I'm travelling and using an unfamiliar tablet, so no cut and paste from these linked articles. Note the access to a PDF of the full Grand Rounds paper in the second linked article. It has a useful table and simplified treatment algorithm for those mCRPCa with actionable genetic mutations.
A Roadmap for Clinicians on How to Navigate Prostate Cancers With Actionable Mutations – Oncology Grand Rounds paper eloquently tackles the issues, by Nataliya Mar, MD, September 26, 2023.
The armamentarium of prostate cancer therapies expanded in 2020 to include the first genomically targeted agents. Men with both somatic and germline alterations in the DNA damage repair (DDR) pathway, most commonly BRCA2, are now candidates for pathway with poly-ADP ribose polymerase (PARP) inhibitors.
These drugs are used as either single agents or in combination with novel hormonal therapies (NHTs) in the metastatic castrate-resistant setting. However, multiple agents have been approved, with varying prior therapy requirements and different companion drugs when used in combination.
Although having options is good, this creates at least some ambiguity for clinicians. Another question to consider is whether all DDR pathway alterations are created equal and whether there should be the same enthusiasm to use PARP inhibitors for non-BRCA alterations.
This Oncology Grand Rounds paper eloquently tackles these issues and lays out a roadmap for clinicians on how to navigate prostate cancers with actionable mutations. It also dissects the recently published MAGNITUDE and PROPEL trials that combined PARP inhibitors with NHTs in the first-line metastatic castrate-resistant setting.
Despite this rapidly evolving data, one decision remains clear and simple for clinicians: the choice to order both somatic and germline genomic testing for men with advanced prostate cancer to identify possible DDR pathway alterations and give their patients an extra treatment option.
Nataliya Mar, MD, is associate clinical professor in the Division of Hematology/Oncology at the Chao Family Comprehensive Cancer Center, UCI Health, in Orange, California.
MedPage Today, ASCO > Prostate Cancer, ASCO > Prostate Cancer, A Roadmap for Clinicians on How to Navigate Prostate Cancers With Actionable Mutations – Oncology Grand Rounds paper eloquently tackles the issues, by Nataliya Mar, MD September 26, 2023
The full PDF download of the Grand Rounds paper and interview about it are here.
MedPage Today, ASCO > Prostate Cancer, Acting on Actionable Mutations in Metastatic Prostate Cancer – An ASCO Reading Room selection, September 21, 2023, by Catherine H. Marshall, MD, MPH, Journal of Clinical Oncology
I am a poster child for this very thing... Due to family history, I requested my RP tissue be tested for genomics thinking about simply having extra possible avenues of attack should they be needed. I did this early in my journey. Interestingly, I learned that the tissue present in the gland, isn't necessarily the same cell type or tissue that becomes agreesive and spreads, if it does later. Case in point was my Prostate tissue had 'zero' genomic markers present.
Fast forward to the inadvertent discovery of metastasis during an attempted appendectomy a few years later while PSA had returned and was climbing rapidly, and subsequent surgery to remove lesions which were found in my peritoneal. This tissue I request also be tested and compared to the original. Well, the metastatic tissue had 11 genomic markers present, compared to zero before. Yes, a shocker! And 3 possibly actionable, with one being the BRCA Gene (deletion).
Chemo followed the metastasis with ADT then for life. After a brief run with Orgovyx afterwards that failed, and identifying possible recurrent metastatic tissue once again, we switched to Degarelix, added an second generation inhibitor Darolutamide, then radiated any suspect mets found (whack-a-mole), afterwards putting the icing on the cake with Lynparza for the BRCA gene.
So far... So good! And as a result of my personal experience, I believe this testing should be made standard for any metastatic tissue found on a patient. Biggest issue we have is our individual disease being treated for what it is, rather than being placed into a group and a risk assessment being made by the group performance and history rather than what our personal diagnosis is telling us.
Otherwise, it is important to remember that there are what, over 500 markers associated with PCa. But only a handful of drugs available, and fewer approved based upon the markers alone. So genomics isn't the end-all answer, but as noted above, is certainly welcomed to add for, and allow, another avenue or to travel on this journey or another tool we can use in the fight!
I also had genetic testing done on tissue from my final biopsy with zero mutations noted. (And coming from a family with LOTS of multi-generational cancer, I was more than surprised of that result)
This post from a year back is the one that helped me understand the wide-ranging heterogeneity of PCa and the challenge that presents for treatment:
Spatially resolved clonal copy number alterations in benign & malignant tissue (i.e., prostate tissue)- Nature, Published online 2022 Aug 10
It is more than clear that the more we know about the genetic characteristics (and hormone drivers), the better judgements we can make about current/future treatment options.
Thanks for sharing your experience and gained insights. Stay S&W,
Our thoughts are the same on the genetic testing and so few drugs... I believe this will improve as we find more "crossover" types of drugs in other cancer types being able to impact targets in PCa, much like PARPS...
What we need are more of those types of drugs, as well as non-AR types of drugs that target other areas of prostate cancer....Why hasn't a number of promising drugs failed to move on to Phase III from a successful Phase II???
Small biotechs need more options in getting their candidates into/past Phase III...
There are many great MO (including dr Kwon, I love him because he is a fellow guitarist!) who recommend periodical genetic panel because cancer evolves and can get flawed! So it becomes extremely important to have it watched closely throughout the journey.
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