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!
Signed, a guy who spent most of his PhD studying cancer.
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.
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?)
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!)
Interested to see their detailed results but I’m mildly suspicious this will be AstraZeneca PR buffing underwhelming results.
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.
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.
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.
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.
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?
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.
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 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.
Why would we give higher dose of the cure at start ? Wouldn’t the body handle it ?
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.
https://www.cdc.gov/cancer/lung/basic_info/screening.htm
https://www.uspreventiveservicestaskforce.org/uspstf/recomme...
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.
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.
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-...
"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!
The true value could easily be 51% if the percentages reported in the Guardian were rounded.
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.
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).
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 ?)
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
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.
(1) https://www.cdc.gov/cancer/lung/basic_info/risk_factors.htm#....
'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...
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.)
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.
> 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".
45% reduction in 5-year mortality. Quite close to “cutting by half”
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
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.
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.
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.
