Is There an Optimal Treatment Sequencing Strategy for Metastatic Castration-Resistant Prostate Cancer?

SEOM Clinical Guideline for treatment of muscle-invasive and metastatic urothelial bladder cancer (2016)

“…Somatic mutations of ERCC2, a crucial gene of the nucleotide excision repair pathway, were found in 6–18% of urothelial tumors. These mutations have been associated with response to neoadjuvant cisplatin-based chemotherapy in MIBC patients [7, 11, 53, 54]. …”

Metastatic Castration-Resistant Prostate Cancer: Critical Review of Enzalutamide

“…There are emerging retrospective data on the modest clinical activity observed, as well as on the brief duration of responses with the use of abiraterone after failure of prior docetaxel and enzalutamide therapy 45,46. Given initial approval and widespread use of abiraterone in 2011, and before approval of enzalutamide in 2012, most patients who would have received abiraterone and subsequently switched to enzalutamide may not experience the same benefit as was seen in the AFFIRM trial 41. Further analysis of the AFFIRM trial also shows that in the subgroup analyses, men who had two or more prior chemotherapy treatments did not do as well (with HRs based on the nonstratified proportional hazards model approaching 1), leading perhaps to consideration for earlier hierarchy in the sequencing 47.…”

“…On the other hand, enzalutamide might not be suitable for patients with a history of seizures or who are concurrently receiving medications that lower the seizure threshold-a side effect not seen with abiraterone use. However, there is currently no specific guidelines or biomarkers that would predict the best sequence, 41 timing, and specific population of patients that would benefit from each of those agents. Several groups have advocated for specific guidance on the use of varying approved therapies that look mainly at symptoms, such as the American Urologic Association 42 and the National Cancer Comprehensive Network (NCCN), 43 though with the understanding that given the rapidly evolving changes in the field, tailoring treatment as the therapeutic landscape changes will become appropriate as the literature changes.…”

“…45,46 Given initial approval and widespread use of abiraterone in 2011, and before approval of enzalutamide in 2012, most patients who would have received abiraterone and subsequently switched to enzalutamide may not experience the same benefit as was seen in the AFFIRM trial. 41 Further analysis of the AFFIRM trial also shows that in the subgroup analyses, men who had two or more prior chemotherapy treatments did not do as well (with HRs based on the nonstratified proportional hazards model approaching 1), leading perhaps to consideration for earlier hierarchy in the sequencing. 47 There have been varying hypotheses on the mechanisms of resistance, 48 but cross-resistance conceivably be seen with these agents as well.…”