Abstract
Background: There is emerging evidence that radiographic progression-free survival (rPFS) is highly correlated with overall survival (OS), potentially serving as an indicator of treatment outcome for castration-resistant prostate cancer (CRPC). The objective of this study is to assess rPFS and prostate specific antigen (PSA) response in sequential treatment using androgen signaling inhibitors (ASIs) including abiraterone and enzalutamide in newly diagnosed CRPC. Methods: Propensity score matching was performed to reduce bias by confounding factors between first-line ASIs. The primary endpoints of the study included rPFS, time to PSA progression (TTPP), and PSA response. Results: A paired-matched group of 184 patients were identified. From the initiation of first-line ASIs, there was no significant difference in rPFS, TTPP, and PSA response between treatment arms. From the initiation of second-line ASIs, enzalutamide following abiraterone consistently exhibited longer rPFS (median: 7 and 15 months, p = 0.04), TTPP, and better PSA response compared to the reverse, whereas OS did not reach significance (median: 14 and 23 months, p = 0.35). Conclusion: Although the effect of ASIs as the first line was similar, the extent of cross-resistance might differ towards less resistance in enzalutamide following abiraterone than the reverse.
Highlights
Prostate cancer is one of the most common malignancies in men [1]
NCT02125357) using these androgen signaling inhibitors (ASIs) [28] exhibited that prostate specific antigen (PSA) response and time to PSA progression (TTPP) on second-line ASIs were significantly associated with favorable outcomes in patients treated with enzalutamide following abiraterone
Of all 357 castration-resistant prostate cancer (CRPC) patients in the cohort, 242 patients were treated with either abiraterone (113 patients) or enzalutamide (129 patients) as the first-line treatment
Summary
Prostate cancer is one of the most common malignancies in men [1]. androgen deprivation therapy (ADT) offers certain remissions lasting 1 to 2 years in most patients, cancer cells eventually develop castration-resistant prostate cancer (CRPC) through multiple mechanisms [2,3,4,5]. There have been a myriad of retrospective studies reporting the sequential use of ASIs for the treatment of CRPC—namely ‘abiraterone following enzalutamide’ and ‘enzalutamide following abiraterone’ [14,15,16,17,18,19,20,21,22,23,24,25,26] The data from these results seems to indicate cross-resistance between these ASIs. In particular, a modest response of abiraterone after progression on docetaxel and enzalutamide was observed in patients after discontinuation from the AFFIRM trial [7], in which less than 10% of patients achieved a ≥50% decline of prostate specific antigen (PSA) with subsequent abiraterone [18,21]. Conclusion: the effect of ASIs as the first line was similar, the extent of cross-resistance might differ towards less resistance in enzalutamide following abiraterone than the reverse
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