The clinical benefit of sequential therapy with androgen receptor axis‐targeted agents alone in patients with castration‐resistant prostate cancer: A propensity score‐matched comparison study

Abstract

Background: The optimal sequential therapy for castration-resistant prostate cancer (CRPC) remains unknown. In recent years, some doubts have emerged regarding the clinical benefit of sequential therapy with androgen receptor axistargeted agents (ART) such as abiraterone (ABI) or enzalutamide (ENZ) for patients with CRPC. We compared the effect of ART-to-ART (AA) sequential therapy after castration resistance with that of docetaxel (DTX)-combined sequential therapy (ART to DTX or DTX to ART) in patients with CRPC. Methods: We retrospectively identified and analyzed the data of 315 patients with CRPC treated in our seven affiliated institutions between 2009 and 2019. All patients received either DTX or ART (ABI or ENZ) as the first-or second-line therapy after castration resistance. We compared the overall survival (OS) and the second progression-free survival (PFS2), calculated from the initiation of first-line therapy after castration resistance, between the AA sequence group and the DTX-combined sequence group. PFS2 was defined as the period from the start of first-line treatment after castration resistance to progression on second-line treatment. To minimize selection bias from possible confounders, we performed propensity score matching using one-to-one nearest neighbor matching without replacement. Results: Overall, 106 and 209 patients were administered the AA sequential therapy and DTX-combined sequential therapy, respectively. The clinicopathological variables of patients were well balanced after propensity score matching, and there were no significant differences between the two groups. In the propensity scorematched cohort, OS was not significantly different between the two groups (median, 37.9 vs. 45.4 months; hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.68-1.79; p = .701), while PFS2 was significantly shorter in the AA group than in

Treatment Sequences of Androgen Receptor–Targeted Agents for Prostate Cancer

“…The primary outcome in the retrospective medical record review study 9 was OS, which was defined as the period from the start of first-line treatment after resistance to castration to death of any cause. The secondary outcome was PFS, which was defined as the period from the start of first-line treatment after resistance to castration to progression on second-line treatment.…”

“…Both of the included primary studies 9,10 were retrospective in design: 1 was a medical record review 9 and the other was a registry review. 10 One study 9 used propensity score matching to minimize selection bias from potential confounders.…”

“…The retrospective medical record review study 9 included 315 DTX/ARTA-naïve CRPC patients who were treated with first-line ARTA (i.e., AA or ENZ) or DTX followed by second-line DTX or ARTA. Patients' ages ranged from 67 years to 82 years, and approximately half of the patients had a Gleason score of 9 or greater.…”

“…The retrospective medical record review study 9 compared the effect of ARTA (AA or ENZ) sequential therapy with DTX-containing sequential therapy. There were 2 main groups of patients: those treated with ARTA followed by ARTA (ARTA-to-ARTA), and those treated with ARTA followed by DTX (ARTA-to-DTX) or DTX followed by ARTA (DTX-to-ARTA).…”

“…The retrospective medical record review study 9 found that sequential treatment of ARTAto-ARTA was associated with significantly shorter PSA-PFS compared with DTX-containing sequential therapy (i.e., DTX-to-ARTA or ARTA-to-DTX). Median PFS values were 13.7 and 18.9 months, respectively (HR = 1.65; 95% CI, 1.23 to 2.17; P < 0.001).…”