Greetings! Looking to network, educate on the path I took, and learn from the rest of you who've been in the trenches. I got tired of standard of care (diagnosed 3/14, surgery 4/14 (gleason 9, 85% of prostate with tumor, seminal vesicle invasion - just a mess), pelvic bone mets found 6/14 (6 week post-op PSA of 3.76...crazy), started eligard and 6 rounds of docetaxel 7/14 thinking I was still hormone sensitive, bone biopsy in 1/15 affirmed that small population of tumor cells still growing - so mCRPC I guess). In Jan '15 I pushed for genomic sequencing to find molecular abnormalities that fueled my advanced aggressive prostate cancer. Sequencing showed hyperactivity along Pi3k signaling pathway (P53, pi3k and PTEN loss) and i used that data to get on a pi3k inhibitor clinical trial drug. 14 months later cancer still shut down (progression free). I'm a big fan of unlocking the molecular alterations and going after it with targeted drugs. If my cancer starts growing again, I'll just sequence the met (blood biopsy most likely) and go after the new culprit. Happy to answer any questions folks have. I'm very curious about immunotherapy and if guys are on Pembro or Ipi and have had success.
My path to Precision Medicine - Advanced Prostate...
My path to Precision Medicine
Very interesting information Bryce. a whole lot to have happen all at once with the aggressiveness. So glad you have the smarts to do what you are doing.
keep up the great work!
most sincere,
Jackie
Well that's very nice of you to say that. I had to learn a lot quickly. Got deep in genomics and I think answers exist there. But as you know we can never get complacent. It's a blocking and tackling game and the goal is to stay in front of it. Ton's of helpful folks on this site though, incredible information. I'm glad I found it. Best of luck to you and let's stay in touch
I have been reading some of the link that you added here.... this is quite amazing. I haven't heard others speak of it but did not know where to find it to read about it. I will be doing more reading. is it very difficult to get started. How does one know which test to pick? I would think you would want to test everything but that's just my personality LOL. more is better bigger is sometimes better LOL. So much to choose from. it would be interesting to do for your own health not just 1 with prostate cancer. yes definitely keep us posted as I will also. Kit Jackie
Jackie, what part of the country do you live? I can advise you better based on that.
Pennsylvania Bryce
www1.pennmedicine.org/perso...
check this out!
Thanks Bryce, I have stage 4 and with a gleason 9 back in May 09, robotic in 10/09 and then 3/10/ 09 radiation treatment. 8/10 PSA started rising went on ADT and it went into my spine, in 12/14 bone mets healed (not sure how) with all the stuff I was on supps & meds. Anyway I am now on Zytiga and the PSA is on the rise again up to 16. I am having another CT scan and Bone scan 6/13. So I feel good and feel blessed to go this far. I appreciate your post but lost you when you started talking about genomics? Thanks
Bill in Powell Ohio
Hi Bill. Genomics is what provides the keys to the 'Precision medicine' car. Precision medicine is the theme of ASCO this year, it's a big deal.
theguardian.com/science/201...
Think of genomics and tools like next generation sequencing as the diagnostic that can dig all the way to the source of your cancer deep in the DNA to pinpoint what is fueling it. We're all different, so why should we all be on the same treatments? Standard of care for PCa today focuses a lot on inhibiting androgen receptor and chemo (shotgun approach). But what if your cancer is using a different pathway to grow? Mine was. It's nice to know that because then you can target it with something that isn't as toxic as chemo. This help?
Thanks Bryce. Yes it does. I am being treated here at the James in Columbus Ohio, You would think they would be familiar with it. I pray you will continue to stay in remission. Thanks again. Bill
My History is posted elsewhere on this site. Can anyone provide a link for genetic testing in Massachusetts. I have been on Xtandi for 30 months, with PSA rising for past 12 months from nadir (0.07) to 0.75. Bone Scan this week revealed bone Mets resuming growth in L1 and new site at L11. I am ready for genetic testing. Thanks and Good Luck to all
DFCI (Dana Farber) I believe sequences everybody with advanced cancer that walks in the door, and if they don't proactively do this then you just need to ask and they will. They have a huge effort going on in this space.
dana-farber.org/Research/In...
UMass as well:
umb.edu/news/detail/umass_b...
I have asked numerous times for a genetic profile to be performed, but have been told my insurance will not pay. Though I am ready to pay for myself. The disappointing thing is every where you read they do a genomic analysis for $1000 now, but they keep telling me it is at least $3000. But at this point it is a small price to pay.
This is my situation too, I would like to get sequenced so we know how to attack things in the future, but they say that I'm not "bad enough" yet. I had surgery a year ago with seminal and lymph node invasion wo we know that it's out there somewhere, but at the moment my PSA is 0.05 so they tell me I'm not in line for any additional treatments beyond Lupron at this time. I hate sitting here waiting for the other shoe to drop before we take additional steps, but i suppose the insurance company doesn't want to pay for something that there is a slim chance I won't need. It's frustrating.
Bryce
Glad to hear of your success. What inhibitor are you taking? Where are you being treated.
I have been sequenced with no actionable mutations. Although I did give Olaparib a shot anyway.
I am interested to find out how you are able to get the inhibitor. Is your insurance covering the cost? Clinical trial if so which one.
Thanks
Bill Manning
Hi Bill. So my sequencing data revealed driver mutations along the Pi3k signaling pathway (with a P53 mutation along with tumor suppressor gene PTEN loss which really left me vulnerable with an open freeway on this pathway for proliferation). So I found a phase 1 drug that inhibits both pi3k and downstream MTOR, it was nice to have a dual inhibitor actually - better coverage I feel. There's at least ten pi3k inhibitor drugs in development right now. It's impossible to really know which one will be the best or most effective - but I just went for it and got onto any trial testing these drugs as I could. Phase 1 trials can be nerve racking because as you all know phase 1 means you're the first humans ever to take the particular drug at that particular dose. It's truly Lewis and Clark (reference from my pacific northwest location). I could write a whole different post just on being in a phase 1 trial and what that is like.
BTW, I was the only prostate guy in my cohort. And I'm the only one left after 14 months (everybody else progressed). Why? Nobody else was a direct match for the drug. I was the only person that came in with sequencing data showing that I was a direct match. Everyone else were just advanced cancer patients in the LA area willing to try anything, spinning the wheel of trial and error treatments. My trial location is Cedars Sinai.
I think it's great that you got access to Olaparib. But I believe folks that respond best to this will have DNA Repair pathway mutations (i.e. BRCA1, BRCA2) making them the most suitable candidates for PARP inhibitors.
Lastly, there aren't that many actionable mutations in the primary tumor, but there are in the metastatic tumors. From a genomics perspective, it's like a different cancer entirely. And if your primary tumor is what you do the sequencing against, it's not going to give you the right data if you now have metastatic disease and have been on multiple drugs post RP. You need to sequence the met (needle biopsy or blood biopsy which is much easier)
Does this make sense? Helpful?
Yes very helpful. My sequenced tumor was not from primary tumor but from lymph nodes from a surgical procedure after I was castrate resistant in 2013. I had my liver tumor biopsied last year as well but while the biopsy was positive for prostate cancer the sample was insufficient size for genetic testing. Dx'd at 49 10 years ago. I have done all the prostate cancer treatments over the past 10 years including 3 different chemotherapy regimes. Now on an oral chemotherapy drug.
Great to hear of your success and I hope and pray it continues. You have done a really good job of looking for a solution.
Thanks for the information.
Bill
Well thank you! A lot of fortunate luck on my part as well. I get inspired seeing you guys fight this - 10 years in your case and going strong - it's awesome and gives me hope too. I'm a newbie at this being diagnosed just in March 2014.
You just keep on talking Bryce.......
We'll try to keep up. So far we're with you understanding..... extremely interesting.
This is remarkable and shows how far we have to go:
"BTW, I was the only prostate guy in my cohort. And I'm the only one left after 14 months (everybody else progressed). Why? Nobody else was a direct match for the drug. I was the only person that came in with sequencing data showing that I was a direct match. Everyone else were just advanced cancer patients in the LA area willing to try anything, spinning the wheel of trial and error treatments. My trial location is Cedars Sinai."
Hello Bryce.
I'm curious about your science background. There aren't a lot of folks who know what p53, PTEN, DNA repair, and even biochemical pathways are, and learning about them is not a quick or trivial task. Are you a professional in biology or chemistry? Did you have an interest in molecular biology before starting your cancer journey?
You've certainly made outstanding use of your knowledge. I wish every medical oncologist were as smart about this stuff as you have been.
Thanks.
Alan
Hi Alan. No science background at all:-). Just the crash course I put myself through last 18 months. Took the most minimal amount of science possible in both HS and college, thought it would be too hard:-). I suppose I never saw the relevance when I was younger. Small town Montana kid. Biz major in college. But as a young adult found out that I actually liked a mental challenge (learned Japanese, got into high tech, been at it ~20 years.) Been at Intel over a decade, data center biz dealing with big data analytics, cloud computing - enjoyed it but I wouldn't say I was passionate about it. I knew Intel had a 'health and life sciences' group but didn't have any interest in that specific segment. Then I got advanced PCa and everything changed. Now this healthcare group became the only group that interested me after being out on medical leave. I got in, and learned about the 'life sciences' portion of that business. It was fascinating and I quickly saw how I might be able to apply this to my own cancer battle. That's when it became personal for me. When I applied genomics and precision medicine to my own case and it worked, it basically became like a 'religion' for me. Now that I've gone 14 months and it's still working, I thought it was time to start engaging with my fellow advanced PCa brothers and share what I learned, especially with folks who are running out of options and could benefit from a 'plan b'.
It's really chicken or egg. Unless more advanced cancer patients learn about this and demand genetic testing along with the precision medicine therapies that align to the genetic makeup of the patient, none of this will become standard of care. I could go on and on, but I won't. I'll stop. But it's really frustrating - this inefficient market today. (i.e. patients don't know about genomics so they don't ask their doctors to give them the tests, doctors don't offer the sequencing tests or 'targeted drugs' because it's not standard of care, drug companies who make these 'targeted' drugs can't find patients with genomic data to even give them too, insurance won't pay for sequencing tests because the drugs that map into it are not standard of care.)
Hello Bryce,
You are to be congratulated for your quick absorption of the molecular biology of genes.
I suspect that you also had a little luck on your side here. As I understand it, scientists have found correlations between cancer and genetic characteristics for some cancers and not for others. Until very recently, prostate cancer has been in the "not for others" category, although there are some mutations that can affect any solid tumor, including prostate cancer. There just hasn't been that much known about genetics and cancer until recently, and even now I suspect the part that we know is way, way smaller than the part that remains to be discovered.
However, even where a genetic anomaly is understood, the development of a safe and effective method of taking advantage of that in treatment is a long, multi-year process, first of very basic research, then of very difficult applied research, and then of clinical trials for safety and efficacy. For example, a scientist might discover that a a particular point mutation in a gene that codes for a DNA repair protein is causing that protein to be inactive, increasing the rate of mutation in tumors. But knowing that and knowing what to do about it are radically different things. There's no way to send a mechanic into the nucleus of each of a million tumor cells to repair the mutation and some really imaginative research together with a really deep understanding of biochemistry and molecular biology is needed to come up with some way to use the information gained about the mutation to do anything to treat the cancer. So I think you won the lottery on that one (if anyone with cancer can be said to have won the lottery.)
I'm not disagreeing with your enthusiasm for precision medicine. I think it has a very bright future. But as things stand now, I suspect that the majority of PCa patients who go down that road won't (yet) find much help.
Still, you did win and if you hadn't put out the effort to understand all this and try to take advantage of it, you'd be in much worse shape. So while I think you were lucky I also see that you made some of your own luck.
Well done!
Alan
This is very interesting and takes us to the specific mutation of our own ca. at the cell level.
Exactly. I agree, it's fascinating. We're all unique and should be treated that way honestly. This 'one size fits all' feels like trial and error medicine and it doesn't have to be. I think standard of care is great if you have early PCa and doctors can cut or burn it out of us. But for us with advanced metastatic PCa, scientists already know that our cancers are not all the same. Why is it that some guys get a ton of mileage out of a drug and the next guy gets zero mileage out of the same drug? Because we're all different. Answer to those differences is in our unique DNA.
Hi Bryce, I may have just missed it, but what was the specific inhibitor drug used in your specific clinical trial? Many thanks for the great input here!
I'm on a drug that has no name but has a number. It's VS-5584. Phase 1 clinical trial. My cohort got the highest or second highest dose before they capped it. I got really lucky. I'm hoping that I get a lot more mileage out of it, but I'm also grateful to have gotten 14 months already. I am nervous that if my cancer builds up resistance to this drug and starts using a different pathway to grow, that the new pathway may not be as treatable as the Pi3k/Mtor pathway was (i.e Today's inhibitors don't stop cancer on the RAS/RAF/MEK/ERK pathway as well for example). But every year new advances are made and I just need to keep blocking and tackling to keep it contained. I'll deal with resistance when it happens:-).
Another tip, besides the oncologists you already know, make friends with pathologists. They are experts in this space:-).
Bryce, I have the same genomic defects : Pi3k signaling pathway (P53, pi3k and PTEN loss). I started a Phase 1 clinical trial this week with AZ-8186. I am looking for similar positive results. Good Luck!
Do you discover these genetic defects from the standard genetic testing that they do for someone with advanced PCx? Or, is it a more detailed genetic test?
Here is a link to the trial Bryce took part in:
clinicaltrials.gov/ct2/show...
I read:
Recruitment Status : Terminated (Lack of recruitment and the company's decision to de-prioritize 5584 development)
Do you discover these genetic defects from the standard genetic testing that they do for someone with advanced PCx? Or, is it a more detailed genetic test?
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