Randomized phase II multicenter trial of abiraterone acetate with or without cabazitaxel in the treatment of metastatic castration-resistant prostate cancer Journal Article

  

Authors:	Slovin, S. F.; Knudsen, K.; Halabi, S.; de Leeuw, R.; Shafi, A.; Kang, P.; Wolf, S.; Luo, B.; Gopalan, A.; Curley, T.; Fleming, M.; Molina, A.; Fernandez, C.
Article Title:	Randomized phase II multicenter trial of abiraterone acetate with or without cabazitaxel in the treatment of metastatic castration-resistant prostate cancer
Abstract:	PURPOSE: Improving clinical outcomes with novel drug combinations to treat metastatic castration-resistant prostate cancer (mCRPC) is challenging. Preclinical studies showed cabazitaxel had superior antitumor efficacy compared with docetaxel. Gene expression profiling revealed divergent effects of these taxanes in cycling cells. mCRPC are RB deficient rendering them hypersensitive to taxanes. These data suggested that upfront treatment with cabazitaxel with abiraterone may affect therapeutic response. We designed a phase II randomized noncomparative trial of abiraterone acetate/prednisone (AAP) or AAP and cabazitaxel (AAP + C) in men with mCRPC to address this hypothesis. METHODS: This trial of 81 men with mCRPC determined the radiographic progression-free survival (rPFS), prostate-specific antigen (PSA) progression-free survival, overall objective response, and safety of AAP or AAP + C. Equally allocated patients received AAP followed by switching to cabazitaxel upon radiographic progression (arm 1) or upfront with AAP + C (arm 2). Patients were stratified into high-/low-risk groups by the Halabi nomogram. Real-time assessment of RB status and circulating tumor cell (CTC) analysis to correlate with clinical outcomes was exploratory. RESULTS: Both treatment arms were well-tolerated. Median rPFS in AAP was 6.4 months (95% CI, 3.8 to 10.6) and median overall survival (OS) 18.3 months (95% CI, 14.4 to 37.6), respectively. Fifty-six percent of patients showed ≥50% decline in PSA. Median rPFS in AAP + C was 14.8 months (95% CI, 10.6 to 16.4), and median OS 24.5 months (95% CI, 20.4 to 35.0). There was a ≥50% decline in PSA in 92.1% of men. Neither RB expression in pretherapy tumor biopsy, CTC, or tissue explants identified those who may benefit from AAP + C. CONCLUSION: AAP + C was safe with improved rPFS, OS duration, and a higher proportion of PSA declines. This suggests that AAP + C given earlier rather than sequentially may benefit some men. Further work is needed to identify this population.
Keywords:	controlled study; treatment outcome; disease-free survival; prednisone; clinical trial; disease free survival; antineoplastic agent; prostate specific antigen; phase 2 clinical trial; randomized controlled trial; antineoplastic combined chemotherapy protocols; pathology; prostate-specific antigen; multicenter study; taxoids; abiraterone acetate; taxoid; castration resistant prostate cancer; cabazitaxel; humans; human; male; prostatic neoplasms, castration-resistant
Journal Title:	Journal of Clinical Oncology
Volume:	41
Issue:	32
ISSN:	0732-183X
Publisher:	American Society of Clinical Oncology
Date Published:	2023-11-10
Start Page:	5015
End Page:	5024
Language:	English
DOI:	10.1200/jco.22.02639
PUBMED:	37582240
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85176496201&doi=10.1200%2fJCO.22.02639&partnerID=40&md5=38d3fd2efe7189a8d5b977bf58a1e5a3
Notes:	Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/211434