Evaluation of Second-Line Treatment for Castration-Resistant Prostate Cancer following the Administration of Upfront Androgen Receptor Signaling Inhibitors

TL;DR

This study found that using androgen receptor signaling inhibitors as second-line treatment for prostate cancer after initial use may be more effective than docetaxel, especially when abiraterone is used first.

Contribution

The study provides new evidence on the effectiveness of treatment sequences for castration-resistant prostate cancer.

Findings

Median progression-free survival was longer with androgen receptor signaling inhibitors than docetaxel in second-line treatment.

Abiraterone as first-line treatment was a prognostic factor for better progression-free survival.

The abiraterone–enzalutamide sequence showed better outcomes than other sequences.

Abstract

This study evaluated the effects of docetaxel and androgen receptor signaling inhibitors as second-line treatments in patients with castration-resistant prostate cancer after androgen receptor signaling inhibitors as first-line treatment. This study retrospectively evaluated the clinical outcomes of second-line treatment with docetaxel or androgen receptor signaling inhibitor in patients with castration-resistant prostate cancer who received first-line treatment with androgen receptor signaling inhibitors. Clinical backgrounds and outcomes were compared between docetaxel and androgen receptor signaling inhibitors as second-line treatment. Of 59 patients, 21 (35.6%) and 38 (64.4%) received docetaxel and androgen receptor signaling inhibitors as second-line treatment after first-line treatment with androgen receptor signaling inhibitors, respectively. In the second-line setting, the median progression-free survival was longer with androgen receptor signaling inhibitor than with docetaxel (17 versus 6 months, P=0.014). In the first-line setting, the median progression-free survival was longer with androgen receptor signaling inhibitors than with docetaxel (32 versus 25 months, P=0.014); however, no significant difference was found in the overall survival. Multivariate analysis revealed that there was no significant association between second-line treatment and survival, and first-line treatment with abiraterone was identified as a prognostic factor for progression-free survival. Subgroup analysis showed that the abiraterone–enzalutamide sequence was more effective than the other three sequences for progression-free survival and overall survival. This study suggests that second-line treatment with an androgen receptor signaling inhibitor for castration-resistant prostate cancer after androgen receptor signaling inhibitors as first-line treatment may be more beneficial, particularly with abiraterone as the upfront treatment.

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