Phase I/II trial of cabazitaxel plus abiraterone in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel and abiraterone.
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Date
2017-01-01ICR Author
Author
Massard, C
Mateo, J
Loriot, Y
Pezaro, C
Albiges, L
Mehra, N
Varga, A
Bianchini, D
Ryan, CJ
Petrylak, DP
Attard, G
Shen, L
Fizazi, K
de Bono, J
Type
Journal Article
Metadata
Show full item recordAbstract
BACKGROUND: Abiraterone and cabazitaxel improve survival in patients with metastatic castration-resistant prostate cancer (mCRPC). We conducted an open-label phase I/II trial of cabazitaxel plus abiraterone to assess the antitumor activity and tolerability in patients with progressive mCRPC after docetaxel (phase I), and after docetaxel and abiraterone (phase II) (NCT01511536). PATIENTS AND METHODS: The primary objectives were to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of cabazitaxel plus abiraterone (phase I), and the prostate-specific antigen (PSA) response defined as a ≥ 50% decrease confirmed ≥3 weeks later with this combination (phase II). RESULTS: Ten patients were enrolled in the phase I component; nine were evaluable. No DLTs were identified. The MTD was established as the approved doses for both drugs (cabazitaxel 25 mg/m2 every 3 weeks and abiraterone 1000 mg once daily). Daily abiraterone treatment did not impact on cabazitaxel clearance. Twenty-seven patients received cabazitaxel plus abiraterone plus prednisone (5 mg twice daily) in phase II. The median number of cycles administered (cabazitaxel) was seven (range: 1-28). Grade 3-4 treatment-emergent adverse events included asthenia (in 5 patients; 14%), neutropenia (in 5 patients; 14%) and diarrhea (in 3 patients; 8%). Nine patients (24%) required dose reductions of cabazitaxel. Of 26 evaluable patients, 12 achieved a PSA response [46%; 95% confidence interval (CI): 26.6-66.6%]. Median PSA-progression-free survival was 6.9 months (95% CI: 4.1-10.3 months). Of 14 patients with measurable disease at baseline, 3 (21%) achieved a partial response per response evaluation criteria in solid tumors. CONCLUSIONS: The combination of cabazitaxel and abiraterone has a manageable safety profile and shows antitumor activity in patients previously treated with docetaxel and abiraterone.
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Subject
Humans
Neoplasm Metastasis
Neoplasm Recurrence, Local
Disease Progression
Taxoids
Androstenes
Prostate-Specific Antigen
Antineoplastic Combined Chemotherapy Protocols
Disease-Free Survival
Treatment Outcome
Maximum Tolerated Dose
Aged
Middle Aged
Male
Kaplan-Meier Estimate
Prostatic Neoplasms, Castration-Resistant
Docetaxel
Research team
Prostate Cancer Targeted Therapy Group
Treatment Resistance
Language
eng
License start date
2017-01
Citation
Annals of oncology : official journal of the European Society for Medical Oncology, 2017, 28 (1), pp. 90 - 95
Publisher
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