Emerging trends in the management of advanced prostate cancer - Drugs In Context - 2021 Mar 15

[cujoe]

An excellent summary/overview of the current treatments for metastatic hormone-naive/sensitive prostate cancer (mHSPC) management with tables of completed and current recruiting clinical trials. This is a tool all advanced hormone-sensitive PCa patients should study carefully and review with their treatment oncologists.

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Volume matters and intensification is needed: emerging trends in the management of advanced prostate cancer

Iris Y Sheng - Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA.

Pedro Barata - Department of Internal Medicine, Section of Hematology Oncology, Tulane University Medical School, New Orleans, LA, USA.

Raafat Alameddine - Department of Hematology Oncology, University Hospital Cleveland Medical Center, Cleveland, OH, USA.

Jorge A Garcia - Department of Hematology Oncology, University Hospital Cleveland Medical Center, Cleveland, OH, USA

Abstract: Significant changes in the management of patients with de novo metastatic prostate cancer have led to the use of novel oral agents and docetaxel-based chemotherapy earlier in the natural history of their disease. Our main challenge is the lack of prospective randomized data comparing these regimens. It is clear that treatment intensification is needed. Yet, the heterogeneity of this patient population coupled with the lack of understanding of the specific biology for a given individual makes treatment selection challenging. The aim of this narrative review is to discuss the importance of defining advanced disease by volume, the necessity for treatment intensification, and the current and future landscape of metastatic hormone-sensitive prostate cancer management.

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Full PDF of research paper is here:

drugsincontext.com/wp-conte...

Be Safe & Stay Well - K9 terror

[NPfisherman]

K9 Terror,

A great article... Bob Dylan was right...."the times they are a changing..." One of the authors, Dr Garcia at Cleveland Clinic works with my MO, and they are keeping track of about 80 oligometastatic patients that followed the route that I and many others have followed with SBRT plus ADT with Zytiga and prednisone. My MO thinks that people that reach "undetectable" state doing that treatment will have long remissions/vacations.

The use of genetic testing will provide targeted therapy for patients and prolong OS. The current guess is that about 1/3rd of Stage 4 PCa patients will survive 5 years. That is up from the 20% prediction by ACS just 2 years ago... I figure we will be around 50% or more in 2 years with the addition of Lu-177 and other therapies.

I will stick with my prediction of chronic disease state within 5 years...

Fish

[StayingOptimistic in reply to NPfisherman]

But I heard from dr. Sholtz and others that some patients living more than 10 or even 15 years, very confusing subject.

[NPfisherman in reply to StayingOptimistic]

Indeed, there are people that live longer but Stage 4 patients --people with metastatic disease do not all live 10-15 years... this is evolving... will there be a time when this is true?? I think so... look at American Cancer Society statistics... as you read the forums, you will see loved ones post about individuals dying within 2 or 3 years... saddening...

Fish

[Shooter1 in reply to NPfisherman]

Stage 4 and 4 years in.... I have seen people come in new and depart with what looks like a less aggressive and less wide spread aPca than I have... Once again, we are all different and the drugs will effect each of us differently. Wish you all (and me) a good run and long comfortable life...

[NPfisherman in reply to Shooter1]

Congratulations on 4 years... you are correct...each person has his own version....mutations, locations, gleason scores and variations do make a difference... We are each a variation in the disease scheme of PCa...

All the best to you and us all....

Fish

[StayingOptimistic in reply to NPfisherman]

I heard dr said that some men with metastatic disease live 10-15 or more in his clinics.

[NPfisherman in reply to StayingOptimistic]

Here is information from Johns Hopkins-- please note Stage IV--metastatic prostate cancer 5 year survival rate of 28%--see below:

hopkinsmedicine.org/health/...

The reality is no one knows how the disease course will go for each patient...I reviewed your profile....not sure why you were not started on abiraterone plus ADT as per the STAMPEDE trial for survival benefit, even if only doing it for a year (IADT)....

urotoday.com/conference-hig...

Lastly, did you see an RO for possible radiation therapy and if not, why not??

Fish

[StayingOptimistic in reply to NPfisherman]

Thanks for the link. I am seeing a prominent MO at MSK. He asked me to join a clinical trial. It’s randomized to 3 groups( adt, adt plus one drug and adt plus two drugs). I was randomized to the first group only ADT). I am metastatic based on a psma scan but non metastatic according to the old imaging scans, ct, mri and bone scan). I started firmogon 6 months ago, my psa dropped from 1.89 before the start to .05 for the first 4 months and the last 2 months it went up to .07. I asked him may be I should drop out of the trail and add a new drug, he said no, let’s wait and see. So I am nervous. I don’t think the few small psma Mets can be radiated otherwise he would have recommended it

[NPfisherman in reply to StayingOptimistic]

He is not an RO...it is worth seeing an RO just to be sure...my MO told me not to do SBRT to my one met....now, he thinks it was a great idea... he specializes in medicine...your choice of course....

[cujoe in reply to StayingOptimistic]

Please see my short reply to NP below Re: your participation in the clinical trial.

[cujoe in reply to NPfisherman]

I posted the research MD affiliations in the post because I know you go to CC. The two summary tables are good quick references and are alone worth the posting. Hope all is well in the spring garden. Enjoy the week ahead. k9

[NPfisherman in reply to cujoe]

K9 Terror,

Thanks so much for adding that information. Great information, but it let's all of us see how much is here...like a gold mine and more nuggets to follow... The spring garden needs about 1 cubic yard each of garden soil and cow manure... my project for the week....LOL...

Enjoy your week....Happy Easter...

Fish

[NPfisherman in reply to cujoe]

I do LOVE THE CONCLUSION---Options for the treatment of advanced prostate cancer are evolving at an ever-increasing rate. While numerous therapies

have been approved for the castration-resistant and now

castration-sensitive space, more clinical trials are needed to

elucidate the efficacy, necessity and safety of these treatments

for use in earlier disease settings.

Further stratification of patients based on their disease volume

will increasingly change the way we treat advanced prostate

cancer. Ultimately, the goal is to reach a point at which we are

able to completely customize prostate cancer care in a manner

that comprehensively considers patients’ own molecular

phenotype, their disease volume, treatment side-effects and

impact on their overall quality of life.

[cujoe in reply to NPfisherman]

Yes, and we all owe a big debt to CT participants, like Ahk1, who help provide the patient data that will help with that stratification. Sincere thanks to them all. K9

[NPfisherman in reply to cujoe]

Indeed....kudos to Ahk1 for participating in a clinical trial to build knowledge for treating PCa now and for future generations of men... HOORAH !!! as the Marines say...

Fish

[marnieg46]

Thanks for posting this cujoe.

Although I've only skimmed, just reading more closely those parts that I'm more familiar with, I can see it's a great find and I'll definitely spend time trying to make sense of some of the details.

The chart of the various trials on pages 3/4 is very helpful and I'll print them off as a reference when the trial names are mentioned in articles/videos/posts.

I know someone has probably answered this question for me previously or I've read it somewhere...but if so, I've forgotten the answer. What exactly is the criteria used to say someone is remaining hormone sensitive? What is used to determine that one or other of the ADT drugs are no longer working?

[cujoe in reply to marnieg46]

NP can give you a more precise definition than I can, but in general when ADT+ stops being effective. Signs would include rising PSA, increasing/returning bone pain & increasing mets on scans (if metastatic), etc. Non-SOC labs might also be used to determine if the PCa is still responding to ADT+ meds. Current trials (+ many n=1 self-administered trials) are looking at re-sensitizing for specific treatments to extend their effectiveness. All based on K9 imperfect dog-sense

[marnieg46 in reply to cujoe]

It made perfect sense and I now note that as you predict NP would add some more info...Ta

[NPfisherman in reply to marnieg46]

Hi Marnie,

Listen to your K9 amigo... They will not change treatment again usually until nadir ( for Ron --undetectable) plus 2, so around 2 they might add on something else... With his slowly rising PSADT of 6 months, I would not be alarmed... at .2, he could get a PSMA scan to identify any additional mets and maybe consider Lu-177 at that point.... You likely have 1- 2 years on this matter before a decision... apalutamide and darolutamide are more tolerable than Xtandi or Zytiga for f/u post Lu-177. I believe there is a vaccine trial in Oz also for PCa.... another consideration...

Dave

[marnieg46 in reply to NPfisherman]

Thanks Dave for the additional info...Yes K9's answer was very clear and at last appointment a PSMA was mentioned at 0.2 and Lu177. Guess my question was sort of general about how do you 'pinpoint' that a single ADT isn't doing the trick and now I know the answer to that from the Captain and also from 'The Boss' of all things scientific... (apologies to Bruce who by the way is visiting us later this year).

[NPfisherman in reply to marnieg46]

Marnie,

If Ron's PSA continues to rise, then Lupron is no longer "getting it done", but they will likely do nothing until he gets a PSMA scan in a year or so...... I will be writing a post on other options besides SBRT to handle metastases... The treatment regimen is evolving so fast...like the article said, so..... no worries, mate... I'd worry about cardiovascular disease more ...in my opinion...

Dave