Info about parp inhibitors for BrCa2 positive

My husband, aka JohnKeats, passed away in April from metastatic prostate cancer. He was only 52. He survived 6 years beyond a stage 4 diagnosis, when he was given only 18 months. This was due in large part to an experimental parp inhibitor which worked to correct the BrCa gene mutation. He lead a relatively normal live, as normal as can be while lupron for 6 years.

In December he started feeling ill with flu like symptoms. We learned then that his cancer developed into such an aggressive form that it did not respond to any treatment and quickly spread to his bone marrow, which ended his life very quickly. His oncologist admitted that long term patients on parp inhibitors are sometimes having the result of experiencing a "super" cancer that no longer responds to treatment.

We traveled to England in October, and he was feeling great, so this came on very quickly, and he was gone six months later. As his wife and life partner, I don't think we would have done anything differently, the parp inhibitor (though clinical trial) gave him six years that he would not have otherwise had, and being a pill form he had little side effects. However it would have been helpful to know that this super cancer was being observed in others taking the drug, so we could have been more vigilant. Perhaps it would have bought him more time, perhaps not.

Just wanted to share this information for those in the same situation. I also wanted to post about his passing. Blessings to you all,

Mrs. JohnKeats

I am saddened to hear this. I followed his posts with great interest, and I think he helped many people. Your comments about PARP inhibitors are especially interesting. It is really the only class of medicines we have against DNA repair defects. You raise some interesting questions in my mind:

While they slow progression in the short run, is there a benefit in terms of overall survival and quality of life? Only the clinical trial that he courageously volunteered for can answer that. In his case, 6 years of survival was certainly more than one would reasonably expect, and I hope it improved his quality of life too, during that time.

Does it select for more virulent cancer variants? Our current understanding is that cancer is a tissue-based disease. Various types of cells interact and encourage nearby cells to be more like them. Eliminating one specific cell type may allow another to take over. This is a fear for ADT- does it eliminate the hormone-sensitive cells and allow the castrate-sensitive ones to take over? The evidence so far has been that there is a net benefit. But when we deal with these rare cell types, that may or may not be true.

The other open question is about the relative effectiveness for germline or somatic genotype. Your husband had the rare BRCA2 germline mutation, as I recall, meaning it affected all his cells since birth. Somatic mutations - cancer cells that acquire DNA-repair defects - seem to occur over time in prostate cancer metastases and are less rare, affecting about 5% of men with mCRPC. The question is - is there any survival benefit in using PARP inhibitors to decrease the population of those mutated cells?

Thank you so much for posting. This will be important to many men that follow your husband.

Mrs. JohnKeats,

So sorry for your loss. Thank you for your post.

I, too, followed your husband's posts. Unknowingly, he had helped many guys with PC and the unique thing about this site is that he will help guys for years to come.

Thanks again,
Jerry