[chrisamiller]

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!

[ramraj07]

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.

[haldujai]

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.

[waboremo]

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.

[ramraj07]

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.

[miramba]

> 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.

[bboygravity]

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).

[haldujai]

> Histological classifications become less and less relevant

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

[miramba]

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.

[pas]

> 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?)

[Metacelsus]

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

[ramraj07]

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

[londons_explore]

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.

[semenko]

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!)

[haldujai]

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.

[londons_explore]

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.

[londons_explore]

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.

[seanmcdirmid]

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

[londons_explore]

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.

[pas]

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.)

[frankchn]

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

[londons_explore]

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.

[peteradio]

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

[lm28469]

That's not how capitalism works though

[haldujai]

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.

[panabee]

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.

[londons_explore]

> 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.

[lelanthran]

> 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?

[panabee]

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.

[dantheman]

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.

[giantg2]

"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?

[chrisamiller]

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!

[netrus]

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).

[giantg2]

Yes, and?

[earthbee]

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

[krona]

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.

[imiric]

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.

[ramraj07]

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)

[JPLeRouzic]

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...

[lm28469]

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