The study showed that nearly two-thirds of the patients in the study had aberrations in the AR and 14% of patients in the study had a mutation in the BRCA1 or BRCA2 gene. Mutations in these two BRCA genes are already known to increase breast and ovarian cancer risk. PARP inhibitors have already been approved in BRCA-positive ovarian cancer and these new findings suggest PARP inhibitors could be effective in some prostate cancers.

“We found that over 20% of patients with mCRPC had mutations in DNA repair pathway genes such as BRCA2 and BRCA1. This would suggest that this subset of patients may benefit from PARP inhibitors or platinum-based therapies,” Dr. Chinnaiyan told Cancer Therapy Advisor.


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The study showed that 8% of patients had an inherited genetic alteration, suggesting genetic counseling may be appropriate for patients with metastatic prostate cancer. A unique feature of this study is that it used fresh biopsy samples from living patients with mCRPC.

Typically, it has been difficult to obtain a large enough quantity of quality tumor tissue, especially from bone biopsies, to make sequencing possible.

Mark Garzotto, MD, who is an associate professor of urology and radiation medicine at Oregon Health & Science University Knight Cancer Institute in Portland, OR, said the findings are significant and could help usher in a new era in the treatment of metastatic disease.

“However to advance the science further we must look beyond just the AR towards other mechanisms of cancer progression. This will require developing effective combinations such as anti-AR therapy with chemotherapy and radiation,” Dr. Garzotto told Cancer Therapy Advisor.

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“Two such studies being carried out by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group aim to combine enzalutamide with radiation for localized cancer and with standard hormone therapy for metastatic cancer. Another combination that looks promising is anti-AR therapy with docetaxel chemotherapy,” said Dr. Garzotto.

He said “the Holy Grail” in treating cancer is long-term disease control. That has been elusive. However, Dr. Garzotto said the trial data on the use of immunomodulators for cancer have shown that some of the most lethal cancers may be well-controlled and in some cases result in long-term survival.

Reference

  1. Robinson D, van Allen EM, Wu Y-M, et al. Integrative clinical genomics of advanced prostate cancer. Cell. 2015;161(5):1215-1218.