"Adding abiraterone to hormone therapy at the start of treatment for prostate cancer improves survival by 37 per cent ..."
Not surprising that closing all the barn doors up-front, is more effective than closing them in sequence, as PSA increases. & I'd add an androgen receptor antagonist & a statin too.
-Patrick
PUBLIC RELEASE: 3-JUN-2017
Adding abiraterone to standard treatment improves prostate cancer survival by 40 percent.
Adding abiraterone to hormone therapy at the start of treatment for prostate cancer improves survival by 37 per cent, according to the results of one of the largest ever clinical trials for prostate cancer* presented at the 2017 ASCO Annual Meeting in Chicago and published in the New England Journal of Medicine today (Saturday).
The results from the Cancer Research UK-funded STAMPEDE** trial could change the standard of care for men with prostate cancer, making abiraterone a first-line treatment alongside hormone therapy.
This part of the STAMPEDE trial recruited around 1,900 patients.*** Half the men were treated with hormone therapy while the other half received hormone therapy and abiraterone. In men who were given abiraterone there was a 70 per cent reduction in disease progression.**** The drug is usually given to men with advanced prostate cancer that has spread and has stopped responding to standard to hormone therapy, but this study shows the added benefit to patients who are about to start long-term hormone therapy.
Professor Nicholas James, chief investigator of the Cancer Research UK-funded STAMPEDE trial from the University of Birmingham, said: "These are the most powerful results I've seen from a prostate cancer trial -- it's a once in a career feeling. This is one of the biggest reductions in death I've seen in any clinical trial for adult cancers.
"Abiraterone is already used to treat some men whose disease has spread but our results show many more could benefit. In addition to the improvements in survival and time without relapse, the drug reduced the rates of severe bone complications, a major problem in prostate cancer, by more than a half. I really hope these results can change clinical practice."
Alfred Samuels, 59, was diagnosed with advanced prostate cancer in January 2012 and joined the STAMPEDE trial two months later. He lives in Harrow with his partner and five children.
Alfred said: "It felt like my world fell apart overnight. The doctors explained that surgery wasn't an option for me because the cancer had spread beyond my prostate. "But my clinician suggested that the STAMPEDE trial might be a good option. As part of the trial, I started taking abiraterone four times a day and had a hormone injection every eight weeks. "During the first six months, tests showed that the treatment was working. I'm still on the trial, which I find reassuring and, fortunately, my cancer is being managed well."
Prostate cancer cells usually depend on testosterone to grow. Standard hormone therapy blocks the action of male sex hormones, halting the disease. Abiraterone goes further and shuts down the production of the hormones that fuel prostate cancer's growth.
Each year around 46,500 men are diagnosed with prostate cancer in the UK, and around 11,000 men die from the disease.
Sir Harpal Kumar, Cancer Research UK's chief executive, said: "These results could transform the treatment of prostate cancer.
Abiraterone can clearly help many more prostate cancer patients than was first thought.
"The STAMPEDE trial is changing the face of prostate cancer because the flexibility of the trial design means that we can investigate a number of different treatment options rapidly and in parallel, enabling scientists to get results much more quickly than they usually would. "Cancer Research UK scientists first discovered abiraterone and subsequently played a key role in its development, including funding the first clinical trials. This study adds to the importance of the drug."
The STAMPEDE trial is coordinated by the MRC Clinical Trials Unit at UCL and funded by Cancer Research UK. Previous results from the trial have already changed clinical practice - data released last year has led to docetaxel chemotherapy now being part of the standard of care for many men with prostate cancer. More data will come out in subsequent years, because of the innovative design of the trial. Professor James added: "We are so incredibly thankful to the patients and clinical staff who have agreed to take part in this study. With their generosity, scientists can carry out research that will help save lives."
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pjoshea13
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Thanks for the news. This is very encouraging. I do have some questions: One is how much additional time does it give you doing Abiraterone early vs later after you become CRPC? Also, how does this effect those of us who are just starting or partway through our Docetaxel chemo? Do we stop chemo and switch to Abiraterone, keep going on chemo until it's done, then start Abiraterone, or finish chemo then wait until CRPC before we start it?
Hoping to get some answers on these questions in the coming days.
But what does 37% increased survival & 70% reduction in disease progression mean?
About half the men in STAMPEDE had mets on entry, but the other half did not. Would help to know who did well.
Elsewhere: "The 3-year survival rate was 76% with standard therapy alone, but 83% with standard therapy plus abiraterone." i.e. a ~10% better chance of surviving 3 years.
{Will supposedly be published in the New England Journal of Medicine on Saturday 3 June, but I couldn't get to it this morning.}
I would expect the combination to achieve a longer overall survival. But the question I have: Is the overall survival longer between doing them together or doing one first and then the other. That's what matters.
Dr. Myers has said that in all cancers where a durable remission is achievable, the therapies involve multiple agents.
He argues that if the probability of any one drug failing is 10%, the probability of 3 drugs used together failing is 0.1 x 0.1 x 0.1 = 0.001. With such a low probability, one can expect a durable remission.
Of course, he is assuming that the drugs have independent targets. Zytiga & Xtandi are ADT add-ons. Myers' math might not hold up.
I was 56 when diagnosed & I'll use myself as an example. With a high probability of otherwise surviving another 25-30 years, I took a look at the mean-time to failure of available therapies. It was clear that once I needed to start Lupron, there wouldn't be many years left. I will be 70 in six months. Even with a met at L5 (radiated), I declined to start on Lupron.
Today we also have Zytiga & Xtandi & a few other things, but the sum of the mean-times to failure is going to come up short for a man who begins treatment in his 50's. So I hate to think that ADT + Zytiga might not be appreciably superior.
&, as I have said elsewhere, who knows how much survival can be enhanced by adding Metformin, a statin, nattokinase, eliminating metabolic syndrome symptoms, etc, etc, etc.
I'm hardly knowledgeable about this stuff, but I speculate that combination therapies have a key advantage over sequential therapies in that, in theory, they should bring the total tumor burden down lower than can be achieved by sequential therapies.
Dr. Myers' equation is based, as I understand it, on the theory that if 10% of the tumor population is resistant to each of 3 therapies, the overlap, then one therapy kills of 90%, the next, assuming only a random overlap of resistance, kills off 90% of the remainder, and the third kills of 90% of the remainder of that remainder. That leaves a very small tumor population that might even have trouble surviving or growing in the face of the body's regular immune systems.
However the actual effect could be even better. For example. It might be that some cells are partially resistant to one of the therapies and will survive one (be in the 10% survivors for that therapy) and also be partially resistant to another one. If applied sequentially, these cells survive both. But when applied together, the damage done by each therapy, when combined with damage done by the other, is enough to kill cells that could survive each of them applied separately. It's analogous to a man surviving a gunshot wound in a non-vital area, recovering, surviving another in another non-vital area, and so on, but dying of shock and blood loss if shot in all of the areas at the same time.
"It was clear that once I needed to start Lupron, there wouldn't be many years left." I started Lupron last month at 75 years young. What do you mean by many, 5years, 10 years, etc.
I know no one really knows, and we talking about averages. I delayed Lupron for 18 years. I just wanted to know your opinion.
I must have read hundreds of papers with boilerplate introductions stating that ADT fails in 18-24 months.
Occassionally, there would be a letter from a doctor saying that his patients did better. Perhaps because many had no mets?
Dr. Myers on his vblog posts on durable remission has said that with IADT, you had to aim for lengthy off periods, since you only have 2-3 cycles before CRPC. CRPC occurs because of ADT - it is defined by ADT failure. Why then rush into a treatment that induces a more aggressive form? But many men were rushed into it before Medicare stopped paying doctors $1,000 to give a Lupron shot.
I believe that with metastatic PCa, the majority fail within 18-24 months, but some fail much sooner & some later, but these are a small percentage.
From a 2010 study:
"After the first cycle, median time to CRPC was 2.9 years, and median time to death was 3.7 years."
The 18-24 months applies to Lupron as monotherapy. Obviously, adding Zytiga & an antiandrogen, etc, etc. should extend that - perhaps dramatically.
-Patrick
This appears to confirm something revolutionary. It is yet another reason I greatly value this forum. This, for me, is great to know for when (and if) that window opens. I have great and maybe even inordinate concern about windows of opportunity being missed.
A big IF may be whether insurances will cover drugs like this. Mine is [potentially sadly] Medicare. I wonder if they will consider it and cover it to be affordable for people of meager means. If so, I wonder how long it will take for the approval processes for this expanded use.
Connected to your great barn door analogy, I wonder if it was already a missed window of opportunity for me to decline hitting my presumably localized PCa (if that can truly be presumed) with ADT along with my first line treatment of IMRT. My RO helped in and concurred with the decision to decline based on severity of my mental health conditions (depression, anxiety, self-esteem challenges, etc). ADT side effect tolerance will obviously be a lesser concern when (and if) my life is more in the direct line of hit.
I have a friend diagnosed with mPCa last fall and I wonder about the implications of this for him. Hopefully he already uses this along with his ongoing Lupron.
Great point and advice, Rich. Thanks for the reminder. From what I am able to gather here, maybe there are advantages to declining/delaying ADT anyway, but you're so right that what's done is done.
Thanks for sharing this new information. It is exciting. I, too, took docetaxyl early, along with a Lupron, due to the results from the Stampede study that were published in 2015.
Someone asked about the implications of this 'new news' if you have already had early chemo. I have emailed my oncologist at MD Anderson today and will share her thoughts to this group when she responds next week.
This forum is truly a great source of information!
SATURDAY, June 3, 2017 -- Men with advanced prostate cancer might be able to avoid chemotherapy by taking an additional anti-testosterone pill along with standard hormone therapy, a pair of new clinical trials show.
The drug, abiraterone (Zytiga), lowered patients' risk of death by nearly 40 percent when added to standard androgen deprivation therapy, both studies found.
Abiraterone also appeared to more than double the average time it took for a man's prostate cancer to progress, one of the studies reports.
Doctors currently combine the chemotherapy drug docetaxel with hormone therapy to treat patients with advanced prostate cancer, where the cancer has spread to the bone or other parts of their body, the researchers said.
Abiraterone now offers a reasonable alternative to chemotherapy for these men, said Dr. Sumanta Kumar Pal, an expert with the American Society of Clinical Oncology and associate professor of medical oncology and therapeutics research for City of Hope in Duarte, Calif.
"At first glance it appears as though the benefit and survival seen with abiraterone mirrors or exceeds the benefit we've seen with chemotherapy," with less toxic side effects, Pal said.
The results of these trials are "pretty likely to change clinical practice overnight," said ASCO Chief Medical Officer Dr. Richard Schilsky. The studies are being presented this weekend at ASCO's annual meeting, in Chicago.
I'm very glad to see this because it matches my actual treatment experience - it's good to see some of the trial science catch up with what my doctor at MD Anderson and folks like Snuffy Myers knew intuitively several years ago. I was diagnosed in July 2012, at age 41, with a PSA of 80 and LN mets in my abdomen and peritoneal areas. My oncologist at diagnosis put me on Lupron and Casodex, and scheduled a follow up in 3 months. By September, after seeking a 2d opinion at MD Anderson, I was on Lupron, Casodex, Zytiga, Avodart and doing early course chemo with Taxotere (long before the CHAARTED study results). Once this strategy reduced my met burden, and brought my PSA under control, I had RALP to remove the original tumor. All of this provided about 18 months of control in my case, after which I experienced a relapse. I moved from Zytiga to Xtandi at that point, and have experienced a 42 month period of undetectable PSA and no met activity since. When my PSA went to undetectable on Xtandi, I also did Provenge, thinking that immunotherapy requires time to work, in combination with traditional PSA control strategies. I remain on Lupron, Xtandi, Avodart, Metformin, and a statin - but have fairly good quality of life, work full time, and am largely able to manage the side effects almost five years after diagnosis. I didn't seek out a specific doctor when I went for a 2d opinion but that decision remains the best one I made, because the subsequent oncologist was awesome - he intuitively understood that for a young guy like me, early use of Zytiga and chemo would extend my life.
This sound like a great breakthrough, My question is if one is not metastatic or only possibly lymph involvement but still stage 4 due to size & involvement of seminal vesicles & cancer excaping the capsule, is this indicated for helping my long term survival? PSA seems to have reached a nadir @ .74. Currently on Casodex & Eligard. My PSA has declined from 7.3 to .74 in 8 mos. I am Gleason 9 & 8 in all 8 samples.
Casodex, Eligard & Zytiga all target the androgen receptor, but in different ways. Treatment resistance is less likely when all three are used, rather than just Casodex & Eligard. The addition of Zytiga might prolong the efficacy of your current therapy.
Delaying until PSA begins to rise might be less beneficial.
There is no dispute about the additional survival benefit which is quite significant when Zytiga is used early in combination with ADT after having been proven by a long-drawn Trial - STAMPEDE. And also Zytiga can deal with the synthesis of androgen from all sources, not only the testicles. But can this combination deal with the most dangerous hormone insensitive cell types unless cytotoxic drugs are used to kill them? Doesn't this suggest early use of chemotherapy too has to be there in the multi-prong attack to deal with the real monster ( hormone refractive PCa cells ) ? Unless we are more worried about the side effects of chemo drugs than facing the monster!
We all should thank you for getting us this huge additional survival benefit of 37% ( News itself is as good as the real benefit! )
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Intermittent ADT/Zytiga? 
Digging into STAMPEDE data fir SBRT
High Gleason low PSA - quit ADT? 
ADT + Abi + Docetaxel for metastatic prostate cancer?
