Hacker News Board Hacker News, browsed like a classic message board
Live data from Hacker News

Daily pill can double survival time for deadliest cancer, trial shows

theguardian.com

Post reply on HN
Print view View original

41–50 of 62 posts

Re: Daily pill can double survival time for deadliest cancer, trial shows

#41

Post by mft_ »

mrandish wrote: post #9

Totally naive question: is this a situation where stacking the drug with chemo might be even better?

Yes, with nuances.

The recently-read-out trial is in the 'second line' - meaning patients will have received one 'line' of treatment before this - typically chemotherapy +/- surgery. The chemotherapy regimes used for pancreatic cancer can be pretty brutal, and patients can usually tolerate one, max two lines overall. As such, this trial administering only daraxonrasib monotherapy made sense.

The first line trial of daraxonrasib is already underway, and includes both darax monotherapy and darax + chemo arms. (They are combining with a slightly less brutal chemotherapy called GnP, with an eye to the overall side effect burden considering the non-trial side effects that darax also brings.)

It'll be very interesting to see the outcome of this trial; there are some examples elsewhere in oncology where a treatment is recommended by guidelines without chemotherapy over a combination with chemotherapy, as the small survival benefit the addition of chemotherapy brings is seen as outweighed by the additional toxicity.

Re: Daily pill can double survival time for deadliest cancer, trial shows

#42

Post by mft_ »

adrian_b wrote: post #27
infamia wrote: post #18

Earlier quoted context omitted.

> "survival" is the wrong word; its terminal. No one actually knows that one way or the other since some patients were still taking it after the study ended according to the article.

According to the abstract of the article, there were 2 groups of patients. One group had median values of 8.5 months for progression-free survival and 13.1 months for overall survival. The other group had median values of 8.1 months for progression-free survival and 15.6 months for overall survival. Overall Survival (OS) measures the time until death from any cause. Progression-Free Survival (PFS) evaluates how long…

Your numbers are a little off. The NEJM article was published a few hours ago: https://www.nejm.org/doi/full/10.1056/NEJMoa2605555

RAS G12 population mOS: daraxonrasib 13.2 months / chemotherapy 6.6 months Overall population mOS: daraxonrasib 13.2 months / chemotherapy 6.7 months

RAS G12 population mPFS: daraxonrasib 7.3 months / chemotherapy 3.5 months Overall population PFS: daraxonrasib 7.2 months / chemotherapy 3.6 months

> Thus the treatment had provided them a median life extension of about 3/4 years. The lucky ones probably have got more than an extra year.

The 'median' patient in this trial lived ~6.6m longer if they received daraxonrasib. It's worth noting that the performance of the chemotherapy arms was stronger in this trial than previous trials of second-line chemotherapy; whether this reflects better care or a prognostically-superior trial population remains to be seen.

Re: Daily pill can double survival time for deadliest cancer, trial shows

#43

Post by Spooky23 »

stouset wrote: post #17
matheist wrote: post #13

Earlier quoted context omitted.

> The company says that the drug was generally well tolerated, but that’s on the oncology scale. > ... > He’s been on daraxonrasib since early this year, and describes it this way: “. . .it’s a nasty drug. It causes crazy stuff like my body can’t grow skin and so I bleed all out of a whole bunch of parts of me that shouldn’t be bleeding” If you go to that link above, be prepared, because he also looks like he’s had a…

I am in the enviable position to not be actively dying from an untreatable disease, so obviously haven’t seen things from the other side of this sort of situation. But to me, that doesn’t sound like a life worth living. Obviously different people will have different thresholds for when to throw in the towel, and I’m glad that we are finding medicines to allow people to make the choices that align with their own drive…

I’m sorry to hear what you are facing and send any good vibes I can. I lost my wife to a particularly nasty metastatic cancer (melanoma). There were a few complications that delayed her immunotherapy, which ultimately led to her death.

There is a targeted therapy that applies to many melanomas, but hers did not have the mutation that made it an option. Perhaps this treatment will be tweaked and developed to be less awful and offer that gift of time that my wife didn’t have.

Cancer and other diseases are insidious. While she didn’t make it, she had hope. And the reality is her hope was built on the shoulders of countless others who faced certain death and whose experiences led us to the 60/40 odds that melanoma patients have today.

Re: Daily pill can double survival time for deadliest cancer, trial shows

#44

Post by xboxnolifes »

stouset wrote: post #17
matheist wrote: post #13

Earlier quoted context omitted.

> The company says that the drug was generally well tolerated, but that’s on the oncology scale. > ... > He’s been on daraxonrasib since early this year, and describes it this way: “. . .it’s a nasty drug. It causes crazy stuff like my body can’t grow skin and so I bleed all out of a whole bunch of parts of me that shouldn’t be bleeding” If you go to that link above, be prepared, because he also looks like he’s had a…

I am in the enviable position to not be actively dying from an untreatable disease, so obviously haven’t seen things from the other side of this sort of situation. But to me, that doesn’t sound like a life worth living. Obviously different people will have different thresholds for when to throw in the towel, and I’m glad that we are finding medicines to allow people to make the choices that align with their own drive…

I think the two key things to consider is that: (1) humans are quite good at getting accustomed to their current situation, and (2) these degraded living situations generally happen gradually. There's no hard cutoff where one might suddenly think "welp, I've passed my threshold of wanting to live just now". Boiling the frog, if you will.

There are so many different situations I could not imagine happily living in even when I try to, but then I try to think about how I would feel if I was born into the situation from day one. I wouldn't really know any other life, and so it would just be my life. With that in mind, the most troubling thing mostly seems to be what I have perceived to have lost, rather than what I currently have. That helps me understand how you can keep on living. Even when you lose something, you still have what you still have.

Re: Daily pill can double survival time for deadliest cancer, trial shows

#45

Post by YeGoblynQueenne »

s1artibartfast wrote: post #23
stouset wrote: post #17

Earlier quoted context omitted.

I am in the enviable position to not be actively dying from an untreatable disease, so obviously haven’t seen things from the other side of this sort of situation. But to me, that doesn’t sound like a life worth living. Obviously different people will have different thresholds for when to throw in the towel, and I’m glad that we are finding medicines to allow people to make the choices that align with their own drive…

> Still, I can’t help but think that this is the sort of life virtually none of us would choose to inflict on our pets, even if cost was no option. We give them a far more graceful exit from this world than we give ourselves, and I think that’s worth considering. I often think about this, wondering how many of those animals would have chosen death if given the choice, and how often it is simply a way to spare the own…

Always. Everything that pet owners do to their pets is driven by the owner's human feelings and not the pet's animal needs. Obviously, because we can't communicate with the pets and they can't tell us what we want. And we have total control over their lives so we do what we want.

I'm personally particularly upset by the easy conviction with which most people neuter their pets. I can rant for hours on the ethics of that, or the complete lack thereof, in my opinion. I'm shocked there is so little debate on that, even by philosophers and particularly of animal rights activists who really, really should know better than support such a cruel, egregious and obvious violation of an animal's individual existence.

At least in some countries neutering an animal for anything but medical reasons is illegal. Maybe I should move to Norway.

Bonus: great Black Metal scene.

Re: Daily pill can double survival time for deadliest cancer, trial shows

#47

Post by stouset »

YeGoblynQueenne wrote: post #45
s1artibartfast wrote: post #23

Earlier quoted context omitted.

> Still, I can’t help but think that this is the sort of life virtually none of us would choose to inflict on our pets, even if cost was no option. We give them a far more graceful exit from this world than we give ourselves, and I think that’s worth considering. I often think about this, wondering how many of those animals would have chosen death if given the choice, and how often it is simply a way to spare the own…

Always. Everything that pet owners do to their pets is driven by the owner's human feelings and not the pet's animal needs. Obviously, because we can't communicate with the pets and they can't tell us what we want. And we have total control over their lives so we do what we want. I'm personally particularly upset by the easy conviction with which most people neuter their pets. I can rant for hours on the ethics of th…

The harm of neutering and spaying needs to be balanced with the harm of having dramatically greater numbers of feral cats and dogs, whose lives are often what I will charitably describe as not enviable, and with the problems having large numbers of feral animals can cause to an area.

The alternative we in America have settled on right now is shelters which perform euthanasia on unwanted animals. I would love to know how communities that have banned these procedures deal with the issue.

Re: Daily pill can double survival time for deadliest cancer, trial shows

#48

Post by AustinDev »

roadnottaken wrote: post #33
siva7 wrote: post #31

> More than 90% of patients with the most common form of pancreatic cancer, pancreatic ductal adenocarcinoma (mPDAC), have a mutation in the Kras gene. So pancreatic cancer is basically a genetic disease for most patients instead of environmental?

No, the KRAS mutations are somatic (spontaneous), not inherited

So presumably something causes the spontaneous mutations?

Re: Daily pill can double survival time for deadliest cancer, trial shows

#49

Post by dredmorbius »

Retric wrote: post #35
dredmorbius wrote: post #30

Earlier quoted context omitted.

The pharmaceutical new drug development R&D market saw about $200 billion invested in 2025. https://hardmanandco.com/research/corporate-research/2025-ph... > Total VC tech investment in 2025 was $425 billion. https://news.crunchbase.com/venture/funding-data-third-large... >

You are excluding most government and charity funding into medical research. VC funding includes firms inside of the medical industry, but also companies operating across most of the economy. It’s not just IT, but food, solar, EV’s, rockets, etc. So, IMO these numbers are pretty reasonable.

I'm happy to see corrections with citations. I'd posted what information I could find.

I found your original dismissal without any documentation unsatisfactory, and wanted to quantify overall rather than specific-firm-instance funding. And you're still not providing any citations for your claims.

I suspect that the overall spend going into AI / adtech / digital media is disproportionately large relative to pharma spending. Particularly given the relative social benefits of each. I'd like to be able to make an evidence-based assessment rather than just a gut feel, however.

Clear breakouts of total investment spend by sector are hard to find, presumably much of the accurate information is paywalled. However from a Bain report I'd turned up earlier:

AI pulled in about half of all US venture funding in the fourth quarter, with investment spanning infrastructure, model training platforms, and AI-native developer tools.

https://www.bain.com/insights/global-venture-capital-outlook...>

Other significant sectors include, presumably in order, "robotics, AI, semiconductors, and Web3 sectors", and "Early-stage activity was strengthened by AI, robotics, defense tech, and biotech". All of which suggests that biotech is a small fraction of the overall total, and new drug discovery a smaller fraction of that.

Total US pharmaceutical industry R&D spend per a 2021 Congressional Budget Office report was $83 billion.

https://www.cbo.gov/publication/57126>

US federally-funded medical research largely occurs through the National Institutes of Health, which has an annual budget of $48 billion. I'd be quite surprised if state-level and other countries' spend doubled that. It increases my earlier figure by about 20%, which isn't nothing, but pales next to the venture tech investment. Again, that's all medical spending, not limited to new drug discovery.

https://www.nih.gov/about-nih/organization/budget>

As the previously-cited CBO report notes: "Much of that [NIH] funding has supported basic research (in genomics, molecular biology, and other life sciences) that has identified new disease mechanisms." So, not strictly new drug discovery, though not entirely unrelated either.

Most new drug discovery is likely not venture-backed, so considering my top-line $400 billion vs. $200 billion still seems to point to a roughly-appropriate comparison ratio. If anything, further research suggests the $200 billion value for pharma is probably high-side when it comes to drugs.

Re: Daily pill can double survival time for deadliest cancer, trial shows

#50

Post by dredmorbius »

matheist wrote: post #13
amluto wrote: post #4

Derek Lowe’s writeup is good: https://www.science.org/content/blog-post/progress-against-p...

> The company says that the drug was generally well tolerated, but that’s on the oncology scale. > ... > He’s been on daraxonrasib since early this year, and describes it this way: “. . .it’s a nasty drug. It causes crazy stuff like my body can’t grow skin and so I bleed all out of a whole bunch of parts of me that shouldn’t be bleeding” If you go to that link above, be prepared, because he also looks like he’s had a…

Hand-foot syndrome, a/k/a chemotherapy-induced acral erythema, is a similar condition, though there may be another I'm confusing with.

https://en.wikipedia.org/wiki/Chemotherapy-induced_acral_ery...>

I'd first run across this decades ago in the context of FDA drugs trials, in which adverse incidents were noted. My understanding at the time was that certain chemotherapies tended to interfere with skin regeneration, particularly in areas subject to high wearing (hands, feet, elbows), or rapid replacement (particularly mucous membranes, lips and mouth especially).

Not all chemotherapies are brutal, but some can be quite fiendish, and quality of life is a legitimate consideration when considering whether to proceed with treatment. Informed decisionmaking and consent in a context where expertise is rare and clinicians don't directly experience the adverse effects is difficult at best.

Post reply on HN