Metastatic Castration-resistant Prostate Cancer
In the near future, it will be crucial to test the concomitant administration of enzalutamide and abiraterone more than the definition of the best sequence, especially in early disease stages, in which there is a higher chance of cure. In an ongoing feasibility Phase II study (NCT01650194), abiraterone and enzalutamide are being administered simultaneously to CRPC bone metastatic patients: in 41 patients, it was observed that the combination has a favorable safety profile and the PSA response is promising (48% of patients experienced PSA declines ≥90% and 72% of patients experienced PSA declines ≥50%).
Another relevant challenge is determining how to improve the efficacy of first-line docetaxel treatment: several drugs tested in combination with docetaxel showed promising activity in Phase II trials, but these results were not confirmed in Phase III trials. Many study drugs failed to improve OS when associated with docetaxel: atrasentan and zibotentan (endothelin A receptor antagonists), bevacizumab (a monoclonal antibody inhibiting VEGF), lenalinomide (an angiogenesis inhibitor), aflibercept (a fusion protein of IgG1 and VEGFR1) and DN101 (a highly active form of vitamin D) all failed to show improvements in OS. Moreover a study comparing cabazitaxel 25 mg/m versus cabazitaxel 20 mg/m versus standard first-line docetaxel chemotherapy is underway (FIRSTANA; NCT01308567).
All of the aforementioned new therapeutic strategies have to be tailored to the patient's cancer biology in order to personalize treatment. Notably, a significant portion of mCRPC patients did not respond to new androgen-targeting and chemotherapeutic agents. A better understanding of new drug resistance mechanisms and prostate cancer molecular subtypes based on genomic and proteomic analysis, as well as prognostic and predictive biomarkers, may further improve mCRPC treatment. To date, these studies are in the early phases and all recent drug approvals for CRPC lack predictive biomarkers that can help with selecting patient subgroups. Future efforts have to be made in order to tie prostate cancer biology to therapy so as to maximize benefit and minimize toxicity and costs.
Conclusion & Future Perspective
In the near future, it will be crucial to test the concomitant administration of enzalutamide and abiraterone more than the definition of the best sequence, especially in early disease stages, in which there is a higher chance of cure. In an ongoing feasibility Phase II study (NCT01650194), abiraterone and enzalutamide are being administered simultaneously to CRPC bone metastatic patients: in 41 patients, it was observed that the combination has a favorable safety profile and the PSA response is promising (48% of patients experienced PSA declines ≥90% and 72% of patients experienced PSA declines ≥50%).
Another relevant challenge is determining how to improve the efficacy of first-line docetaxel treatment: several drugs tested in combination with docetaxel showed promising activity in Phase II trials, but these results were not confirmed in Phase III trials. Many study drugs failed to improve OS when associated with docetaxel: atrasentan and zibotentan (endothelin A receptor antagonists), bevacizumab (a monoclonal antibody inhibiting VEGF), lenalinomide (an angiogenesis inhibitor), aflibercept (a fusion protein of IgG1 and VEGFR1) and DN101 (a highly active form of vitamin D) all failed to show improvements in OS. Moreover a study comparing cabazitaxel 25 mg/m versus cabazitaxel 20 mg/m versus standard first-line docetaxel chemotherapy is underway (FIRSTANA; NCT01308567).
All of the aforementioned new therapeutic strategies have to be tailored to the patient's cancer biology in order to personalize treatment. Notably, a significant portion of mCRPC patients did not respond to new androgen-targeting and chemotherapeutic agents. A better understanding of new drug resistance mechanisms and prostate cancer molecular subtypes based on genomic and proteomic analysis, as well as prognostic and predictive biomarkers, may further improve mCRPC treatment. To date, these studies are in the early phases and all recent drug approvals for CRPC lack predictive biomarkers that can help with selecting patient subgroups. Future efforts have to be made in order to tie prostate cancer biology to therapy so as to maximize benefit and minimize toxicity and costs.
SHARE
![Pediatric Supportive Care (PDQ®): Supportive care - Patient Information [NCI]-Overview](https://cdnus.oss-us-west-1.aliyuncs.com/libs/images/NewsJpg/cate_6/072_215x160.jpg)
