Genomic Analysis of Three Metastatic Prostate Cancer Patients with Exceptional Responses to Carboplatin

[Balsam01]

sciencedirect.com/science/a...

this very dense article contains anecdotal hope for BRCA2 deficiencies. Here is the discussion:

2. Discussion

Platinum-based chemotherapy has demonstrated impressive anti-tumour activity in some mCRPC patients; however, little published data are available on the different tumour DNA repair defects associated with platinum sensitivity. These three patients shared some atypical clinical features: a strong family history for cancer, presentation with metastatic disease, young age at diagnosis, and low PSA levels relatively to the extent of their metastatic disease. Interestingly, the first two patients were given carboplatin based solely on these clinical characteristics. The availability of NGS subsequently allowed us to elucidate the underlying genomic characteristics of these tumours.

The first patient had exhausted all of the standard treatment options and had rapidly progressive symptomatic disease before initiation of carboplatin which has given him further more than 3 yr of disease control and excellent quality of life. We were unable to identify a specific genetic defect responsible for his remarkable platinum sensitivity although WES demonstrated a mutational signature of HRD. The second patient has a germline BRCA2 mutation previously reported to confer a poorer prognosis [8]; however, impressively, he is still alive 15 yr later which compares favourably to the median survival of 6 yr on the CHAARTED trial [9] and 6.4 yr on the STAMPEDE trial [10]. These data suggest that as with ovarian cancer, platinum treatment may convert this aggressive disease subtype into a better prognosis disease. Our third patient presented with a deleterious germline ATM mutation, and his response to carboplatin arguably supports the functional impact of this genomic aberration.

In conclusion, these case series suggest the efficacy of carboplatin in metastatic prostate cancer with DNA repair defects. Further clinical trials are warranted to support its use in this subset of patients. Our report indicates that treatment selection can be facilitated by family history records as well as NGS of germline and somatic cancer DNA.

[ronnie1943]

Hi,...my husband is on carboplatin chemo. He is getting it every three weeks until it quits working for him. He has had Seven treatments so far. PSA had risen to close to 700 before going on this chemo. This past PSA was 22. Due for a cat scan in two weeks, hoping for some good news... He is a ten year survivor,His cancer is now in his lymph nodes, liver and has from the beginning been in gone bone. Any thoughts of this chemo helping getting rid of tumors in liver.?? On pins and needles waiting for the cat scan results.

Take care, good luck and good health.

Lynn/caregiver Pa.