“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...
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.
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.
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.
>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.
>Over time, the mean overall survival has improved from two months in 1973 to five months in 2015. Regarding long-term survival, a clear rise in 2yS is
noted, increasing from 2.6% in 1973 to 12.9% in 2013 (latest
year of which 2yS data can be calculated; Figure 1 and
Tables 1 and 2), occurring mostly after the mid-1990s. A
more modest increase is seen in the 5yS, from 0.7% in 1973
to 3.2% in 2010.
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.
> 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.
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.
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.
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.
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.
> And eating meat's fine (from a health perspective, if not ethical necessarily). We've been eating it for a couple of millions of years.
The current theory is that we developed sweating and bipedal walking to be endurance hunters, i.e. running after a prey animal until it is too exhausted to run any further. Tool use and development were also driven in part by hunting (spears, atlatl, bow and arrow, skinning knives etc.). Overall humans are omnivores, as evidenced by tooth layout. Some populations still manage to live on primarily meat-based diets (Inuit), albeit with some difficulties.
The main issue is the amount of meat: Hunting was difficult and dangerous, limiting how much meat we got. Being able to eat meat every day for almost every meal is a recent development and is a major difference to prehistorical diets. Plus, factory-farmed meat is significantly different from free-range animals w.r.t fat, hormone and antibiotics content.
I always find it baffling appealing to the fact that "eating meat is lindy" - i.e. something stone age humans and us did for hundreds of thousands of years, hence healthy, at least it won't kill you.
Because it ignores the fact that average life expectancy was significantly less than it is today - why would you want to take stone age humans as health role models? In fact average life expectancy almost doubled globally from high 40s to high 70s only very recently - well after we stopped eating meat all the time.
In 1924 the President of the United States’s son died. A man with access to the best medicine and doctors of the time during an insdustrialized age was not able to save his 16 year old son. He died from a bacterial infection…on his toe…that he got from playing on the White House lawn barefoot. In 1924 they were not able to save him from such a “simple” ailment. We underestimate the advancements in modern medicine and how easy it was to die historically. You could be the fittest, strongest vegetarian in 300BC and bad piece of bread could end you. Correlating meat consumption with life expectancy is just foolish.
I would assume the early diets would be feast and starve. You kill an animal and the entire tribe gets to feast for a few days, then you don't eat a whole lot until you kill another animal. Salt eventually flattened this out by being a preservative.
I'm sure there were gathering of berries and plants to fill in between the feast. I mean they were called hunter / gatherers.
> Plus, factory-farmed meat is significantly different from free-range animals w.r.t fat, hormone and antibiotics content.
A version of that argument applies to most things you would buy at a grocery store, e.g. modern apples are a lot sweeter than what our ancestors would've been accustomed to.
Yes. Curiously, it seems the Mediterranean diet helps you live longer, unless you are poor. The hypothesis is that poor people just eat a shitty version of the Mediterranean diet (think cheap fruit and veg, with less fresh) because they can't afford the decent one and so don't get the benefits. I think many of the studies are but sufficiently fine grained to pick out the nuances.
> eating meat's fine... We've been eating it for a couple of millions of years.
The behaviour of ancient humans doesn't necessarily indicate what will keep us modern humans healthy into old age, though. Do we even know whether they ate meat everyday?
Personally speaking, I will generally put on too much weight if I follow my appetite and don't count calories or follow some kind of plan. That's true even if I eat "real", home-cooked food.
This is true. The early humans likely just ate one meal a day, and were moving a lot. They also ate when they got hungry and not necessarily when it's time for "lunch".
> We've been eating it for a couple of millions of years.
My grandparents were farmers before farming became industrialized. If you look at how much meat they ate, it's very little compared to current generations.
Plus, what the cows and pigs ate in those days was very different than what they feed them today. I know of a farmer that raises a cow for his own consumption, and that one gets different food than all the rest. That should tell you enough already.
So the 'eat mostly plants' is very relevant for todays generation, even more so than before.
I’d roll back a bit on meat. It can be very fatty, particularly red meat. And it does significantly raise risks of various diseases, including cancer. If you’re going to eat it, I’d be very selective about the types and sources you consume.
I'd say this is intentionally missing the point. Where you draw the line between homo sapiens and the previous predecessor is subjective and largely arbitrary. The point is that we and our evolutionary ancestors have been eating most edible things we could get our hands on for as long as we go back.
You're fighting some pretty hard core straw men here. I haven't mentioned cardiovascular disease nor actually anything related to the good or the bad of consuming meat anywhere in my comment. HN is not the right place for flamebait.
> I’d roll back a bit on meat. It can be very fatty, particularly red meat.
Fat is not bad. We decided it was on the flimsiest of evidence and suspect "plausbility" arguments (eating fat makes you fat, obvs) and the subsequent attempts to prove the hypothesis in large scales studies have come up empty-handed.
> And it does significantly raise risks of various diseases, including cancer.
I significantly doubt that, the evidence, such that it is, is only found in highly confounded epidemiology that does not allow you to make that claim.
> If you’re going to eat it, I’d be very selective about the types and sources you consume.
Fair enough.
> Humans didn’t exist millions of years ago…
Google "how long have humans been eating meat". Not saying it's right, but it contradicts your point.
Saturated fat (the most prevalent fat in meat) is causally connected to cardiovascular disease. This is based on a huge amount of evidence and, if you are going to discount it, I suggest you also should discount the whole field of nutrition, because this is the close to a scientific fact as we can get.
For the record, I _do_ think that the whole field of nutrition should be discounted.
In the popular imagination we to tend blame journalism for the "one minute x causes cancer, the next minute x cures cancer" style flip-flopping, and I don't doubt some blame is due. However, the underlying science is hopelessly confounded and generates spurious small effects that are probably artefacts of the data than real effects. If this wasn't the case, how do you explain the constant self-contradiction and almost complete equivocality on every issue on these matters.
What is the causal connection you are talking about? I hope not the saturated fat, clogs the arteries, etc, etc. Everyone believed that 50 years ago, no one will in another 100 years. But persuade me; show me the unequivocal science and I'll change my mind. My understanding is that the efforts to show this effect have not worked.
We have mendelian (genetic) studies that attest the causality of this link, ie. people who are naturally born with low LDL have less CVD. Not sure why you think this is not a compelling narrative.
> And eating meat's fine (from a health perspective, if not ethical necessarily). We've been eating it for a couple of millions of years.
Our mouths are too small for the number of teeth we have. A few million years is a lot of time in evolution, but it's still catching up with the invention of cooking.
> Our mouths are too small for the number of teeth we have.
Is that a general thing?
I was under the impression those of us from the British isles had a problem because of mixed heritage due to repeated invasion: we've managed to inherit a tendency for smaller jaws from southern influences and bigger teeth from north/west Europe.
I read somewhere that modern jaws don't stick out enough because we don't chew enough tough stuff growing up. We were evolved to chew roots a fair bit.
