5 ms·

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

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!

semenko 3y ago
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 https://meetings.asco.org/abstracts-presentations/219805 ] P.S. Hi Chris! (I think I picked up a summer student from you last week!)
- haldujai 3y ago
  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.
earthbee 3y ago
1.4% of all cancers is still a huge number of people helped in absolute numbers given around 40% of people will get cancer.
giantg2 3y ago
"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?
- netrus 3y ago
  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 3y ago
    Yes, and?
- chrisamiller 3y ago
  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!
imiric 3y ago
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 3y ago
  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 3y ago
    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 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-peptide-vaccine https://padiracinnovation.org/News/static/design-your-own-pe...
ramraj07 3y ago
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 3y ago
  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.
- londons_explore 3y ago
  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.
- waboremo 3y ago
  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.
londons_explore 3y ago
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 3y ago
  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 3y ago
    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 3y ago
      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.
      - frankchn 3y ago
        There are reasons why drug approval can be slow and conservative: https://en.wikipedia.org/wiki/Thalidomide_scandal https://en.wikipedia.org/wiki/Thalidomide_scandal
        londons_explore 3y ago
        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.
krona 3y ago
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.
lm28469 3y ago
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

semenko 3y ago

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 https://meetings.asco.org/abstracts-presentations/219805 ] P.S. Hi Chris! (I think I picked up a summer student from you last week!)

haldujai 3y ago
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.

earthbee 3y ago

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

giantg2 3y ago

"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?

netrus 3y ago
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 3y ago
  Yes, and?
chrisamiller 3y ago
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!

imiric 3y ago

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 3y ago
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 3y ago
  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 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-peptide-vaccine https://padiracinnovation.org/News/static/design-your-own-pe...

ramraj07 3y ago

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 3y ago
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.
londons_explore 3y ago
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.
waboremo 3y ago
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.

londons_explore 3y ago

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 3y ago
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 3y ago
  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 3y ago
    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.
    - frankchn 3y ago
      There are reasons why drug approval can be slow and conservative: https://en.wikipedia.org/wiki/Thalidomide_scandal https://en.wikipedia.org/wiki/Thalidomide_scandal
      - londons_explore 3y ago
        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.

krona 3y ago

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.

lm28469 3y ago

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