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It is argued in the article that the survival rate didn't go up, but rather how it was measured: earlier detection means a longer period of survival since detection.

You argue that there was rapid progress in the last decade. The article agues the opposite (over decades even). It does this with citations and meta analysis where they find that much of the 'rapid progress' is not replicable. The article doesn't say that immunotherapy is not meaningful, but it does say it is over sold where there is hardly evidence of their benefit.

You also argue that the cost will come down, however there is no evidence for this. To the contrary even: according to the article it is going up significantly without any indication of improving.

Why do you state that the "bizarre claim" of not having improved treatment is "just wrong" without providing any supporting evidence for this?

All these arguments are just arm chair discussions by people who have literally zero knowledge or involvement in cancer treatments. The overall 5 year survival rate has increased significantly and for some types it has increased multiple-fold thanks to new drugs. And regardless, even in types with lower success rates the side effects are generally way more manageable than traditional chemotherapy.

If we diagnose earlier, it's expected that the 5Y survival rate improves even if the patient dies at the same age as she would have in the counterfactual.

Sure, that can show up in aggregated statistics. But it used to be that there was no treatment for all sorts of metastatic diseases. Now there are. That's not a function of earlier detection. This isn't made up; we have real RCTs demonstrating this stuff....

The people who don't know what they are talking about (or are maliciously feigning ignorance) are those who look at 5 yr survival without considering the effect of increased surveillance/screening. https://en.m.wikipedia.org/wiki/Lead_time_bias

You have to distinguish between screening detected cancer and symptomatic cancer. 5yr srvl rates say little in the former case but they are relevant for the latter. You'd really prefer having skin cancer today than ten years ago.

Your short exchange of arguments is a good example of what goes wrong in the public discussion.

I don't understand what you mean by "detected cancer" and "symptomatic cancer". Eg if a cancer is already detected then by definition it is impossible to screen for it.

(Screening detected) Found during a routine/annual colonoscopy/mammogram/etc...

vs

(Symptomatic detected) Hey, what is this lump here? Why am I so tired? etc...

I see, it should have been written "screening-detected" to be as clear as possible.

Yes, the latter is more likely to be comparable over time but it will still have issues with changes in how likely someone is to report it to their doctor, etc.

Look, just because a bias exists doesn't mean that it explains every single bit of improvement. We have randomized controlled trials showing that these drugs work.

Immunotherapies have a significant increase in survival rates of metastatic cancers i.e. cancers that were for the most part not detected early.

Re: cost - you're conflating two different things. The cost of new drugs at the time of introduction has gone up. The new drugs of 2020 are more expensive than the new drugs of 2000. However, with a few high-profile exceptions, the cost of any individual drug goes down over time once generics are introduced.

The expensive new drugs of today are the affordable generics of tomorrow. Biologics are genuinely expensive to manufacture, so the cost of the current generation of immunotherapies will remain substantial, but it will ultimately drop to a fraction of what it is today.

Re: survival benefits - population level data about overall survival is tricky to get right, and issues like earlier detection leading to longer measured survival without actual benefit are real. And I'm sure that if you tweak the statistics just right, you can argue that all of the advances of the last 50 years have accomplished nothing. But that ignores a hugely important fact: we have randomized controlled trials showing that people who get these drugs live longer than an identical population that doesn't get them. I was going to spend a while finding citations, but let's go with the comment /u/dannykwells just posted:

"This article is absolute 100% bullshit.

-Metastatic melanoma: used to be lethal, now 50% cure rate.[1]

-Non small cell lung cancer: same, now around 25% [2]

-Breast cancer used to have a terrible prognisis, now 75% survive. [3]

-Not to mention the myriad of blood cancers with new, strong, cell therapy treatment options with 40-50% durable cure rate.

I don't know this person, but seriously, whoever he is, fuck you dude. Millions of us work day and night trying to improve care, and 99% of us arent getting rich.

[1] https://www.nejm.org/doi/full/10.1056/NEJMoa1709684

[2] https://www.nejm.org/doi/full/10.1056/NEJMoa1801946

[3] https://www.breastcancer.org/research-news/20100930"

Except for one throwaway sentence about life extension averaged across 72 drugs, the huge point the author is missing is that the mortality rate is not what matters. The drugs aren't curing cancer - they're extending the lives of those with cancer, even though those same people eventually die of cancer. That won't show up in the mortality rates that aren't improving, but it's a very important positive effect of the drugs, particularly if that extended period of life can be at an acceptable quality. The industry actually measures its success by "quality adjusted life years," not by mortality, and I think that's the correct measure.

They say it’s two months on average.

This is one of those cases of huge variation between each case which makes the average useless. Metastatic melanoma can go upwards of 5 years while others might still be futile.

Would you not agree that spending hundreds of thousands for a few additional months of fairly low standard of living (even if higher than before) is wasteful on the larger scale?

That depends. As long as new drugs provide incremental impact, the benefit should be cumulative over time. Maybe not the area of healthcare spend with the highest ROI, but not a waste in isolation

> The drugs aren't curing cancer - they're extending the lives of those with cancer,

They often aren't doing that though, and if they are they're only doing it on average for a couple of weeks and are causing significant side effects. That "on average" means that for some people they're shortening life.

> particularly if that extended period of life can be at an acceptable quality

It usually isn't.

https://www.bmj.com/content/357/bmj.j2097

The author doesn't wave away the benefits. He says they are real but only apply to specific cancers which account for a small fraction of those diagnosed. Are his statistics wrong? It seems you benefited, but this isn't a counterargument.

I'm not sure how that's even relevant since any life saved counts( and this isn't a valid argument against releasing a new drug). Anyway yes, depending on the country of course but e.g. metastatic melanoma which was a death sentence has much better survival rates nowadays. You can also look up the small cell carcinoma 5 year survival rate with nivolumab for example. A similar thing is happening with more specialized drugs applied in specific stages of other cancer types in which case yes, the point that it's a small fraction of cancers holds true, but again, how is that an argument?

This seems, then, like another good example why it doesn't make sense to talk about cancer as a single epidemic, but a set of similar diseases, some of which we've made better progress on than others.

100% agree. In fact, even specific cancers are really a collection of disease. For instance, breast cancer is many different diseases defined by different mutations/receptors and with correspondingly different treatment approaches.

So I'm looking back over what he wrote:

> Immune therapies, which seek to stimulate immune responses to cancer, have generated enormous excitement. Two researchers won the 2018 Nobel Prize for work related to immune therapies, and a new book, The Breakthrough: Immunotherapy and the Race to Cure Cancer, claims that they represent a “revolutionary discovery in our understanding of cancer and how to beat it.”

> According to a 2018 report in Stat News, drugs firms aggressively market immune therapies, and patients are “pushing hard to try them, even when there is little to no evidence the drugs will work for their particular cancer.” A 2017 analysis by oncologists Nathan Gay and Vinay Prasad estimated that fewer than 10 percent of cancer patients can benefit from immune therapies, and that is a “best-case scenario.”

Perhaps he's implicitly acknowledging that there are benefits, but in an article that essentially claims that cancer treatment doesn't accomplish anything, I interpreted it as being dismissive of the benefits. Maybe your reading of it is more reasonable.

The analysis underlying the 10% figure is basically correct. In fact, I think that article [0] is a narrower form of what this article would be if it were better: a harsh acknowledgment that immunotherapy, as the most meaningful breakthrough in the last couple decades, is being overhyped. The benefits are real, but writing books about it with subtitles like "The race to cure cancer" is deeply irresponsible.

Again, though, it's a matter of interpretation. They derived that 10% figure basically by multiplying: ~31% of cancers have approved use for immunotherapy, and it averages a 26% response rate. That 31% is a bunch of solid tumor cancers that didn't really have any particularly effective options beforehand. So for the 1/3 of least tractable cancers (~600k cases per year in the US), we now have something that benefits a quarter of patients. Is that enough? No. But it's still pretty amazing.

[0] https://www.statnews.com/2017/03/08/immunotherapy-cancer-bre...

My understanding is that immunotherapy has been shown to work great for cancers without solid tumors and results have been disappointing with solid tumors. It isn't that it's marching steadily forward and will eventually have been shown successfully everywhere.

I think people running down John Horgan's editorial keep citing successes -- multiple myeloma! cured! -- but aren't addressing his overarching argument, which, as I understand it, is that people are being sold false hope in the majority of cases -- familiar cancers like breast cancer, lung cancer, prostate cancer, colo-rectal cancer -- which has the negative consequences of impoverishing them and increasing their suffering for negligible benefit.

To be clear, I don't have any horse in this race aside from insurance bills.

Most of the indications for immunotherapy are cancers with solid tumors. This source [0] is a bit dated (2017) but it contains a chart showing which cancers had an indication for immunotherapy at the time, and they're almost all solid tumors. The initial approvals for the big immunotherapy drugs were for melanoma and non-small cell lung cancer.

[0] https://www.statnews.com/2017/03/08/immunotherapy-cancer-bre...

2017 is a bit dated?

The first immunotherapy was approved in March 2011. An article from 2017 listing diseases with approved immunotherapies misses fully 1/3 of the years (3 out of 9) in which immunotherapies have been approved.

Makes some sense, but that got me wondering if medical guidelines are going to start getting updates every few weeks like web browsers do.

>The timing is particularly ironic, coming after a decade of particularly rapid progress. The survival advantage conferred by immunotherapy is very meaningful

Can you post some resources that support this with numbers?

>this piece is a remarkable sequence of exaggerations, fallacies, cherry-picked data, and hand-waving.

Could you point me to the fallacies and exaggerations in the article?

There are a lot of statistical fallacies like this:

> The current age-adjusted mortality rate for all cancers in the U.S., 152.4 deaths per 100,000 people, is just under what it was in 1930, according to a recent analysis.

The US is a very different population than it was in 1930 in ways that go beyond age. If you want to make a statement like this to point out that changes to lifestyle (e.g smoking/obesity) can totally offset medical progress, then go ahead and make that argument explicitly. But simply citing the headline mortality number to argue "LITTLE NET PROGRESS AFTER 90 YEARS" is unjustifiable.

Edit: As far as evidence of efficacy, here's a more-or-less random clinical trial showing a meaningful survival benefit for melanoma patients given ipilimumab (the first cancer immuotherapy):

https://clinicaltrials.gov/ct2/show/results/NCT00636168?view...

Note that ipilimumab is no longer the standard of care for melanoma as pembro has even higher efficacy.

There are a lot more trials out there if you're inclined to spend time looking through results.

A lot of times with cancer the best course of action is to do nothing. We try to treat a lot more late stage cancers now that have very low success rates than we used to.

The side effects are easy to dismiss when you survive. When you watch someone go through it and they don’t survive, it’s worse than had you done nothing at all.