An exploratory retrospective multicenter study of prognostic factors in mCRPC patients undergoing enzalutamide treatment: Focus on early PSA decline and kinetics at time of progression

Abstract

Background Recent studies have shown that an early prostate‐specific antigen (PSA) response to androgen receptor‐targeting agents in metastatic castration‐resistant prostate cancer (mCRPC) is associated with a better prognosis. We analyzed the early PSA response to enzalutamide (ENZ) by measuring the PSA doubling time (PSADT) and PSA velocity (PSAV) while monitoring oncologic outcomes and survival in Japanese patients. Methods We analyzed a total of 241 patients with mCRPC who were treated with ENZ. The patients’ median age was 75 ± 7.9 years (range, 53‐93 years). There were 171 (71%) predocetaxel cases, and 70 (29%) post docetaxel cases. PSA‐progression‐free survival (PFS) and overall survival (OS) were assessed according to Prostate Cancer Working Group 2 criteria. This study was approved by the Institutional Review Board of Gunma University Hospital (No. 1595). Results We observed 77 good response (GR; case in which PSA remained low after treatment) cases (31.9%), 125 acquired resistance (AR; decline in PSA after treatment followed by progression) cases (51.9%), and 39 primary resistance (PR; lack of decline in PSA) cases (16.2%). Predocetaxel, PSA‐PFS, and OS were significantly higher compared with post docetaxel (PSA‐PFS: 47.0 vs 13.4 weeks, P < .001; OS: not yet reached vs 80.7 weeks, P < .001). Multivariate analysis of prognostic factors, including PSA response at 4 weeks, was performed using Cox regression analysis. ECOG PS (0 vs 1‐2), hemoglobin (Hb; ≥ 12.2 vs < 12.2 g/dL), time to CRPC ( ≥ 12 vs < 12 m), docetaxel treatment history (no vs yes), and a PSA reduction of 50% at 4 weeks were significant predictors of OS (all, P < .05). In cases of AR (n = 125), multivariate analysis showed that PSA kinetic factors, such as PSADT and PSAV (ng/mL/m), Hb, time to CRPC, PSADT ( ≥ 2 vs < 2 m), and PSAV ( < 20 vs ≥ 20 ng/mL/m), were all predictive of OS following PSA‐progression (P < .05). Conclusions Our study has demonstrated that PSA dynamics after ENZ administration may be a useful prognostic factor for mCRPC patients.

Initial dose reduction of enzalutamide does not decrease the incidence of adverse events in castration-resistant prostate cancer

“…In this study, the multivariate analysis revealed that the time to CRPC within 12 months was the independent predictive factor for poorer PSA-PFS. This finding was consistent with those of previous reports [5,18,19].…”

Reduction of Initial Dose of Enzalutamide does not Decrease the Incidence and Severity of Adverse Events in Castration-Resistant Prostate Cancer

“…In this study, the multivariate analysis revealed that the time to CRPC within 12months was the independent predictive factor for worse PSA PFS, and lower PSA response to enzalutamide treatment was an independent predictive factor for worse OS. These ndings were consistent with those of previous reports (5,16,17), and suggested that enzalutamide might show strong effects if it was administrated at the early phase of CRPC treatment.…”

Prognostic Stratification of Metastatic Prostate Cancer Patients Treated With Abiraterone and Enzalutamide Through an Integrated Analysis of Circulating Free microRNAs and Clinical Parameters

“…Multivariable analysis showed that the plasma level of miR-21 (but not miR-223 or miR-141) was associated with outcome (OS and PFS), independently of other clinical variables. In our evaluation of different clinical parameters usually included in prognostic/predictive models of metastatic prostate cancer (36) time to development of castration resistance and Hb levels were confirmed as independent prognostic factors for OS, findings in line with the results of previous studies of mCRPC patients treated with enzalutamide (37). Interestingly, low Hb levels are also associated with poor survival in several other tumor types (38).…”