Genetic mutations: New therapeutic avenues in metastatic prostate cancer

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Published: 9 Feb 2018
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Dr Joaquin Mateo - Vall d'Hebron Institute of Oncology, Barcelona, Spain

Dr Mateo speaks with ecancer at the 2018 ASCO Genitourinary Cancers Symposium about findings from a retrospective and international study showing for the first time that patients with inherited DNA repair mutations benefit from standard therapies in a similar way to other metastatic prostate cancer patients.

He states that results were analysed for a total of 390 metastatic prostate cancer patients with DNA-repair gene mutations to assess response to standard treatments.

He goes on to highlight that findings indicate that patients with BRCA mutations respond to these therapies in a similar way to other patients with metastatic prostate cancer patients without these mutations. Overall survival and disease-free progression were therefore comparable and no significant differences in response rate to first-line treatment were observed. 

In the last few years there has been a huge effort by the academic community to discern the genomic landscape of lethal prostate cancer. Since a couple of years ago we have come with a good classification of the different subtypes of prostate cancer that we have. So now what we are doing is we are trying to look at whether these different genomic subtypes of prostate cancer respond differently to treatments. What we presented here at GU ASCO was an international study with our collaborators in New York, Seattle and Melbourne where we looked at whether the fact of having a particular mutation that infers genetic predisposition to have prostate cancer would affect the way that these patients respond to different treatments. What we saw is that actually even if you have this mutation that has been previously described to increase the risk also of breast and ovarian cancer and determine how these patients respond to different therapies, in prostate cancer these patients seem to still benefit from the standard of care therapies. But also we analysed how they respond specifically to new drugs that are now in development that are the same that are being used for breast and ovarian cancer and we got our first set of data supporting that these patients benefit particularly from these therapies.

So we looked at whether patients having or not having these inherited mutations that occur in about one in ten patients with advanced prostate cancer respond the same as the rest of the population to standard of care drugs like abiraterone, enzalutamide and taxanes. What we observed is that actually they do quite well on chemotherapy with taxanes and this corroborates what has been seen in several studies published in the last year. What was interesting was that we saw similar benefit derived from standard of care abiraterone and enzalutamide. This is a bit different to what has been shown in other studies, particularly in a cohort of patients from Canada, and probably reflects that we still don't understand fully the complexity of these different genomic backgrounds and how they determine the response to therapy.

What are the potential implications of this?

The implications are double. First of all we think that patients that have these inherited mutations may actually benefit from specific tailored treatments for them and we are running now phase II and phase III trials to validate this data. But, secondly, we are reassured that these patients still respond to the standard of care therapies so having found this mutation should not discourage physicians to offer these patients hormonal treatments.