Switch from prednisone to dexamethasone in metastatic castration-resistant prostate cancer patients progressing on abiraterone plus prednisone / 中华泌尿外科杂志

ABSTRACT

Objective:To evaluate the efficacy and safety of switch from prednisone (AA+ P) to dexamethasone (AA+ D) in metastatic castration-resistant prostate cancer patients (mCRPC) progressing on abiraterone plus prednisone.Methods:Between November 2016 and December 2019, 46 mCRPC patients were switched to AA+ D after progression on AA+ P at Sun Yet-sen University Cancer center. Median age was 72 years(50 to 89 years), with median androgen deprivation therapy (ADT) duration 14.6 months(2.1 to 168.5 months). PSA level at the time of diagnosis, the initiation of AA+ P treatment, the time of switch were 258.9 ng/ml, 56.6 ng/ml, 25.1 ng/ml, respectively. 42 (91.3%), 12(26.1%), 7(15.2%) patients had bone metastasis, lymph node metastasis, visceral metastasis, respectively. 28 patients had Gleason score ≥8, and 11 patients had Gleason score<8. The primary endpoint was progression free-survival (PFS). Secondary endpoints included PSA response rate of PSA decline ≥50% and ≥30% and safety. Patients were divided into different risk level groups according to PSA level at the time of switch and PFS on AA+ P.Results:The median follow-up of 46 patients was 4.9 months, 40 patients progressed at the last follow-up, the treatment was terminated in 1 patient because of cerebral infarction, 5 patients were still on the treatment of AA+ D. Median PFS on AA+ D of 46 patients was 3.7 (1.6-24.1) months. A total of 12 (26.1%) patients showed a PSA decline≥50% after treatment with AA+ D, and 21 (45.7%) patients showed a PSA decline ≥30%. The median PFS was 8.5 (2.7-24.1) and 3.0 (1.6-17.8) months for patients with PSA decline≥50% and PSA didn’t decline ≥50%, respectively. Four factors below were significantly associated with a longer PFS on AA+ D after steroid switch in univariate analysis: lower PSA level at the time of switch (<30 ng/ml, HR=0.30, 95% CI 0.14-0.64, P=0.002), longer ADT sensitivity duration (≥18 months, HR=0.55, 95% CI 0.28-1.06, P=0.045), longer AA+ P treatment PFS (≥8 months, HR=0.36, 95% CI 0.18-0.72, P=0.004), and greater PSA decline on AA+ D (≥50%, HR=0.30, 95% CI 0.17-0.75, P=0.007). The above mentioned factors were also independent prognostic factors associated with better PFS on AA+ D after steroid switch in multivariate analysis. Treatment with AA+ D was well tolerated in all patients, with no grade 3/4 toxicity reported. Conclusions:Switching from prednisone to dexamethasone is effective and safe in mCRPC patients progressing on abiraterone plus prednisone. Patients with lower PSA level at the time of switch, longer ADT sensitivity duration, longer AA+ P treatment PFS and greater PSA decline on AA+ D might gain better efficacy.