Skin cancer: Half of people surviving advanced melanoma

https://www.bbc.co.uk/news/health-49853878

by kieranmaine • 7 years ago

153 64 7 years ago

bbc.co.uk

breck2• 7 years ago

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• 7 years ago

Maybe this one?

https://www.nejm.org/doi/full/10.1056/NEJMoa1910836

breck2• 7 years ago

That's it, thanks!

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

stuartbman• 7 years ago

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• 7 years ago

Could you elaborate please?

yread• 7 years ago

Boosting immune system can cause all kinds of issues if one has an auto immune condition.

pflats2• 7 years ago

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.

011000112• 7 years ago

My buddy had bad GI symptoms(throwing up, diarrhea). He also lost his adrenals and thyroid. His thyroid may come back, but he'll be on pills for the rest of his life. IIRC, the treatment lasted about 2 years. He had the advantage of being a guitarist by trade who lived at home anyway. I'm not sure how someone with a normal life would have made it through it. He was the only patient who made it all the way through the trial. He also smoked cigarettes and marijuana, and had a opioid habit. That said, he still managed to keep hiking a couple times a week except on his roughest chemo weeks.

hestipod3• 7 years ago

I went through immunotherapy several years ago, for an iatrogenically induced issue which angers me more, and I think it permanently damaged me. I was quite sick for a while after and have never felt "the same" as before. I know that's vague and easily dismissed but it's as if the side effects of the treatment never went away. I also just spent months and a LOT of money on multiple biopsies apropos of the post's title, one of which got infected and created a whole other level of pain, stress, and cost, for a misdiagnoses. I never needed to be cut up and infected. This happened to me long ago in a more severe way with surgery as well that disabled me. Misdiagnosed by multiple doctors, spent tens of thousands, worse off. I would have had a much higher quality of life overall had I never gone to a doctor in this country. They have never gotten it right from small to big issues, and ruined my life in the process. I guess I need to just learn my lesson that the system can never be trusted here. But it's hard when you have pain or problems and want a solution. In my professional and personal experience the potential negative outcomes are always massively underplayed to patients. Medical errors/misdiagnoses are the THIRD leading cause of death in the USA. If I had been properly informed about any of the big issues I suffered I would have never agreed to "treatment" and better off for it.

jquery3• 7 years ago

All too common. I’m still dependent on a drug which was meant to be temporary but I was given such a high dose it permanently altered me. I’ve spent years tapering down and looking at another year to finally get off it, with no underlying issue anymore. Painfully slow, tedious, and maddening at times. I’m sorry you had to go through that.

erikpukinskis• 7 years ago

I guess I need to just learn my lesson that the system can never be trusted here.

I made a similar generalization about dentists a number of years back. I regret making that generalization now.

I wish I had instead decided “that one can’t be trusted, let me try another”.

clircle2• 7 years ago

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?

inetsee• 7 years ago

5 Year survival rate is one of the standard measures for the effectiveness of a medical treatment.

anovikov• 7 years ago

That's what always bugged me: after a 5-year survival, what is the typical probability of cancer ever returning? I.e. to what extent 5-year survival == "cure"?

_Microft2• 7 years ago

If you want a display that imo really hits home for some reason, see xkcd "Lanes". The uncertainty that patients are going through in the years after a cancer diagnosis/treatment must be brutal.

https://www.xkcd.com/931/

clircle2• 7 years ago

Oh I'm aware. I'm over 2 years since my diagnosis.

robbiep• 7 years ago

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

melling4• 7 years ago

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

toomuchtodo2• 7 years ago

How do we detect it earlier? And how do you scale that up?

akiselev• 7 years ago

We need tests with lower false positive rates. The problem with catching cancer early is confirming whether you actually have cancer or not. This most often requires invasive biopsies which exposes the patient to significant postop risks and the early detection tests' false positive rates mean that blanket tests of all patients would do far more harm than good. For example, mammograms have a false positive rate of something like 50% and complications happen in something like 30% of surgeries. Multiply that by every possible common cancer and you've got a no-win scenario.

All of our early detection tools are pretty terrible and we can't ethically test everyone for everything so it's all about educating the patients to take a proactive role.

legulere• 7 years ago

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• 7 years ago

But the question is: is that a real problem? Would it make preventive screening useless?

walshemj2• 7 years ago

Well it depends if you have an extra 25 yeas of life whats the price of that seeing your kids / grandkids grow up ?

astura5• 7 years ago

That was the conventional wisdom for years and it seems obviously true - catch cancer early before it spreads.

Yet when we actually study these things we find out early detection might not be desirable (but also sometimes is). It's complicated and there's a whole lot we don't know.

Also "most cancers" is almost certainly false, more like "some cancers." And at what cost?

https://fivethirtyeight.com/features/the-case-against-early-...

It’s hard to believe in overdiagnosis and overtreatment if you imagine that cancer behaves in a progressive manner: that is, that it arises from one haywire cell that replicates abnormally before inevitably spreading to other parts of the body, eventually killing the person. Let’s call this way of thinking the relentless progression model. In this model, every cancer cell is destined to spread and become lethal, and that’s how doctors have traditionally been taught to think of cancer’s progression.
Today, thanks to sophisticated cancer genetics and advances in tumor biology, we know that’s not always how it works. Cancer is not a single disease; it’s many. On one end of the spectrum lie cancers that become aggressive and invasive from the start, and on the other end are cancers that remain non-invasive and therefore harmless. Whether a single rogue cell replicates slowly and stays put or goes wild and spreads is determined by a variety of factors that scientists are still working to understand.
What’s clear is that cancers fall into a few general behavior patterns, which Welch and others have compared to animals that must be kept in the barnyard to prevent a deadly rampage. Papillary tumors are like turtles — they move very slowly and never pose an escape risk. They don’t need screening, because they will never cause trouble. Then there are rabbits, which are eager to hop away to other parts of the body, but can be confined if they’re found and fenced. These are the cancers that can be helped by early detection and treatment. Birds, on the other hand, are so flighty and quick that they can’t be confined. Screening makes no difference for bird cancers, because they’re so aggressive that they can’t be detected before they’ve begun their deadly course.
No cancer screening has ever eliminated the majority of cancer deaths. Instead, the best screening can do is reign in the rabbits. Birds remain unstoppable, and they’re the ones responsible for most cancer deaths. This is why, Welch says, three decades of mammography have failed to put a dent in the rate of women presenting with metastatic breast cancer upon their initial diagnosis.

https://www.wbur.org/commonhealth/2017/06/08/cancer-diagnosi...

Retric• 7 years ago

This is very age dependent. Slowly growing tumors are vastly more concerning on a 9 year old than a 95 year old.

mrosett• 7 years ago

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• 7 years ago

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.

aaavl2821• 7 years ago

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!

011000112• 7 years ago

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.

RickJWagner• 7 years ago

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.

civil_engineer• 7 years ago

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• 7 years ago

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.

tryitnow• 7 years ago

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.

Skin cancer: Half of people surviving advanced melanoma

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