better, but the drugs only run the studies to that threshold.
My mom died of lung cancer like 10 years ago and the immunotherapy drugs like keytuda all has those disclaimers.
Her pd1 wasn't a good fit, but some like Jimmy Carter responded really well