Cancer Drug Proves to Be Effective Against Multiple Tumors | Hacker News Reader

Cancer Drug Proves to Be Effective Against Multiple Tumors

nytimes.com

131 pointsseibelj35 comments

I hate these articles. They give people a lot more hope than they probably should.

Keytruda/pembrolizumab is not new. It's the same drug that Jimmy Carter famously took for his melanoma. It and Opdivo/nivolumab are PD-1 inhibitors that are amazing developments in treating late-stage cancer that doesn't respond to chemotherapy.

They're also not the miracle that news articles like to breathlessly push. This one does a decent job of pointing out that this is the first time a drug has been approved to treat cancer based on its genetic profile, rather than the type of cancer. That's an awesome development!

But then you get language like this:

"All carried genetic mutations that disrupted the ability of cells to fix damaged DNA. And all were enrolled in a trial of a drug that helps the immune system attack tumors.

The results, published on Thursday in the journal Science, are so striking that the Food and Drug Administration already has approved the drug, pembrolizumab, brand name Keytruda, for patients whose cancers arise from the same genetic abnormality."

Compared to the abstract:

"Objective radiographic responses were observed in 53% of patients and complete responses were achieved in 21% of patients."

That's around the 30% success rate these drugs usually have. They're great, and they can change your life - if you're one of the lucky ones. If you have a family member that needs this treatment, I hope it works.

But it's a lot of money and a lot of hope for a treatment with some rough side effects that for the average patient will either do nothing or give them a few more months to live.

It's a development, a great one, but the reports really need to rein in their enthusiasm. I'd be curious to see the entire statements the doctors in the article made, because I imagine they were more tempered than the selected quotations imply.

Shame on the author, who really should know better given her background[0]... The bar for science journalism, imho, is dirt-low. As long as it doesn't claim vaccines cause autism or climate change is bunk, it seems to pass as valid.

I feel like when articles like this get written, it's the success of the university's PR team. Frankly, I think this kind of behaviour by universities actually hurt them in the long run.

[0] "Gina Kolata is a reporter at The Times, focusing on science and medicine. Her training is in science: She studied molecular biology on the graduate level at M.I.T. for a year and a half and has a master’s degree in applied mathematics from the University of Maryland.

Her work at The Times has led her to be a Pulitzer finalist twice — for investigative reporting in 2000 and for explanatory journalism in 2010."

(via https://www.nytimes.com/by/gina-kolata)

It's not just the reporter, and I wouldn't want to single her out.

"Important incremental progress in ________" just doesn't get an article in the Times.

Part of the key, in both the trials and I hope in the clinic, is that they can use genetic/antibody screening to determine whether one of these PD-1 inhibitors will help you against a cancer... however, it's complicated both for scientific and ethical reasons, when you're running a trial and treating patients.

See the excellent Drug Discovery blog _In The Pipeline_ by Derek Lowe:

http://blogs.sciencemag.org/pipeline/archives/2016/08/23/not...

http://blogs.sciencemag.org/pipeline/archives/2017/05/25/an-...

That is awesome. I hope that the people who worked on this drug make a lot of money. I would rather people who cure cancer become billionaires than people who write selfie-taking apps.

¿Porqué no los dos?

Because the world really only needs two selfie-taking apps, and that's me pontificating generously.

just looking at the paper: http://science.sciencemag.org/content/early/2017/06/07/scien...

they won't.

they won't see a red cent. the drug companies will, of course.

This is a great move toward biomarker-driven, tumor-site agnostic targeted therapies in oncology. I attended ASCO 2017 last week, where LOXO showcased data from larotrectinib in a variety of adult and pediatric indications with Trk-fusions. The waterfall plot is fairly impressive, and I'd be shocked if this drug was not the next to be approved across cancers based on biomarker status alone. A decent summary about it here: https://endpts.com/loxo-takes-center-stage-at-asco-with-its-... Company presentation here: https://www.loxooncology.com/docs/presentations/Hyman_Larotr...

And together with that, the FDA is adopting to precision medicine, adding new ways of testing drugs:

http://www.xconomy.com/national/2017/05/30/woodcock-new-appr...

Which could open new paths, not only in cancer but other types of diseases.

This is great, but in general when it comes to cancer, we need to focus more on putting in fire extinguishers and sprinkler systems primarily, and then building better fire fighting equipment secondarily.

Much of cancer is caused by smoking. Not only lung cancer but 12 different types have been implicated by smoking, IIRC. In the US warning labels have been on cigarettes for more than 50 years, yet people still start smoking.

In NYC, they implemented WHO's MPOWER program with great success. This includes raising the cost of tobacco through tax, banning smoking in public places, very, very strong anti-smoking ads and more. Yet, the Federal tax on tobacco is only about $1.

Tax something too much and you'll create a grey market. Then we can throw people in jail for selling loose cigarettes or maybe just choke then to death.

And next, we introduce a "big portions" tax on fast food meals and a minimum steps-walked-per-day quota for every US American?

Imho smoking, just like drinking or binge eating, are symptoms for far more common problems with wich everybody deals differently, like stress and mental imbalances.

Add to this the fact that some people seem to be genetically more prone to addiction [0] and there is really no easy solution to any of this. In that regard, raising taxes on tobacco feels like a real sucker move because nicotine is considered more addictive than heroin[1].

While it might outprice the addict from his/her drug, it doesn't deal with the actual problem and most likely will result in the addict looking for something else to feed his/her addiction.

[0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2715956/

[1] http://www.nytimes.com/1987/03/29/magazine/nicotine-harder-t...

> "...like stress and mental imbalances."

About half of tobacco consumed in the US is by people who are mentally ill and/or alcohol abusers because they are self-medicating for their illness. They are very heavy smokers. 90% of people with schizophrenia, 60% of those with severe depression.

That said, we should be helping these people with other treatments instead of smoking.

Also, there are other ways of dealing with stress (such as exercising) that using cigarettes. I live in NYC which can be very stressful, but only about 14% of adults and 7% of teens smoke.

>That said, we should be helping these people with other treatments instead of smoking.

Indeed, but that would require a far more holistic approach than just dealing with the issue of smoking, it would require us to admit that stress and mental illness are becoming increasing factors in our modern urban lives but not everybody is equally equipped to deal with that, sadly it feels like we are a long way off from that point.

There has been some progress on stopping smoking.

https://www.cdc.gov/tobacco/data_statistics/tables/trends/ci...

>"Mismatch-repair deficiency predicts response of solid tumors to PD-1 blockade"

I looked in the paper [1] and didn't see any plot of "mismatch-repair deficiency" vs "response of solid tumors". Neither did I see any plot like "model predicted response" vs "actual response". I'm not really motivated to look into it any further, but be careful with this one.

[1] http://science.sciencemag.org/content/early/2017/06/07/scien...

I'm between two sides on this. Access to new life saving medications is fantastic and therefore should be celebrated. On the other hand, cost of the drug makes it inaccessible to a wide range of people.

Maybe someone more knowledgeable than me can explain: do we as a society aim to improve public health on the cheap, or go headfirst into personalized medicine, knowing that we will be spending way more?

I'm pretty sure people dying of cancer suddenly stop caring about philosophical questions about resource allocation. This is an unequivocally good thing - like that other expensive miracle drug, Harvoni.

To save the time of others looking this up:

> Harvoni is used to treat hepatitis C genotypes 1, 4, 5, or 6. This medicine is for use in adults and children who are at least 12 years old or who weigh at least 77 pounds (35 kilograms).

source: https://www.drugs.com/harvoni.html

It cures Hep C, works faster and better than the current, horrible treatment, and because of that, costs $100,000 for a course of treatment.

It's a fucking miracle.

Current US cash price is $33,000.

(https://www.goodrx.com/harvonihttps://www.goodrx.com/harvoni )

There is also increasingly coverage from Medicaid programs.

Not when your surviving family will be paying the bills for decades.

I think there's false premise here that cancer has a single magic cure and we just need to focus on researching that instead of this expensive "personalized medicine."

Cancer is a complex beast, and what we term cancer is really a whole class of diseases with a plethora of underlying causes, some of which we have a basic understanding, and others which we are only starting to understand. Saying we are treating "cancer" as a whole makes as much sense as saying we're treating "fever" or "pain." So what's billed as personalized medicine in cancer at least is really an entirely correct attempt to dig a layer deeper to understand the actual genetic variations that lead the cells to overmultiply, then attempt to address those root causes, numerous as they may be.

We're currently still in the early stages of immunooncology, and the instruments are still blunt, but already more precise and informed than the chemo/radiation world.

As for the cost side, breakthrough R&D like this is not cheap (hundreds of millions to billions), and manufacturing of humanized antibodies (the drug itself) ain't cheap either. We somehow need mechanisms in place so biotech research continues to take these big risks. It is however a completely valid question to ask how we can better derisk this kind of research to the right degree so that certain gaps in the market (e.g. diseases with no cure) can be researched and filled. Big pharma fills that derisking role for the vast majority of smaller biotechs and research labs, often buying up IP and running the hyper-expensive Phase 3's with a 90% chance of failure. The FDA/EMA have the most power in derisking for big pharma, with their very difficult job of balancing the derisking and encouraging research vs safety.

Over time I'm sure the cost will decrease for immunooncology as we improve manufacturing and have get more data on their safety and efficacy profiles in the wild.

>"what we term cancer is really a whole class of diseases with a plethora of underlying causes"

No, this is a new "talking point" come up with by cancer researchers due to their slow progress. Cancer research is up there with social psychology in terms of reproducibility problems, why not deal with that before claiming "it's so complex":

http://www.nature.com/nature/journal/v483/n7391/full/483531a...

http://www.nature.com/news/cancer-reproducibility-project-sc...

http://www.sciencemag.org/news/2017/01/rigorous-replication-...

Cancer is one disease, characterized by, amongst other things, aneuploidy: https://www.ncbi.nlm.nih.gov/pubmed/15549096

Detect and target the aneuploidy and you can have a general anti-cancer therapy.

More than likely we do the years if not decade or more of expensive such medicines until the balance on knowledge is sufficient that churning out variations becomes cheap enough its viable for all.

Think of like EVs, (early adopters of any tech for that matter) those with merely acceptable range were expensive for what they delivered but they are gradually becoming more efficient and at better cost levels. They won't be there for years to come but the people who paid this up front and helping those five to ten years down the road.

Wait, does this mean that these cancers were cured? If this drug makes the cancer completely visible to the immune system, wouldn't that mean that every last cancer cell would eventually be destroyed?

"After taking pembrolizumab, 66 patients had their tumors shrink substantially and stabilize, instead of continuing to grow. Among them were 18 patients whose tumors vanished and have not returned."

BUT

"Just 4 percent of cancer patients have the type of genetic aberration susceptible to pembrolizumab. [But that adds up to a lot of patients: as many as 60,000 each year in the United States alone, the study’s investigators estimated.]"

and from the abstract of the paper itself:

"Objective radiographic responses were observed in 53% of patients and complete responses were achieved in 21% of patients."

We don't know that "this drug makes the cancer completely visible to the immune system". It could easily be that, say, 0.1% of the cancer cells don't become visible for some weird reason, or they accidentally develop a protection against the immune response. It would look like complete elimination of the cancer on scans and in blood markers, but could come back in a few years.

Only way to know for sure is to wait.

Ah, that makes sense, thank you.

I asked repeatedly about these mines of treatment for my uncle. No doctor listened. I'm voided now.

You don't talk to random doctor. You talk directly/contact docs running the trails. They will tell you what is possible. If isn't possible in the US for brain-dead/financial/bureaucratic reasons, once you get the details look for reputed cancer centers abroad who are willing to do it. You will be surprised how many docs will respond to you over email.

The doctors in charge of my uncle didn't and that is the largest issue.

Other researchers did, a good percentage did, some didn't but I can't expect 100% time spending for my email so that's ok. I was surprised but you're right they do answer a few times.

Back to the issue: if first medical caretakers don't listen, then your family won't listen, because they trust the hospital religiously, albeit schizophrenically too [1]. Which means someone will die sooner than necessary.

[1] scary disease put everything back to primitive human emotions. My family, and even I, were constantly dancing between "they don't do enough" "thank you so much". My aunt even thought nurses would poison her husband if she rubbed them the wrong way. But in the end, hospital gets the vote, and somehow when death wins.. doesn't matter who was right or not.

My dad was lucky to get a drug for his lungs he has an uncommon deadly disease called IPF (and also COPD). It was a combination of doctor, insurance and drug company but in the end he was approved and was given the drug. People networking is as important in health as IT it's who you know.

I know I was "researching" (Internet, I'm not a doctor) everything you get desperate when you hear your family member only has a few years. You even consider alternative mumbo jumbo think well maybe it may work.

Studies and trials are rare in my small town and region but if you can I'd search, ask, impose, network do whatever it takes have no shame!

You didn't mention if your uncle was still living if so I wish you and your uncle good luck and good health.

Well, I wasn't clear above, but sadly nature reclaimed my uncle, he's now ashes. I thank you very very much for asking and wish you the best of luck. It's a very weird and sensitive subject.

About your comment:

1) indeed networking is massively important. You talk to someone out of the blue, it's hard; you say you've been directed by <acquaintance> and the discussion is now relaxed and open.

2) indeed, you have to forget about shame. Just insist politely. It's hard at first but with time it goes.

3) I feared becoming too emotional and trusting things that would reinforce my belief. So I stuck on the usual venues: pubmed, nih, nci, etc etc. And even then, every topic or paper, I would check citation, publication date, previous or more recent validation/invalidation. Research lacks counter studies and sample so one academic paper is not enough.

After this screening, I then pinged various people about these findings and what they thought about it, to again, not pursue my own dreams. The issue is, 10 doctors ~= 10 point of views.

3) clinical studies were barely starting in my uncle case (one doctor told me about israel), he was against this because he thought he would be a guinea pig suffering for their profit. Which isn't false but we could have delayed death a bit. We all felt it was way too quick.

ps: all of this just gives hint about the complexity of the real world. So many pieces working at the same time, politics, economy, research, companies, doctors, networks .. nothing fits perfectly, and if you have to turns the gears on your own it takes deep faith to never stop. I wish I did more, but since it's the first time, I couldn't know if I was crazy and foolish or if I should harass doctors a bit more. My opinion is now clear: never stop; be sensitive, but never stop. (that's also the quality of a leader.. which is as old as important in human groups)

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