[HN Gopher] World-first experimental cancer treatment paves way ...
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       World-first experimental cancer treatment paves way for clinical
       trial
        
       Author : femto
       Score  : 200 points
       Date   : 2025-02-27 22:24 UTC (1 days ago)
        
 (HTM) web link (www.wehi.edu.au)
 (TXT) w3m dump (www.wehi.edu.au)
        
       | unstyledcontent wrote:
       | This is hopeful news for a really tragic cancer.
        
         | j45 wrote:
         | Truly hopeful.
        
       | Panzer04 wrote:
       | Presumably this is the Richard Scolyer case, if anyone was
       | curious.
       | 
       | A brief lookup indicates he could possibly be seeing recurrence;
       | hopefully that's not the case but this is something that many
       | people have said about his trial. We can't say for sure this
       | treatment is going to be broadly effective without more time and
       | experiments.
        
       | crispycas12 wrote:
       | It's neo-adjuvant (treat prior to surgery) with a three mAbs: Ipi
       | + Nivo, which is a well established combo of immunotherapeutics
       | for many solid tumors, rounded out with relatlimab which I'm less
       | familiar with (LAG-3 inhibition). Neoadjuvant use of
       | immunotherapies is established concept and is utilized in
       | clinical practice for non-small cell lung cancer and colon
       | cancer. This is the first time I've seen a use of 3
       | immunotherapies used at once: Ipi + Nivo isn't the most tolerable
       | treatment regimen. Other novel aspect is use of neoadjuvant
       | therapy in GBM.
        
         | trhway wrote:
         | Do they give immunotherapy before, after or instead of chemo?
         | Asking because I heard what it is after in some cases and that
         | puzzled me as chemo usually hits immune system.
        
           | femto wrote:
           | From what I read (in a book written by Scolyer), the
           | treatment didn't involve chemo. It was along the lines of: 1.
           | immunotherapy 2. Surgery to remove the bulk of the tumour. 3.
           | More immunotherapy 4. Radiation therapy 5. A course of
           | vaccine customised to the genome of the cancer
        
           | mft_ wrote:
           | That was a concern in the early days of development of anti
           | PD(L)-1 agents - that chemo and even steroids would harm the
           | T-cells you're trying to activate.
           | 
           | Yet there are settings where a deliberate combination of anti
           | PD-1 with chemotherapy is the standard of care. And there are
           | other types of immunotherapy where a combination with
           | chemotherapy is advantageous too.
        
           | mcbain wrote:
           | No chemo. The entire idea of this regime is to hit the tumour
           | with immuno to get the reaction. They want lots of tumour
           | cells and for it to be "treatment naive" - Richard hadn't
           | even had corticosteroids, which dampens immune.
           | 
           | Once they primed his system they excised as much as possible
           | and kept the immuno going while doing a course of radiation.
           | 
           | Profs Long and Scolyer work with melanoma where chemo is
           | rarely used these days.
        
         | jsperx wrote:
         | Don't mean to hijack this thread, but I don't think HN has DMs.
         | Read some of your comments and as a person with cancer would
         | love to pick your brain a little to develop my mental model
         | further (and of course wouldn't expect anything for free.) Drop
         | me a line at [my HN username] [at] nearby.org if open to
         | discussing more. Thanks!
        
       | sokols wrote:
       | This might be related with the case of Richard Scolyer, the
       | Australian pathologist diagnosed with Glioblastoma. He was
       | receiving some kind of experimental treatment for it.
        
         | crispycas12 wrote:
         | I believe he got just got either Ipilimumab and Nivolumab as a
         | combo therapy or Pembrolizumab. He's a researcher who focuses
         | on neo-adjuvant (use therapy before resection) therapy in
         | melanomas. It was a good gamble to try the same paradigm in
         | Glioblastomas
        
           | mcbain wrote:
           | https://www.nature.com/articles/s41591-025-03512-1
           | 
           | Ipi/nivo/relatlimab and then a peptide vaccine that they
           | haven't written up yet.
        
             | femto wrote:
             | Thanks for the link to the paper. I notice that the
             | abstract has a link to the page for the upcoming trial:
             | 
             | https://clinicaltrials.gov/study/NCT06816927
             | 
             | It will be interesting to follow its progress.
        
       | fragmede wrote:
       | It's not a generic novel treatment against any and all cancers,
       | as much as the headline would lead you to conclude.
        
         | crispycas12 wrote:
         | You're mostly correct but immunotherapies do work for a many
         | different type of cancer. The issue is differences in tumor
         | biology plays a major factor. The even bigger caveat is that
         | given a sufficient amount of tumor mutational burden (TMB),
         | immunotherapies are found to be effective for any solid tumor.
         | Granted most patients don't have the sky had TMBs needed for it
         | to be effective
        
         | adamredwoods wrote:
         | It's triple therapy, which most doctors won't do, which I think
         | is one of the future steps to stopping cancer. We should have
         | been looking at combination therapy a long time ago. Hopefully
         | this will get oncologists to push the envelope a bit more.
        
           | suzumer wrote:
           | I thought using multiple therapies for cancer was fairly
           | common, or are you referring specifically to immunotherapies?
        
       | kohbo wrote:
       | I'm not a fan of stuff in very early stages like this being
       | posted
        
         | 1970-01-01 wrote:
         | Agreed. Good but very early news isn't that interesting. It
         | needs at minimum a clinical trial.
        
         | Retric wrote:
         | A scheduled clinical trial is fairly late in the process.
         | 
         | It's a specific treatment being evaluated not just some
         | pathways discovered in rodents that looks promising.
        
         | femto wrote:
         | This one is an unusual case, as the clinical trial is coming
         | after the first patient (Scolyer) was treated. It's also
         | interesting due to its aspect of "Physician, heal thyself", as
         | Scolyer's own research formed the basis of his treatment.
         | Scolyer doesn't seem to have been directly involved in his
         | treatment, in that it was designed by his collaborator,
         | Georgina Long, and executed by another team.
        
         | Cthulhu_ wrote:
         | It's always cancer treatments and battery technology that gets
         | pushed to the top of tech news sites for some reason but it
         | never results in a "this problem is now fixed". Battery tech is
         | incremental at best and nowadays may suffer from its own scale,
         | that is, billions invested into battery factories set up to
         | churn out batteries using a certain technique, which
         | disincentivises new techniques.
         | 
         | But with batteries I like to think there's still plenty of
         | investor money and healthy competition, so a large scale solid
         | state battery plant may yet come to be.
        
       | JohnMD wrote:
       | I would like to see a clinical trial with patients who have Stage
       | 4 disease being treated with multiple immunotherapies, up to 5 or
       | 6 IV and oral immunotherapies. Why are we holding back in a
       | population with poor prognosis??
       | 
       | As far as legislation, we should pass "Right to Try" laws.
       | Allowing anyone with Stage 3 or 4 to pick an immunotherapy
       | regardless of whether it's been approved. We should never allow
       | hope to die!
        
         | s1artibartfast wrote:
         | Why can't you start a trial and do just that? Doctors have
         | discretion up to the practical limit of being sued by their
         | patients.
        
           | LadyCailin wrote:
           | Or their estate.
        
         | lumost wrote:
         | There is a bound on the degree to which terminal patients are
         | willing to be human guinea pigs, and a bound on which the data
         | is statistically useful to anyone.
         | 
         | I've read many reports of terminal patients who wish that they
         | hadn't wasted the last few months of their healthspan searching
         | for Hail Mary treatment options. If you were to ask yourself
         | what you would do with 1-3 months of healthy life left, would
         | you spend it in a hospital on chemo?
        
           | drysine wrote:
           | If I had a chance of beating cancer and extending my life by
           | a lot, I'd rather die fighting.
        
             | programjames wrote:
             | You're currently dying of the "being human" cancer. Are you
             | working on or donating to anti-aging research, or do you
             | prefer to do other things with your time? It just comes
             | down to your discount factor. Based on inflation, it's
             | typically about 0.95/year, so you would expect to care
             | about ~10% as much for things 50 years in the future. This
             | means if you had a ~10% better quality of life _not_
             | working on anti-aging, you 're guaranteed to be better off.
             | In reality, you should hedge your bets; if everyone spent
             | just a little time on the disease, we could cure "being
             | human". The same applies to dying fighting cancer. You
             | should be willing to do some experimental procedures, but
             | not if it eliminates your happiness for the rest of your
             | life.
        
               | somenameforme wrote:
               | One assumption people making such arguments implicitly
               | assume is that such things are possible, which is not a
               | given. It could well be that you could have infinite
               | money, a billion scientists, and make no progress
               | whatsoever. And I'm only referring to cancer there. Anti-
               | aging seems even less likely.
               | 
               | I think there's a lot of cognitive dissonance on this
               | topic from people like Ray Kurzweil. The overwhelming
               | majority of increases in life expectancy over the past
               | millennia have come from reductions in childhood
               | mortality. It's not like people in the past just hit 40
               | years old and randomly keeled over. But rather people
               | were quite unlikely to make it out of childhood. If one
               | person dies in childhood and the other at 80, you have a
               | life expectancy of 40 years old but it's rather
               | misleading! In reality the average life expectancy (for
               | those that made it out of childhood) has remained pretty
               | similar for millennia - around 70 years. [1]
               | 
               | So for instance the Founding Fathers died at an average
               | age of 72. John Adams lived to 90, and Sam
               | Adams/Jay/Franklin/Madison died in their 80s. The only
               | two who died before their 60s were Hamilton, who was
               | killed in a duel, and Hancock, who'd had poor health
               | throughout most of his life. This is a nice sample
               | because you had Founding Fathers as young as 18 (Monroe)
               | when the Declaration of Independence was signed, so we're
               | certainly not seeing a surviorship bias. They were
               | certainly wealthier than average, but all the wealth in
               | the world doesn't matter when state of the art healthcare
               | was doing things like treating infections by bloodletting
               | (including by leeches) to get rid of 'bad blood' or
               | 'balance the 4 humors.'
               | 
               | [1] - https://aeon.co/ideas/think-everyone-died-young-in-
               | ancient-s...
        
               | kelnos wrote:
               | Not arguing against your general point that post-
               | childhood life expectancy has always been fairly high,
               | but I don't think rich aristocrats make for a "nice
               | sample" when talking about longevity.
        
               | somenameforme wrote:
               | Most of the logic about endless life expectancy take
               | improvement in healthcare as the fundamental driving
               | factor. And in the past, the wealthy were no better off
               | than the impoverished here because you couldn't buy that
               | which didn't exist. Germ theory didn't exist, let alone
               | antibiotics, even hand washing as a thing before surgery
               | didn't yet exist. And what I was alluding to in my
               | comment was what happened to George Washington. He died
               | at a relatively early age of 67 of a throat infection, or
               | of the 5 pints of blood that was taken from him to 'cure'
               | that infection leaving portraits of him on his death bed
               | as being white as a ghost.
        
               | cogman10 wrote:
               | > the wealthy were no better off than the impoverished
               | here
               | 
               | Eh, in some ways but not all ways.
               | 
               | The wealthy, for example, were much more likely to
               | receive proper levels of nutrition. They could afford to
               | eat well balanced meals.
               | 
               | If you are poor, you're living off of whatever you can
               | scrounge up or grow.
        
               | askonomm wrote:
               | That's why I always think that the _mean_ life expectancy
               | is a much more useful metric than _average_. Not sure why
               | everybody reports the average everywhere. I have the same
               | exact thought when it comes to salaries. Governments and
               | the like always publish the _average_, which tells very
               | little to the regular person. If anything, it would tell
               | the regular person that they must really be very badly
               | off if most make more than them, having a negative
               | effect. Perhaps that's the desired outcome?
        
               | Earw0rm wrote:
               | Mean _is_ average. You perhaps mean median?
               | 
               | Even then though, in e.g. Victorian times, the median
               | (50th percentile) gets skewed by horrendously high infant
               | mortality.
               | 
               | Looking at the 75th or 80th percentile, or the life
               | expectancy for an 18 year old, is a better measure. High
               | scores for the 75th can mask deaths due to inequality to
               | some extent, but because wealth distributions are _so_
               | skewed at the top, the 75th percentile typically looks
               | more like an average/poor person than a rich person.
        
               | askonomm wrote:
               | I did mean median yes, my bad. Alright, that makes sense
               | indeed.
        
               | somenameforme wrote:
               | Yeah, even the median life expectancy in the past would
               | be getting awful close to something like 2 years old. [1]
               | Again running with the Founding Fathers as an interesting
               | example, Sam Adams lived until he was 82 and was one of
               | 12 children. Yet of all those brothers/sisters, only 3
               | lived past the age of 3.
               | 
               | It's this context that I think explains things like
               | infant 'exposure' in various cultures over time that we
               | can't even imagine today - parents simply leaving their
               | child out to the wilds, essentially to die - while
               | retaining that cognitive dissonance that perhaps he might
               | be found and raised by somebody, as was a frequent
               | component in the hero legends, such as with Theseus and
               | Perseus.
               | 
               | [1] - https://ourworldindata.org/child-mortality-in-the-
               | past
        
               | wahern wrote:
               | > Not sure why everybody reports the average everywhere.
               | 
               | Because that's the modern definition of life expectancy:
               | the average (mean). Probably because the primary driver
               | behind the production of actuarial tables has always been
               | for insurance, annuities, and similar purposes. For
               | calculating costs and valuations the mean is often a
               | better measure because the distribution of deaths isn't
               | normal. Though in modern actuarial tables you'll often
               | find both.
               | 
               | I would assume popular literature quotes expectancy
               | figures from birth because that's the easiest thing to do
               | when you're just trying to give a single simple figure.
               | But actuarial tables have always been just that--tables.
               | Given a person at age X, what's their life expectancy.
               | The first row will be from birth, but people with money
               | on the line have always understood that number is mostly
               | irrelevant. Here's an actuarial table from the 3rd
               | century which was built for calculating annuities:
               | https://en.wikipedia.org/wiki/Ulpian%27s_life_table
               | Interestingly that table seems to use median life
               | expectancy.
               | 
               | Actuarial science was a significant driver in the
               | development of modern statistics and mathematics,
               | especially as the market for financial products exploded
               | over the past several centuries. The tables and models
               | for life expectancy from 150 years ago were startlingly
               | accurate, even in their forecasts of changing life
               | expectancies. When Social Security was passed in the
               | 1930s the models for how life expectancies would change,
               | both from infancy and across all the age brackets, were
               | spot on with actual changes up to the 1990s.
        
               | programjames wrote:
               | I seem to be much more confident that technology could
               | solve the aging problem. Two routes come to mind:
               | 
               | 1. We can already splice up DNA with decent accuracy, so
               | it's just a matter of finding _what_ DNA to splice in
               | /out to have the desired effects, and then a method to
               | apply this to every cell.
               | 
               | 2. We're close to being able to disassemble someone's
               | nerves and simulate them with a very high accuracy. So,
               | at the very least we could give people new robot bodies.
               | 
               | Now, it's true that even the wealthiest people in the
               | world several hundred years ago had no hope to get either
               | of these done. But it seems entirely plausible that if
               | everyone came together to work on this _now_ , it could
               | be solved in a few decades. I think it isn't happening
               | because (1) people's discount factors aren't high enough
               | to throw everything to their future; (2) the wealthiest
               | people are older, and have the least chance of success;
               | (3) it's a coordination problem that most people aren't
               | even aware they can coordinate on; (4) a significant
               | number of people don't even think it's a problem (because
               | of the stories their ancestors told about death maybe not
               | being the end). The last two are solvable, but the first
               | are just mismatched preferences that you can't really get
               | around.
        
               | drysine wrote:
               | >donating to anti-aging research
               | 
               | Not as much as I should've. You've made a good point,
               | thanks.
        
             | jajko wrote:
             | I would not. I would focus on family and friends, leaving
             | as little mess to work through for them after my passing
             | and making the best out of remaining days. Quality >
             | quantity for me, always.
        
               | kelnos wrote:
               | There are always thresholds, though.
               | 
               | Would you accept a 10% decrease in the quality of your
               | life in exchange for an extra year? I probably would. I
               | probably still would if that was a 20% decrease. But I
               | probably wouldn't go for that extra year if I had to
               | accept a 90% decrease in the quality of my life.
               | 
               | The threshold is a personal decision. There are no right
               | or wrong answers. We should even indulge someone who
               | _would_ accept that 90% decrease for an extra year. That
               | should be their choice, and even if I wouldn 't make it
               | myself, that's neither here nor there.
        
               | rsynnott wrote:
               | > Would you accept a 10% decrease in the quality of your
               | life in exchange for an extra year? I probably would. I
               | probably still would if that was a 20% decrease. But I
               | probably wouldn't go for that extra year if I had to
               | accept a 90% decrease in the quality of my life.
               | 
               | The context is _clinical trials_, tho, so that's not
               | generally what's on offer.
        
             | agumonkey wrote:
             | I would believe that for many people, simply having a
             | chance at fighting would improve the odds.
        
           | deadbabe wrote:
           | You are not just fighting for yourself, you are fighting for
           | all future generations by helping to contribute toward
           | finding a cure, even if you don't benefit it from it. It is a
           | noble cause, like going to war to defend your country.
           | 
           | If you only want to contribute toward things if they benefit
           | you, then the real cancer is you.
        
             | llamaimperative wrote:
             | This is extremely goofy. No one is obligated to try
             | experimental drugs to benefit other people. And I work in
             | clinical trials!
             | 
             | It is heroic to volunteer oneself into a clinical trial.
             | 
             | In fact, if you feel so strongly about it: you can go do so
             | literally right now. I'm happy to help facilitate.
        
           | 1270018080 wrote:
           | Of course you would make different choices if you could
           | predict the future. But if I only have 1-3 months to live, I
           | am going for Hail Mary treatment options to try to extend
           | that (because I can't predict the future).
        
           | cancerhacker wrote:
           | I'm no longer NED from Stage IV colon cancer (first DX 2014),
           | and now it's returned and inoperable. I was given an option
           | to add Cetuximab which I'd had previously- but the side
           | effects from that were so bad for me that it absolutely isn't
           | worth it to me to add a few months, but live in misery.
        
         | robbiep wrote:
         | Whilst this would be great, can I just temper this with a
         | little understanding of how significant some of the side
         | effects of the immunotherapies can be. There are significant
         | limits on how much you can stress an already significantly
         | stressed body and immunotherapy side effects can be WILD
        
       | dumbledoren wrote:
       | It cant be coincidental that this news with a misleading headline
       | is being pushed right at the time when a revolutionary Chinese
       | drug changed the landscape.
        
         | aj_icracked wrote:
         | Out of curiosity, and I'm living under a rock.. which one?
        
         | Nevermark wrote:
         | > It cant be coincidental
         | 
         | And yet coincidences happen. So of course it can be.
         | 
         | I suggest avoiding starting any sentences you intend to be
         | credible with that phrase. And avoid starting any sequence of
         | reasoning you wish to have validity with that type of thinking.
        
       | tanujsh979 wrote:
       | This could be groundbreaking I guess! :)
        
       | catoc wrote:
       | How is this the "first experimental cancer treatment" ?
       | 
       | It's not. Of course.
       | 
       | It may be the first triple immunotherapy (3 checkpoint
       | inhibitors), given in a neo-adjuvant setting, in glioblastoma.
       | 
       | Still cool, less catchy
       | 
       | (Or maybe I don't understand "world-first" ?)
        
         | cryptopian wrote:
         | The term "world-first" in this context means that this is the
         | first specific cancer treatment of this type:
         | 
         | > It is the first documented use of neoadjuvant triple
         | immunotherapy in glioblastoma
         | 
         | If the headline read "world's first" then it would imply what
         | you understood
        
           | skybrian wrote:
           | We love to debate headlines, don't we? But along those lines,
           | it seems like they could just say it's "new" and that would
           | be good enough; a headline doesn't need to be any more
           | specific.
        
       | baggachipz wrote:
       | This is fantastic news, glioma treatment progress was stagnant
       | for a long time and is finally starting to pick up steam.
        
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