SIU 2017: Non-Androgen-Receptor-Targeted Options for mCRPC

Lisbon, Portugal (UroToday.com) The CHAARTED and STAMPEDE studies demonstrated that administration of Docetaxel in metastatic hormone sensitive prostate cancer (mHSPC) reduced the risk of death by 39%, creating a trend of giving these advanced lines of treatment earlier than in the past. Dr. Saad therefore asks the following question: Since androgen deprivation therapy (ADT) is the standard first line treatment of metastatic castrate resistant prostate cancer (mCRPC), is chemotherapy effective after hormonal therapy? The COU-AA-302 study examined this question by administration of docetaxel post abiraterone, and demonstrating a PSA fall by 50% in almost 50% of the patients. Another study – TROPIC, analyzed administration of Cabazitaxel after docetaxel and compared it to mitoxantrone. This study also had positive results with increase of overall survival by a median of 2.4 months.

Chemotherapy should be given upfront in mCRPC in patients with high burden of disease with low PSA, high burden visceral metastases, moderate-severe symptoms, minimal response to primary ADT, and perhaps to known AR-V7 splice variants. All these represent approximately 10-20% of patients.

Dr. Saad later discussed the problems associated with bone metastases, which are the cause of most of the morbidity and increased mortality. These problems include pathologic fractures, spinal cord compression, which lead to palliative radiotherapy and surgery to the bone. It is important to remember that Zoledronic acid and Denosumab significantly delay and reduce the risk posed by bone metastases. Dr. Saad also mentions the Radium-223 alpha emitter therapy, which has been shown in the ALSYMPCA trial to improve overall survival, and reduce time to first symptomatic skeletal event after 5-6 injections, when compared to placebo. Lastly, it is important to mention that benefit has also been shown when bone targeted therapy is combined with abiraterone in chemo-naïve mCRPC patients, in the COU-AA 302 trial. In a similar fashion, the TRAPEZE trial demonstrated that in mCRPC patients the combination of docetaxel and zolderonic acid improve skeletal related event free survival. Lastly, combining bone targeted therapies with Radium-223 has also been shown to be beneficial. These drug combinations are the future of trials in this realm of prostate cancer (PC), according to Dr. Saad. 

Dr. Saad concluded his presentation by stating that thus far, immunotherapy, including CTLA-4 inhibition, PD-1 blockade, and vaccines have been disappointing in PC. Lastly, Dr. Saad also mentioned the trial he is conducting to assess the effect of physical exercise on the survival of mCRPC patients. The future of mHSPC and mCRPC should encompass trials assessing novel, targeted and multimodal therapies.

Presented by: Fred Saad

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre.Twitter: @GoldbergHanan at the 37th Congress of Société Internationale d’Urologie - October 19-22, 2017- Lisbon, Portugal
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