Taxanes Versus Androgen Receptor Therapy as Second-Line Treatment for Castrate-Resistant Metastatic Prostate Cancer After First-Line Androgen Receptor Therapy

• Published in: Clinical genitourinary cancer 2023-06, Vol.21 (3), p.349-356.e2
• Main Authors: Broyelle, Antonin, Delanoy, Nicolas, Bimbai, André-Michel, Le Deley, Marie-Cécile, Penel, Nicolas, Villers, Arnauld, Lebellec, Loïc, Oudard, Stéphane
• Format: Article
• Language: English
• Subjects: Abiraterone; Enzalutamide; Humans; Life Sciences; Male; Nitriles; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant - pathology; Receptors, Androgen; Retrospective Studies; Sequence; Taxane; Taxoids; Treatment Outcome
• ISSN: 1558-7673; 1938-0682
• DOI: 10.1016/j.clgc.2023.02.006

•The optimal therapeutic sequence for mCRPC is unclear.•There is no difference in OS/PFS between first-line abiraterone and enzalutamide.•In second line, docetaxel is better than androgen-receptor therapy.•Efforts must be made to better select the optimal first- and second-line treatments. The optimal therapeutic sequence for metastatic castrate-resistance prostate cancer (mCRPC) is still debated. This study aimed to compare activity of taxanes (TAX) versus that of androgen-receptor therapy (ART) in men with mCRPC treated with first-line ART. This retrospective study included all consecutive chemo-naive mCRPC patients who have received first-line ART treatment. Progression-free survival (PFS) and overall survival (OS) were compared between patients treated with second-line ART or TAX. Overall, 175 patients treated with first-line enzalutamide (ENZA, n = 75) or abiraterone (ABI, n = 100) were evaluated. Among them, 69 (39%) and 30 (17%) patients received second-line TAX and ART, respectively, while 76 (43%) patients did not receive further treatment. From the start of first-line therapy, the median PFS and OS were 13 months (95% CI: 11-15) and 34 months (95% CI: 29-39), respectively, without any significant difference between ENZA and ABI. From the start of second-line therapy, the median PFS and OS were 6 months (95% CI: 5-7) and 18 months (95% CI: 14-21), respectively. Compared with ART, docetaxel was associated with significantly higher prostate-specific antigen (PSA, ≥ 50%) (29% vs. 0%, P < .001) and radiological responses (21% vs. 0%, P < .001). PFS was longer in TAX than in ART (6.7 months vs. 4 months, HR: 0.63, 95% CI: 0.41-0.96, P = .034), but there was no significant difference in OS (19 months vs. 12 months, P = .1). After propensity score adjustment, PFS (P = .2) and OS (P = .1) were similar between second-line TAX and ART. In the second-line setting, TAX provides higher PSA and radiological responses than does ART for mCRPC patients who received first-line ART, but the PFS and OS are similar. This study provides new elements to help deciding the best treatment sequence. The optimal therapeutic sequence for metastatic castrate-resistance prostate cancer is still debated. We included all consecutive chemo-naive mCRPC patients who have received first-line ART in two hospitals in France. In the first-line setting, there was no significant difference between abiraterone and enzalutamide. In the second-line setting, taxanes was superior to androgen-r