
Skin cancer: Half of people surviving advanced melanoma - kieranmaine
https://www.bbc.co.uk/news/health-49853878
======
mrosett
This is amazing news. Many of the articles about "a cure for cancer" that get
posted here and elsewhere don't pan out, but this is the real deal. Obviously
the goal isn't 50% survival - it's 100% - but we've come a long way.

I was diagnosed with melanoma in 2010. At the time, the standard of care for
melanoma was remove it surgically... and then cross your fingers and hope it
doesn't come back.

During the 3 month interval between when I was first diagnosed and when we
learned that the cancer had spread, that changed. The first paper showing an
overall survival benefit for melanoma patients (by dosing them with
ipilimumab) was published in the NEJM in June 2010. Although ipilimumab
(marketed as Yervoy) wasn't approved by the FDA until the next spring, I was
able to get access to a very high dose of the drug through a clinical trial.

The trial was weird in a couple ways. First, I can get on clinicaltrials.gov,
pull up the results of my study, and calculate that if I'd been put in the
placebo arm of the trial, there's a 25% chance I wouldn't be here to write
these words. That's a strange thing to know.

Second, the side effects were really unusual and unpleasant. I didn't have to
endure the acute toxicity you get from chemotherapy, so that was a blessing.
On the other hand, immunotherapies (like both of the drugs referenced in this
study) mess with immune regulation mechanisms that apparently aren't supposed
to be messed with. My personal experience ranged from the mundane to the
miserable: fatigue, severe acne, absolutely excruciating eye infections, and
other stuff I won't get into here. I'm still dealing with some of these issues
almost a decade later, but the key point is that I'm here to deal with them!

Ipilimumab was the first step; James Allison recently won a Nobel prize for
discovering the protein that it targets. Nivolumab (marketed as Opdivo)
actually gives even better performance, so nivo is the standard and is
sometimes supplemented with Yervoy (or so I understand; I'm not a physician.)
I can only imagine what the side effects of the combination therapy are like.
Remarkably, both drugs were developed by Bristol-Myers Squibb.

~~~
PhantomGremlin
_if I 'd been put in the placebo arm of the trial, there's a 25% chance I
wouldn't be here to write these words_

I think you fared much much better than most. Maybe it's because you received
a very high dose of ipilimumab. The people in the article's trial (which I
assume wasn't your trial) were less fortunate. Specifically:

    
    
       The results showed:
    
          26% were still alive on ipilimumab alone
    

So 74% of the people in that trial are no longer here.

------
civil_engineer
I was diagnosed with stage 4 melanoma in Feb 2017. At my fourth treatment
(every three weeks) of pembrolizumab, my PET and CAT scans were clear. I
continued treatment for 12 months, and still get scanned every four months.
Still clear 3 weeks ago. My doctor says he now gets to use the c-word with
cancer patients. Minimal side effects for me. I wish for my cohorts that more
reliable treatments come soon.

~~~
simonsmithies
Similar response with pembrolizumab for my son, diagnosed with stage 4
melanoma in 2015. Side effects really quite trivial for him - more akin to
allergy/hay fever than what you see with other treatments. I understand pembro
is even better than the drugs mentioned in the article, both in terms of side
effects (less) and likelihood of actually working for a particular individual.

------
stuartbman
Its worth saying that some of the side effects of the newer immunotherapies
are bizarre, idiosyncratic, and unpleasant, in a different way from
chemotherapies. This is definitely good news, but patients undergoing
treatment for melanoma are still extremely complex to manage.

~~~
kaybe
Could you elaborate please?

~~~
pflats
As the article says, this immunotherapy essentially works by turning off some
of the immune system's "don't attack your own body" safeties. This frees the
immune system to attack the cancer (provided it can identify it).

One big advantage of immunotherapy is that the therapy causes a long-term
(permanent? I'm not sure anyone knows; the drugs are less than a decade old)
change to the immune system - the body continues to attack the cancer even
after the drug treatment has ceased.

If you put these two things together, however, you might see why the side
effects can be so bizarre. Your immune system might decide that the liver
looked at it funny one day, but then decide that the GI tract is actually the
real troublemaker a few days later. And since the immune system change
persists post-treatment, so do the side effects.

These side effects can (usually) be controlled with corticosteroids
(hydrocortisone/prednisone/etc.), which have an immunosuppressant effect. Of
course, long-term corticosteroid use has its own severe side effects (plus
severe dependency issues). And if you're suppressing the immune system, then
you're suppressing the mechanism that the immunotherapy uses to fight the
cancer in the first place. The treatment and the side effects are two sides of
the same coin.

~~~
klipt
> this immunotherapy essentially works by turning off some of the immune
> system's "don't attack your own body" safeties

That sounds like checkpoint inhibitor immunotherapy. Others like CAR-T may
have fewer side effects, since they're just augmenting your T cells with a
manufactured supply that is primed to attack a specific target.

CAR-T is a lot more expensive for now but over time such "precision"
immunotherapies may become mass produced and cheaper and we'll be able to make
the immune system do what we want with fewer side effects.

~~~
pflats
> That sounds like checkpoint inhibitor immunotherapy.

You are correct. That is because the article is about checkpoint inhibitor
immunotherapy (specifically yervoy/ipilimumab and opdivo/nivolumab).

------
melling
We could greatly increase the survival for most cancers if we could detect
them much earlier.

“ If it is caught in the early stages then the chances of survival are good,
but as the cancer becomes more aggressive and spreads throughout the body
(known as metastatic cancer) then survival plummets”

Craig Venter:

[https://youtu.be/iUqgTYbkHP8?t=15m37s](https://youtu.be/iUqgTYbkHP8?t=15m37s)

~~~
legulere
The negative side effect is that if you catch cancer in earlier stages you
also catch more cancers that would not reach later stages.

~~~
amelius
But the question is: is that a _real_ problem? Would it make preventive
screening useless?

~~~
jghn
Yes, it is a real problem. Cancer treatment is generally not a walk in the
park, and you'd be administering it to people who never would have otherwise
need it. Imagine having portions of your body removed and/or receiving brutal
treatment for no real purpose. Further, these tests have false positives and
even in the best case that could cause undue stress and strain.

It's been a while since I've been in the field, but at least as of several
years ago the oncologists I knew were starting to turn against heavy pushes
for early screening for these and similar reasons.

~~~
melling
Would you treat cancers that are caught 2-3 years earlier any differently?

Along with better early detection, aren’t we trying to increase the tests’
accuracy?

If we have 2-3 additional years to monitor and treat a cancer, we have more
options.

~~~
lukeschlather
My understanding is most people get cancer cells regularly. Possibly every
day. The immune system clears them out naturally. The question is how old is a
cancer before it becomes a threat worthy of analysis. Obviously one cell is
probably not interesting. I think there's evidence even cancers that are large
enough to be visible to the naked eye are not typically dangerous. If 99% are
harmless, what is the point in early detection? It's an expensive test and
expensive doctors visits to mitigate a 1% risk. It's interesting from a
research perspective to be sure, but not as a standard of care.

~~~
melling
It’s weird how people are worried about finding cancer too early. Many people
die early because they don’t detect it early enough.

My feeling is that we’ll be much better off it we detect at a very early stage
then learn to monitor it properly.

it almost sounds superstitious that people are afraid to find out sooner.

~~~
mekkkkkk
It's not about superstition or fear, it's about resource allocation and common
sense. Medical services are finite. Screening and continuous monitoring of
every potential tumor in everyone would be crazy time consuming and incredibly
wasteful. So let's not.

EDIT: Just to be clear, the idea of accurate early detection is of course a
good one. But as of today it is just not viable.

~~~
benibela
You could use an AI to identify and monitor skin cancer from photos/videos.

------
breck
> The findings of the study will be presented at the European Society for
> Medical Oncology meeting in Barcelona, Spain, and published in The New
> England Journal of Medicine.

Anyone have a link to a preprint? Can't find one anywhere. Hard to comment
without seeing the actual source.

~~~
oldgradstudent
Maybe this one?

[https://www.nejm.org/doi/full/10.1056/NEJMoa1910836](https://www.nejm.org/doi/full/10.1056/NEJMoa1910836)

~~~
breck
That's it, thanks!

For people without university or other access: [https://sci-
hub.tw/https://www.nejm.org/doi/full/10.1056/NEJ...](https://sci-
hub.tw/https://www.nejm.org/doi/full/10.1056/NEJMoa1910836)

------
clircle
The title says half of people survive advanced melanoma, but the article says
52% of patients live for 5 years. Are these medically the same?

~~~
robbiep
For reference, 6 years ago when I left medical school the average survival for
metastatic melanoma patients was 6 months.

------
aaavl2821
These drugs were originally developed by a company called Medarex, based on
academic research. Bristol Myers bought Medarex in 2009 I think.

From what I understand, Bristol Myers almost didn't develop the drugs. Back
then the idea of targeting the immune system to treat cancer wasn't a
mainstream idea. It's a very good thing they moved forward with them!

------
01100011
Yeah, my buddy survived it once, then it came back again as stage 4 and he
beat it using immune based therapy. Now his adrenals and thyroid are dead.
It's better than dying, but it's not free.

Edit: also, my buddy was the only guy in the study group who didn't drop out.
He just happened to be a massive pill-head(opiates), and smoked a ton of pot,
which probably helped get him through the side effects.

Immune therapies are worlds better than traditional chemo/rad, which often
ended up giving you an entirely different kind of cancer years later, but they
are not without side-effects.

------
tryitnow
I'm coming around to the view that treating cancer is mostly a resource
allocation issue.

I'd be willing to bet if we made even more aggressive investments in finding
treatments and cures, we'd be able to achieve both rapid incremental
improvements and a handful of breakthroughs with the net results being a
radical decline in suffering and deaths due to cancer (not to mention amazing
discoveries in science for the sake of science).

It's a shame we don't do this.

------
RickJWagner
Fantastic! I've had a few skin-cancer spots removed from my arms. (Failed to
use sunscreen in my younger years. Avoid this fate!)

I'm very glad to read this article.

