Table A1.

Indications and Regulatory Labels for the Currently Approved Drugs for CRPC, Aligned With the PCWG3 Manifestation-Specific Outcome Framework

Early manifestations (response): control, relieve, or eliminate

Approved to control pain or indicated for patients with symptoms

Mitoxantrone plus prednisone for the treatment of patients with pain related to advanced hormone-refractory prostate cancer

89Sr for the relief of bone pain in patients with painful skeletal metastases

153Sm for relief of pain in patients with osteoblastic metastatic bone lesions that enhance on radionuclide bone scan

Radium-223* (symptoms from bone metastases with no involvement of other organs)

No FDA drug approvals on the basis of:

PSA declines

Tumor shrinkage

Bone scan improvement

Changes in circulating tumor cell number

Later manifestations (progression): delay or prevent

Approved or shown to delay SREs or SSEs

Zoledronic acid (SRE)

Denosumab (SRE)

Abiraterone acetate (SRE)*,†

Enzalutamide (SRE)*,†

Radium-223 (SSE)*,‡

Approved for delay of death (survival)

Docetaxel

Sipuleucel-T

Cabazitaxel

Abiraterone acetate plus prednisone

Enzalutamide

Radium-223

Delay of radiographic progression using PCWG2-based criteria, coprimary with survival

Abiraterone acetate plus prednisone

Enzalutamide

Abbreviations: CRPC, castration-resistant prostate cancer; FDA, United States Food & Drug Administration; PCWG2, Prostate Cancer Clinical Trials Working Group 2; PCWG3, Prostate Cancer Clinical Trials Working Group 3; PSA, prostate-specific antigen; SREs, skeletal-related events; SSEs, symptomatic skeletal events.

^*Indicated for patients with symptoms.

^†Shown to delay SREs.

^‡Shown to delay SSEs.