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This is a great example of where cancer treatment is headed and why it's so hard - namely that cancer isn't one disease, it's many thousands of diseases.

This is a drug that targets lung cancer (~12% of cancers) and only one type of lung cancer (non-small cell lung cancer, ~80% of cases). It targets a particular mutated gene that occurs in about 30% of that subtype. And then, about 50% of those patients respond.

So do that math, and you end up seeing that treating one of the most common mutations in one of the most common cancers with what is considered very high efficacy still only helps with about 1.4% of all cancers. This is actually an enormous number for this kind of treatment, and there is a long tail of rare cancers that are going to be much harder to find targeted therapies for.

That all said, this currently appears to be an enormous success story, and the kind of treatment options that have been enabled by genomic sequencing of cancers, followed by many years of drug development and clinical trials. It's fantasically exciting to see us continue to chip away at the problem but by bit and grant people longer lives as a result!

Just because this approach works doesn't mean this is the only approach out there. I sincerely believe that this thought has singlehandedly retarded progress towards more generic cancer treatments. Immune checkpoint inhibition is a clear proof that you could make one drug that could attack a wide swathe of cancers. Heck even chemo is proof of that. If this is the research you want to focus on, please go ahead. But don't tell the public the continuous half truth that every cancer is unique with no commonality with any other cancer. They all literally share the same DNA, they can't be that different. Consider the possibility that the entire cancer research community is just too dumb to discover globally effective drugs. Unless you can mathematically prove its impossibility I'll say let's not make that statement.

Signed, a guy who spent most of his PhD studying cancer.

You’re both kinda right, personalized or targeted cancer therapy is definitely an incredibly promising field and the early results in various cancers are promising. Most notably in disseminated disease.

Simultaneously, one of the largest criticisms of osimertinib in resectable NSCLC has been that some oncologists got overexcited about the DFS results and patients have been unfortunately not receiving the traditional standard of care adjuvant therapy (old school platinum based drugs) which have a proven overall survival benefit (until today osimertinib did not, it now possibly does).

Targeted gene-directed therapy is cool but conventional chemotherapy is still really important.

ICIs are magic when they work.

Why shouldn't he tell the public that every cancer is unique? It's technically true, much in the same way it's technically true you studied cancer but have for years been working with entirely unrelated fields to the advancement of cancer research. You're as much of an authoritative figure on this topic as a random person on the street.

Technically true is how most science education got screwed up in every field of science. We went from educators like Carl Sagan and Feynman who would take great pains to make sure they don't just tell technically true statements to most researchers today blatantly saying misleading technically true statements for a living to get grant money. Every second grant and paper nowadays literally starts with a disingenuous generalizing statement about whatever thing they're studying (xx gene has implications for cancer or whatever). No one says anything because it's technically true but everyone knows it's practically bs. After doing this for decades they start believing their own koolaid.

And thanks for trying to question my expertise. Please look up the no true Scotsman fallacy and see if that may apply here.

> They all literally share the same DNA, they can't be that different.

They share the same DNA in the sense that every cell in that body does. But the different types of cancers have different mutations per cell type and the increasingly precise identification of those is the basis of the recent new treatment options. Histological classifications become less and less relevant, instead mutations and subtypes of mutations give directions for treatment paths. So I think that statement is a bit confusing.

There are also cancers where the root cause is not a cell suddenly stopped functioning properly out of nowhere but instead the rootcause is a virus/chemical (that may or may not still be present in the body/cells).

> Histological classifications become less and less relevant

What do you mean by "histological classification" because every interpretation I can think of is very incorrect.

I meant that every cancer diagnosis is done by a pathologist who describes the looks of the cell/tissue and is trained to assign a cancer classification to it. This is currently changing to genetic testing where the underlying mutation (that is causing the tissue changes) is identified. AFAIK the tissue classification is still the gold standard for most cancer types, but I am positive that this will be completely replaced by the new methods. Medicine will not put the cells under a microscope anymore but into a DNA analyzer instead.

That's incorrect.

If you mean diagnosing the type of cancer (e.g. clear cell renal cell carcinoma) we've already been using molecular markers for over a decade now.

Since you mention "describing the look": mitotic rate and local staging (depth of invasion, lymphovascular invasion, perineurial invasion) matter far more than any DNA/type of cancer and this isn't changing at all nor will it ever change.

> They all literally share the same DNA, [...]

Do you mean this literally or figuratively? Isn't one of the serious problems with tumors that the mutation rate inside them goes through the roof? (And then they eventually figure out how to be metastatic?)

Yeah, that guy is wrong. Cancers have many different mutations.

Even a highly mutated cancer will have Less differences than you have from your neighbor so..

Isn't there a high chance that research aimed at one type of cancer will end up transferrable to other types? Either the actual treatment/drug, or at least the methods and approaches to designing the treatment.

Agreed! This specifically is for adjuvant osimertinib for EGFR+ Stage IB–IIIA completely resected NSCLC.

The headline here is really strong -- and the actual abstract is much more sober: "5-year OS rate was 88% with osimertinib vs 78% with placebo" [Full abstract is here: https://meetings.asco.org/abstracts-presentations/219805 ]

P.S. Hi Chris! (I think I picked up a summer student from you last week!)

Very sober given the costs and %age of patients who didn’t receive adjuvant chemo in the initial trial.

Interested to see their detailed results but I’m mildly suspicious this will be AstraZeneca PR buffing underwhelming results.

Thats still 1366 people every day worldwide.

Think about that... If the committee whose job is approving this medicine get results in on Friday, but don't sit down to approve it till the following Monday, then 4098 people die unnecessarily.

It always surprises me how little effort we put into getting things from the lab to the people quicker.

As soon as we have compelling data some discovery (medical or otherwise) might help lots of people, it should be almost a manhattan project type effort to get it into the hands of everyone worldwide asap.

They do fast track drugs if studies show overwhelming success, and it is no longer ethical to keep it from the control group.

Other areas of medecine do do things in a rush - like an ambulance breaking the speed limit to maybe save one guy. Yet we wouldn't allow breaking the speed limit when delivering a new treatment to save thousands of lives.

What's really inefficient is that every trial needs to spend (hundreds of) millions on writing up the whole thing, IRBs and FDA (and additional authorities) paperwork, recruiting, data analysis, etc. while these could all be standardized. (There are companies that do this, but they are just expensive middlemen. There was a great substack (?) post detailing a lot of these, but now I can't find it.)

There are reasons why drug approval can be slow and conservative: https://en.wikipedia.org/wiki/Thalidomide_scandal

Yet the harm from that (10,000) was in many ways tiny compared to the harm from not deploying treatments that turn out to be good.

For example 780,000 people died of polio between 1988 and today. Yet for all that time there has been a cheap, low risk, well tested, near 100% effective vaccine (many in fact). And polio is probably one of the better cases because governments and charities have been pushing it pretty hard.

The polio vaccine has been approved by the FDA during all of that time. Therefore, I don't understand how the deaths during that time provide evidence that the FDA should approve drugs faster.

Edit: Also, polio eradication efforts where a Manhattan project style heroic effort.

It's hard to "dn no harm" when you yeet drugs at people based on maybe being useful.

That's not how capitalism works though

Not sure if you're specifically referring to the drug in this article but osimertinib has been FDA approved for ~8 years and has been part of routine clinical practice for quite a while now.

The system is actually really fast at getting promising cancer therapies into the hands of patients, especially when there aren't good alternatives.

Even if something isn't yet approved and the patient is ineligible for a clinical trial, an intervention can be offered to patients under compassionate grounds/special access.

the FDA face an unenviable challenge: how to promote healthcare innovation without endangering patients?

regulations that are too loose may cause suffering and death while regulations that are too strict will delay or block prevent helpful treatments.

regulating healthcare is extremely difficult and largely a thankless job.

one solution is to approach national healthcare like national security and let people volunteer for treatments like volunteering for the army.

in short, overstate risks but let patients decide.

adopt cigarette-simple consent forms that state in bold words that an experimental treatment is likely to cause death or crippling side-effects like paralysis, blindness, stroke, Alzheimer's, or worse.

perhaps require multiple signatories from family members to guard against irrational behavior.

this protects the FDA while minimizing barriers to innovative therapies and treatments.

> in short, overstate risks but let patients decide.

Then you have to battle the people selling highly marked up snake oil as an 'experimental' treatment - when every expert could tell you this treatment is already well known to be ineffective.

> Then you have to battle the people selling highly marked up snake oil as an 'experimental' treatment - when every expert could tell you this treatment is already well known to be ineffective.

Isn't that easily solved by requiring all experimental drugs and procedures to be provided free of charge with the cost footed solely by the provider?

indeed. this is a thorny problem with no perfect solution.

on the one hand, you may throttle promising treatments and on the other hand, you may increase useless treatments.

publishing results is one way to mitigate snake oil, though this obviously doesn't eliminate the problem.

the general framework is to maximize transparency and freedom.

letting people volunteer for national healthcare like they can for the national army increases freedom, but we must also increase transparency to combat snake oil.

Anyone should be allowed to take any medicine that they desire. The FDA can still approve treatments, the problem with the FDA is that forbid patients from access to treatment they desire.

"1.4% of all cancers"

This actually seems large to me.

Although that is suspiciously large. Looking at the numbers I think it should be much lower. A 51% reduction doesn't mean it helps 51% if the people. In this case it looks like about 10% of the people are effected given the 88% vs 78% survival rates, right? Maybe something like .28% of all cancer?

These are ballpark numbers to be sure, and yeah, my off the cuff comment didn't get that exactly right. I also simplified things quite a bit to try to get the broader point across - Thanks for following up!

I mean, the people who die of cancer are the problem. If 88% survive instead of 78%, 55% of those who would have died survived (taking these numbers just from your comment).

Yes, and?

1.4% of all cancers is still a huge number of people helped in absolute numbers given around 40% of people will get cancer.

In the UK, 21% of all cancer deaths are from lung cancer. Surely this is the more appropriate way to assess efficacy in the context of all cancers.

The way forward then seems to be personalized therapy for each case. There have been some limited trials with CRISPR that look promising, but mainstream adoption is still likely years away.

Personalized therapy might possibly not work for a really long time. Consider each drug to be a code change at heart of the most critical code running the code of your body. Clinical trials are the integration testing and ab testing equivalent of making sure this change doesn't have side effects. Personalized therapy means you have no way of testing in a comparable system. Unless you're gonna clone babies of yourself give them the same cancer and see if it treats them and doesn't kill them (and then pull a Prestige)

I am not a scientist, but there are technologies like taking a specific mRNA or protein and making the immune system primed against it for a specific HLA. This makes it possible peptide and mRNA vaccines personalized for a person (you can choose a protein/mRNA specific to the cancer this person has and for her HLA type.

This looks as enough close to personalized therapy for me. There are prediction tools available online.

https://nextgen-tools.iedb.org

I even coded my own peptide prediction tool a few years ago:

https://padiracinnovation.org/News/static/design-your-own-pe...

With 70 to 90% of cancer being caused by environmental factors I think we have a lot of areas of improvement before reaching for cures

My mother in law has stage 4 lung cancer. Tagrisso is extending her life. The cancer has been shrinking since going on it with few side effects.

Unfortunately stage 4 cannot be cured, and at some point tagrisso stops working. My understanding is the cancer mutates and eventually develops resistance. Then she will go on chemo and her quality of life will go down.

I am thankful for modern medicine that we get some extra time with her.

My father is in this situation with prostate cancer. First line therapies have stopped working and now its on to chemo. I am hoping chemo won't damage him too much.

There are also radioligand therapies like lutetium 177 but they haven't been sequenced on chemo naive patients yet. So soc is chemo first.

I wasn’t involved in this study but the cancer center I just left was one of the sites for the upfront Lu177 vs chemotherapy trial. Speaking casually with the physician involved recently he said the results weren’t promising thus far.

I don’t think this is published yet and I’m not familiar with prostate ca treatment literature so take this with a grain of salt.

my father is in india where they've been giving lu177 ( and others) before chemo for quite a while ( other countries being germany and australia ) . Forums are awash with 'success stories' . There are many clinical trials currently in US and canada. Some have published results showing 'non inferiority' in small sample sizes but most are in progress

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8627907/

https://clinicaltrials.gov/ct2/show/NCT04647526 this one was supposed to publish some preliminary results in q1 2023 but i don't see any updates :/

> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8627907/

Non-inferiority studies aren't sufficiently powered to answer the question but up-front Docetaxel is pretty old-school. My urology days are long behind me now but even in my residency abiraterone/enzalutamide had taken over as in:

> https://clinicaltrials.gov/ct2/show/NCT04647526 this one was supposed to publish some preliminary results in q1 2023 but i don't see any updates :/

This is the trial I was referring to, I don't think they're done with the analysis/writing yet.

I have no numbers or data hence my casualness but our nucs physician was really excited 5 years ago and lukewarm when I recently asked him if they were finally taking over mCRPC care over a beer.

Again grain of salt, but my impression from that convo was it's going to end up another line of therapy (mCRPC treatment is a game of kicking the can down the road as long as possible).

This gets me curious, if we would be sure cancer become resistant at some point.

Why would we give higher dose of the cure at start ? Wouldn’t the body handle it ?

advice on how to catch earlier?

The really crappy part of lung cancer is that it's very uncommon to detect it because there aren't really any symptoms to speak of.

Eventually it will metastasize so some other part of the body and THAT will give symptoms.

When my Mum was diagnosed the Dr. said the bad news is you have cancer in the bones in your neck. The really bad news is that it started in your lungs, and it's way, way to far along to do anything about.

Cancer sucks.

The good thing is in most people (particularly smokers) it is very slow growing.

We also have great non-invasive curative treatment options like stereotactic radiation.

Don’t smokers account for ~99% of cases of small-cell lung cancer, which is by far the worst type to have (very prone to metastasis and grows rapidly)?

Small-cell (SCLC) is definitely very aggressive and more strongly associated with smoking than non-small cell lung cancer (NSCLC), I'm not sure about 99% but that seems too high.

It's fairly rare though, the quoted numbers from SEER are 14% but from a clinical perspective most of us that deal with lung cancer feel that's discordant with our practices and likely an overestimate.

In either case, smoker or non-smoker you're far more likely to develop NSCLC with adenocarcinoma being more common than squamous cell (typically only in smokers for the latter but still less common than adenocarcinoma).

The typical adenocarcinoma most people get has a doubling time of roughly 1-2 years.

> I'm not sure about 99% but that seems too high.

I double checked, only 2.5% of SCLC incidences is from non-smokers.

same here, my mother had cancer in spine when diagnosed, and it came from lung. Already late stage and metastasize. No symptom until it reached the spine and causing occasional pain and lately inability to move her legs.

Died on less than 2 months after that. It sucks.

I'm really sorry to hear that.

My Mum was told that people with her diagnosis survive on average one year. She fought hard through radiation and years of chemo, and made it just less than three years after the diagnosis. Through most of it she was waking me up at 6am to go for a sunrise walk on the beach. I hope I can be that strong one day.

Low dose CT scan for those susceptible.

https://www.cdc.gov/cancer/lung/basic_info/screening.htm

https://www.uspreventiveservicestaskforce.org/uspstf/recomme...

Lifestyle changes for one.

Do you smoke? quit smoking. Do you live in areas with lots of air polution? High levels of radon where you live? Move.

Do you work with a bunch of carcinogenic chemicals? Find something else to do.

You can also get a gene test do see if you're suspectable to certain cancers.

But most importantly: listen to your body. If you feel that something is wrong, take it up with your doctor.

The newest thing is to avoid ground level apartments in a city with traffic if you can.

I’ve been told brake (or tire) dust is the newest suspect for why young never-smokers are developing lung cancer (combined with certain relatively prevalent mutations).

my city apartments are always coated in black dust... several floors up

Any recommendations on a genetic test to check for susceptibility?

weed?

Switch to edibles?

;_;

Not really. Lung cancer is mostly due to smoking or radon. So don’t smoke and get your house tested.

Outside of that, it’s a crap shoot. My mom in law didn’t have either risk factor. PET scans can pick up but each one exposes you to radiation which can also cause cancer. So they generally don’t screen for low risk patients.

My mother is on what sounds like a similar pill (in result, if not mechanism of action) for a different cancer. Had a poor prognosis, genetically tested several times and after a few rounds of conventional chemo the test indicated she could take a daily pill. It’s wonderful, I’m so glad she is alive for her grandchild, for me, and for herself of course. I think she will probably still die “of” her cancer but at this point it has completely stopped the progression of it for several years. The side effects are a bit weird, and a bit bad, but not even THAT bad. Really came out of the blue for us, an unexpected outcome.

I’m writing this live from the ASCO meeting where this was just presented. Osimertinib (TAGRISSO) has truly transformed the way we treat EGFR-mutant NSCLC, having repeatedly redefined standards of care. I don’t have a source handy, but osi used to hold a record in oncology as being the fastest drug to go from IND (trial-enabling) to approval - less than 18 months.

Osimertinib did $5.44B in global sales last year, leading AstraZeneca’s oncology portfolio [0]

[0] https://www.astrazeneca.com/content/dam/az/PDF/2022/fy/Full-...

Can someone explain the numbers to me?

"After five years, 88% of patients who took the daily pill after the removal of their tumour were still alive, compared with 78% of patients treated with a placebo. Overall, there was a 51% lower risk of death for those who received osimertinib compared with those who received placebo."

So 88% instead of 78% without the pill were still alive five years on. I assume that is the maximum range they could test. How was the 51% then calculated?

Edit: thank you all for the explanation. That makes a lot of sense!

If 22% of patients in the placebo group died, and 12% in the test group, then that's a reduction of 1 - (12/22) = 45% in the risk of death over that time interval.

The true value could easily be 51% if the percentages reported in the Guardian were rounded.

You could subtract both percentages by the baseline average risk of death for 5 years at the age group that people are most likely to get this type of cancer.

The article makes the assumption that those that took the placebo represent the typical post removal patient (an assumption).

So, for 100 untreeated patients 22 would die. Now for these 100 placebo patients, if they took the pill, they would die 12 (another assumption that the two populations are the same).

The reduction is (22-12) / 22 = 10/22 is the risk of death if untreated.

The complementary percentage is

12/22 approx 51%.

However this does not come with confidence intervals.

If you think about the numbers as 12% died vs 22% died, then the 51% intuitively makes more sense, although I don’t know if this is the correct explanation. My guess is that 12 and 22 are rounded numbers.

Based on the abstract of the article https://www.nejm.org/doi/full/10.1056/NEJMoa2304594?query=fe...,

I actually think the other explanations are wrong. They are probably reporting the Hazard Ratio, which is more often used as primary outcome for efficacy of drug than 5 year survival. (See for example: https://en.wikipedia.org/wiki/Hazard_ratio)

The hazard ratio, under some assumptions, tries to estimate the relative risk of dying per unit of time. The benefit of this measure is that there is not some artificial cutoff (the difference between a death at 4 years and 364 days and 5 years and 1 day is neglible).

22% of those who took the placebo died versus 12% with the medication. Seems it’d be a 45% improvement with those numbers.

The pricing of drugs is always weird to me. Is there a good book / article / primer on why a drug can cost the price of a good house per person ? Is it just about recouping R&D, does manufacturing requires very rare raw materials, is the bill going up because of regulation, etc... ?

How big a check would a government have to do to just "buy" the rights to a drug ? (Both in the "legal" and in the "an offer the CEO can't refuse" version ?)

All of the above, but my guess would be that the most expensive part is usually running the phase III clinical trial. You have to pay data managers to perform the randomization, train doctors and nurses to administer it, and the hospital for the added time it takes them to run the trial, pay the statisticians that perform the analysis, an agency that helps prepare the application, etcetera. You have to recruit patients, gather informed consent (though that is sometimes done by doctors and nurses). Also, you have to give the drug for free, since insurance companies do not cover experimental drugs. Sometimes patients also receive a fee for participating in the trial. All in all, the median cost of pivotal trials is 50 million dollars. This is the cost after you already did studies to discover the drug, and determine the dosage. Half of these trials fail, and all the previous investments are lost in that case.

[1] https://bmjopen.bmj.com/content/10/6/e038863

the pricing is partially due to a lack of collective negotiation

the government programs carry a lot of weight as a large client but are currently barred from negotiating on prices

part of some US universal healthcare proposals are to just allow existing government programs to negotiate on prices, while simultaneously extending coverage to more people

It costs about $7000 in Europe (the price seems to be similar in different country even though there is no EU wide collective negotiation).

The price in the US seems to be around double in the US. But maybe that just pharma companies do PPP adjusted pricing? e.g. it seems to cost ~1500 in India for instance. Americans are simply much richer and also significantly more on healthcare than people in other countries.

> It costs about $7000 in Europe (the price seems to be similar in different country even though there is no EU wide collective negotiation).

That seems like a monthly price? The treatment regimen in this study is daily for 3 years.

It's hard to find out what drug prices really cost as there are a lot of discounts and negotiations behind the scenes but the best source in this instance would be a cost-effectiveness study which uses local data and happens to be a hot-topic in every national cancer society so is widely available.

EU and US pricing isn't too far off with both being ~130k USD a year give or take.

> it seems to cost ~1500 in India for instance.

There were generics, and there probably still are in parts of the world but they're technically "illegal". AstraZeneca shut down a few and there are pending countersuits against them.

https://www.fiercepharma.com/pharma/astrazeneca-staves-last-...

According to the CDC, 80-90% of lung cancer deaths are linked to cigarette smoking (1). It seems like a simple solution for people to just not smoke...

(1) https://www.cdc.gov/cancer/lung/basic_info/risk_factors.htm#....

'Nicotine releases a chemical called dopamine in the same regions of the brain as other addictive drugs. It causes mood-altering changes that make the person temporarily feel good. Inhaled smoke delivers nicotine to the brain within 20 seconds, which makes it very addictive—comparable to opioids, alcohol and cocaine. This "rush" is a major part of the addictive process.

'When the person stops using tobacco, nicotine levels in the brain drop. This change triggers processes that contribute to the cycle of cravings and urges that maintains addiction. Long-term changes in the brain caused by continued nicotine exposure result in nicotine dependence, and attempts to stop cause withdrawal symptoms that are relieved with renewed tobacco use.'

https://www.camh.ca/en/health-info/mental-illness-and-addict...

There are other ways to consume nicotine which are much less harmful.

Same for lots of dependence causing substances, effects are greatly varied by delivery mechanism. Eg heroin pills used to be quite common over the counter and weren't considered a hard drug.

Vaping should be about as efficient if not more than smoking? Probably not something we should encourage but still way safer than inhaling smoke.

The data isn’t published yet (presumably this was shown during the ASCO conference this weekend) but this is a bit misleading and the results seem underwhelming.

The DFS numbers are not new and known, the reason this is in the news as it’s the first report of OS numbers from the initial ADAURA trial.

I can’t be definitive without seeing the data yet but:

1. Osimertinib is not that new, in the context of curative intent disease (i.e. resectable stage II-IIIA) it is currently (ideally) used post adjuvant chemotherapy (the only treatment to date with an overall survival benefit).

We need clarification on what the placebo arm is and what the subgroup analysis showed. What it should be (and presumably) is an “active surveillance protocol” where patients underwent short course adjuvant platinum based therapy and then followed with imaging. Recurrences are then treated with systemic or locoregional therapy.

As this is an update of the ADAURA trial we know that only 40% of patients received the standard of care platinum adjuvant therapy, this article claims an OS benefit was seen in all groups but we don’t have the numbers for the subset of patients who received appropriate adjuvant treatment.

2. Main criticism of the ADAURA trial thus far has been that the results only report “disease free survival”, while that intuitively makes sense as a metric what we really care about is “overall survival”. There are several reasons but to keep it simple this is now the third generation tyrosine kinase inhibitor, the first 2 also had DFS improvements (albeit not as dramatic) but failed to show OS benefits.

3. Osimertinib is expensive. Following the ADAURA protocol (3 years of adjuvant therapy) would have an incremental cost (ICER) somewhere around ~$3-450,000 per patient. “Willingness to pay” is variable, in most places it’s $50,000/quality adjusted life year. Some in the US are pushing for this to be ~$190,000/QALY (3x GDP).

Based on extrapolated DFS and earlier OS data in the last year it was estimated that the OS would be around 5-6%, based on this threshold a system would need a willingness to pay of ~$320,000/QALY. Conversely, to meet the GDP threshold above OS would need to be ~20%.

In a recent Canadian economic analysis they modelled 6% OS at 10 years and arrived at a ICER of ~$40,000 suggesting this protocol makes economic sense. To my knowledge this is the first report suggesting cost effectiveness and contradicted the Health Canada modelling.

4. Based on this news article, there was an absolute reduction in OS of 10% at 5 years which seems underwhelming given that we know most of the patients did not receive adjuvant platinum based chemotherapy, the OS in the subgroup that received both treatments is what matters here.

From the US analysis, this would still not meet the willingness to pay threshold. The Canadian one would need to be re-run with 5 year numbers to see what the ICER is.

Overall, it’s potentially a very positive result but at face value the OS numbers seem less impressive than anticipated.

If someone has the $ and an EGFR ex19 mutation there is definitely benefit but it remains unclear whether this is cost-effective for a system vs other treatment options we have.

(N.B. These numbers are approximate from my recollection of the literature but I can dig up references if something seems off. For background I’m a radiologist focused on oncologic imaging, this has been a hot topic in rounds/case conferences for a few years now hence my familiarity.)

Can you elaborate a bit on the cost? Why is it expensive? Will it still be expensive after the patents/marketing-exclusivity expires?

I don’t know much about pharmaceutical pricing or drug discovery to offer an informed opinion as to why it’s so expensive ($300/day) or whether that’s justified.

AstraZeneca’s patent expires in 2035 and as a cash cow ($2B in revenue) I would expect they continue to aggressively fight competitors in court.

Imatinib (the 1st gen drug of the same class) went generic a few years ago and is 99% cheaper now.

I assume we’ll see something similar with osimertinib but I can’t comment on whether there’s any secret sauce that makes it different.

Perhaps one of the pharma/biochem HN commenters can offer more insight.

Halfway through the article, they spell out what they mean by "cuts risk of death by half":

> After five years, 88% of patients who took the daily pill after the removal of their tumour were still alive, compared with 78% of patients treated with a placebo.

...which is still remarkable, but doesn't sound quite as good as "cutting by half".

After 5 years, (i) Placebo: 22% mortality, (ii) Daily Pill: 12% mortality.

45% reduction in 5-year mortality. Quite close to “cutting by half”

I just wonder how we've not been able to make a drug to increase lean mass without negative effect on cardiovascular system

https://en.wikipedia.org/wiki/Enobosarm

I’d read some research about this a couple years ago and didn’t remember seeing anything about effects on the cardiovascular system but that does seem like a possibility

Increase your natural T. Doubt you maxed it.

Aspirin, Creatine, l arginine, coq 10, ozempic

L-Argenine is huge for me in competitive cycling. Among many effects, it allows more oxygen to get to my muscles, which can double my range and substantially increase my speed.

Out of all of these, creatine is the closest thing to what OP was describing, but even then it doesn't affect lean mass, it just draws water into muscles and increased endurance.

In lung cancer with a particular mutation.

Still a good news

In other news shares in Marlborough saw hockey stick growth.

These kind of medicines can easily cost 100k euro pp per year.

[flagged]

I thought that death risk was 100 percent, no matter what

99% of all non-smokers die

You need to update those stats

To late for Whalter White, sorry, I mean Heisenberg. :(

> After five years, 88% of patients who took the daily pill after the removal of their tumour were still alive, compared with 78% of patients treated with a placebo.

My chance of living 5 years goes from 78% to 88% by taking an expensive pill everyday with side effects? That's not an amazing thing. If it was 78% to 95% with one or two pills, or a positive healthy lifestyle change, then that's something.

I'm going to push back and say this is garbage. The fact that this is being billed as "thrilling" and "incredibly positive" makes me want to puke. This is par for the course in the cancer industry.

I'm going to call this what it is: an advertisement for two crappy new lines of business. First, we have a new genetic testing business: "Not everyone diagnosed with lung cancer is tested for the EGFR mutation, which needs to change, Herbst said, given the study’s findings." Cha-ching!

Then, we have the actual new business of the pill. What are they going to charge, $50,000 a year?

Imagine if you could choose 2 options:

1. Take a pill everyday. Have side effects. Pay $250,000 2. Don't take a pill. No side effects. Keep the $250,000

If that was the choice I'd bet people in group #2 live longer.

This isn't science or medicine, this is advertising.

Pardon my bluntness, but sometimes anger is necessary to get people to wake up.

> My chance of living 5 years goes from 78% to 88% by taking an expensive pill everyday with side effects?

Reducing the likelihood of death by a half is still something... Of course yeah, the price is pretty insane but besides that it's still a great achievement and a significant step in the right direction.

Pity you have been down voted by people who have not understood one of the common patterns that big pharma utilizes to rake in profits.

Far too cynical. You are incredibly uninformed about the significance of this drug.

I could be wrong. Absolutely. I am always open to more information.

However, I'm usually not wrong about these things. This pattern is so common in big pharma it's an easy bet right now.

Based upon the limited information released I would bet:

1) it has high odds of being very lucrative for a small number of people

2) it will be a net negative for patients^

^ Patients would be better off with more money and using an alternative treatment strategy. This drug is priced at $12,750 per month, according to Wikipedia.

>I could be wrong. Absolutely. I am always open to more information.

You really need not be apologetic, being too 'open' to repeated nonsense from the same entities (big pharma in this case) is not a good thing either.

> I could be wrong. Absolutely. I am always open to more information.

You're still a bit too cynical but there are some nuggets of truth in what you're saying.

With regards to mutation testing: I'm not sure where this Hopkins guy is getting his data from but mutation testing for lung cancer is already standard of care, it's been part of the NCCN guidelines for > 5 years at least.

EGFR is not the only driver mutation and osimertinib is not the only drug that can be used, even for EGFR.

Molecular marker and genetic testing of cancer is unequivocally to the benefit of patients and is not a BigPharma scam, it also has little to do with this specific drug other than that this is one of many gene-directed cancer therapies.

> 2) it will be a net negative for patients^ > ^ Patients would be better off with more money and using an alternative treatment strategy. This drug is priced at $12,750 per month, according to Wikipedia.

Be careful with generalizations like this. This drug is very signficant, you just have to select patients appropriately.

There is no doubt osimertinib works well, if you have unresectable/non-curable lung cancer it can potentially buy the patient an extra couple of years (median ~8 months) over previous generation TKIs and even longer versus conventional chemo. These patients used to just die within a few months 5-10 years ago.

This article, and the trial it talks about, is about adjuvant therapy (i.e. after the surgery) in patients with locally-advanced but curative intent disease that at baseline have pretty good good survival so in this specific use-case your criticism of cost-effectiveness is a reasonable one.

Consider a 45 year old with an EGFR mutation and stage IV lung cancer (unfortunately common these days), an extra 8 months-3 years is immensely significant for them and their families and this is a miracle drug.

On the other side of the spectrum, for a 75 y/o with stage II cancer who underwent curative-intent treatment (i.e. this study population), the argument is much weaker given the costs vs low absolute risk reduction over a long time period. I broke down the financials in another comment.

You're probably right that the numbers won't add up in this trial for this specific patient population, the article + PR releases so far do smell a bit like AstraZeneca buffing somewhat underwhelming results (expectation was that overall survival would look better than 10%) to sell more of an expensive drug, but you're overgeneralizing and it is a very good treatment option in well selected patients. It will also be a great adjuvant treatment option whenever this becomes cheaper like 1st-gen TKIs are now.

Solid response. Thank you for taking the time and providing the additional information.