Prostate cancer expert Dr Smith elaborates on treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed on systemic therapy.
Matthew R. Smith, MD, PhD: For most patients in our practice, the second drug after androgen deprivation therapy is an androgen receptor pathway inhibitor, and that would be true in either metastatic castration-sensitive prostate cancer, non-metastatic CRPC, or in mCRPC. With progression on an androgen receptor pathway inhibitor, we have choices. The disease state we're now talking about would be patients with mCRPC and disease progression despite prior androgen receptor pathway inhibitors. Among available approved options, our standard approach would be to use docetaxel. That's not a decision we would take lightly. An important point to make here is that we wouldn't switch systemic treatments in this setting based on PSA progression alone. We would continue the androgen receptor pathway inhibitor until radiographic and/or clinical progression.
There are now newer options for at least molecular subsets of patients in this disease state, including olaparib, based on the results of the pivotal PROfound (NCT02987543) study. The study included patients with mCRPC and disease progression on an androgen receptor pathway inhibitor and patients could also have received prior docetaxel, and about half of the patients did receive that. PROfound also included patients with a germline or somatic mutation in a DNA repair gene, and it showed an improvement in progression-free and overall survival in favor of olaparib, at least in the BRCA1 and BRCA2 primary cohorts. This is important information and a strong rationale to do tumor genetic testing and germline genetic testing in patients. We typically offer germline genetic testing for all of our patients at diagnosis with metastatic prostate cancer and then do tumor genetic testing typically after they develop mCRPC and progression after first-line treatment.
Transcript edited for clarity.
Case: A 82-Year-Old Man with Metastatic Castration-Resistant Prostate Cancer
Sept. 2016
Initial presentation
Clinical workup
Treatment
April 2018
The RAPSON trial found that receiving radium-223 prior to docetaxel in patients with metastatic castration-resistant prostate cancer improved quality of life and tolerability compared to the reverse sequence, without affecting progression-free survival or overall survival.
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