Cabazitaxel in the treatment of metastatic castration-resistant prostate cancer: patient selection and special considerations

Figures & data

Table 1 FIRSTANA (NCT01308567) side effect profile of docetaxel vs cabazitaxel as first-line treatment in mCRPC

TEAEs >5%	Docetaxel 75 mg/m^2 (%)		Cabazitaxel 25 mg/m^2 (%)
	All grades	Grade 3/4	All grades	Grade 3/4
Febrile neutropenia	8.3	8.3	12	12
Neutropenic infection	4.9	4.1	6.1	5.9
Diarrhea	37	2.3	49.9	5.6
Stomatitis	13.7	0.8	6.6	0.3
Hematuria	3.6	0.3	25.1	3.6
Peripheral neuropathy	25.1	2.1	12.3	0
Peripheral edema	20.4	1.6	7.7	0.3
Alopecia	39	0	13	0
Nail disorders	9	0.3	0.8	0

Abbreviations: mCRPC, metastatic castration-resistant prostate cancer; TEAEs, treatment-emergent adverse events.

Table 2 Recently completed clinical trials of cabazitaxel in mCRPC

NCT number	Phase	Description	Results
Single-agent cabazitaxel in mCRPC
NCT01254279	III	UK EAP to assess quality of life and safety data on cabazitaxel 25 mg/m^2 in mCRPC previously treated with docetaxel^Citation8	Almost 1/3 of patients completed ≥10 cycles in the UK EAP. QOL was stable with trends to improved EQ-5D and VAS scores. Improved or stable pain was observed in the majority of patients continuing therapy
NCT00417079	III	TROPIC: cabazitaxel vs mitoxantrone in mCRPC previously treated with docetaxel^Citation6	Updated cabazitaxel prolongs OS at 2 years vs mitoxantrone and has low rates of peripheral neuropathy. Palliation benefits of cabazitaxel were comparable to those of mitoxantrone
NCT01649635	IV	PROSPECTA: to assess effectiveness of prophylactic treatment of hematological complications (grade ≥3 neutropenia) resulting from cabazitaxel treatment in mCRPC previously treated with docetaxel	Not posted
NCT02074137	IV	Evaluation of safety of cabazitaxel in patients with mCRPC previously treated with docetaxel	Not posted
NCT02441894	IV	PEGAZUS: assess tolerability of cabazitaxel with primary prophylaxis PEG-G-CSF in mCRPC previously treated with docetaxel	Not posted
NCT01324583	I	Dose-escalation study with cabazitaxel and prednisolone in patients with hormone refractory prostate cancer previously treated with docetaxel	Not posted
Cabazitaxel dosing in mCRPC
NCT01308580	III	PROSELICA: cabazitaxel at 20 vs 25 mg/m^2 with prednisone for the treatment of mCRPC^Citation10	Cabaztiaxel 20 mg/m^2 demonstrates noninferiority for OS compared to Cabaztiaxel 25 mg/m^2 and an improved overall safety profile
NCT01541007	II	ConCab: assess tolerability of cabazitaxel 25 mg/m^2 every three weeks vs 10 mg/m^2 for 5 consecutive weeks of a 6-week cycle	Not posted
NCT01518283	II	Study of weekly cabazitaxel for unfit mCRPC^Citation12	Cabazitaxel 10 mg/m^2 weekly is tolerable and effective in unfit patients and results in OS of 14.2 months
NCT01558219	II	Safety and efficacy of biweekly dosing of cabazitaxel in second line treatment of mCRPC^Citation34	Cabazitaxel 16 mg/m^2 biweekly without G-CSF is tolerable with 16% neutropenia and 1.7% neutropenic infection
Sequencing of single-agent cabazitaxel in mCRPC
NCT01718353	II	TAXYNERGY: explore the benefit of an early switch from docetaxel to cabazitaxel and vice versa in mCRPC who do not achieve ≥30% PSA decline from baseline by cycle 4 and correlated with CTCs19	PSA reduction in 55.6% of patients compared to historic rate of 45.4% in TAX327. Nearly 90% of men with progressive chemo-naive mCRPC have detectable CTCs with higher CTC counts associated with adverse prognostic variables. Lower percent of nuclear AR was associated with visceral metastases, suggesting that progressive visceral CRPC may be less AR driven. Decrease in ARNL on day 8 of taxane treatment correlates with PSA response
NCT01576029	II	SWITCH: compare the continuation of treatment with docetaxel vs switching to cabazitaxel regarding the time to PSA progression	Not posted
Cabazitaxel with AR agent in mCRPC
NCT01511536	I and II	Determine MTD and efficacy of cabazitaxel with abiraterone in mCRPC progressed on docetaxel^Citation28	Phase I: MTD-cabazitaxel 25 mg/m2 every 21 days with abiraterone 1,000 mg daily; Phase II: statistically significant PSA reduction in 46% of patients
NCT01845792	II	Study of cabazitaxel with or without abiraterone/prednisone in mCRPC	Not posted
Cabazitaxel with other agents in mCRPC
NCT01513733	I	CATCH: determine safety and MTD of tasquinimod in combination with cabazitaxel in men with chemorefractory mCRPC27	MTD established at Cabaztiaxel 25 mg/m2 every 3 weeks with tasquinimod 0.5 mg daily with a 3-week lead-in at 0.25 mg daily
NCT01505868	II	Study of cabazitaxel with or without carboplatin (AUC 4) in patients with mCRPC29	Combination with significantly better PFS overall (7 vs 4.6 m) and in aggressive subtype (8 vs 4.5 m)
NCT01578655	III	AFFINITY: determine if addition of curtisen to cabazitaxel/prednisone enhances OS and PFS in mCRPC26	No statistically significant improvement in OS

Abbreviations: AR, androgen receptor; ARNL, AR nuclear localization; AUC, area under the curve; CRPC, castration-resistant prostate cancer; CTCs, circulating tumor cells; EQ-5D, Descriptive system of health-related quality of life states consisting of five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression); G-CSF, granulocyte colony stimulating factor; m, months; mCRPC, metastatic castration-resistant prostate cancer; MTD, maximum tolerated dose; OS, overall survival; PEG, polyethylene glycol; PFS, progression-free survival; PSA, prostate specific antigen; QOL, quality of life; UK EAP, United Kingdom Early Access Program; VAS, visual analogue scale.

Table 3 Ongoing clinical trials of cabazitaxel in prostate cancer

NCT number	Phase	Description
Cabazitaxel in high risk or locally advanced disease
NCT01952223	III	PEACE2: assess effect of neoadjuvant cabazitaxel and pelvic XRT with ADT in high-risk localized prostate cancer
NCT01420250	I	Weekly cabazitaxel with IMRT and ADT in locally advanced prostate cancer
NCT01978873	III	SenciCab: cabazitaxel + ADT vs ADT alone in metastatic or high-risk disease
NCT02543255	II	ACDC trial: neoadjuvant cabazitaxel and abiraterone with ADT in high-risk prostate cancer
Cabazitaxel sequencing in mCRPC
NCT01308567	III	FIRSTANA: cabazitaxel vs docetaxel both with prednisone as first line in patients with mCRPC
NCT02044354	III	CABA-DOC: patient preference between first-line cabazitaxel vs docetaxel in mCRPC
NCT02844582	II	Cabazitaxel/prednisone as first line therapy in mCRPC
NCT02254785	II	Compare the clinical benefit of cabazitaxel vs abiraterone or enzalutamide in poor prognosis mCRPC patients
NCT02485691	IV	CARD: compare cabazitaxel vs AR-directed agents in mCRPC previously treated with docetaxel and who rapidly failed a prior AR agent
NCT02512458	II	CABA-BONE: explore the effect of cabazitaxel on survival pathways and androgen signaling in the tumor microenvironment (bone marrow) of patients with mCRPC
NCT02903160	II	PRINT: determine the clinical benefits of using a rapidly cycling, non-cross-reactive regimen of FDA-approved prostate cancer therapeutic agents in the management of CRPC
Alternate dosing of cabazitaxel in mCRPC
NCT02961257	III	CABASTY: safety of biweekly cabazitaxel at 16 mg/m^2 vs triweekly cabazitaxel at 25 mg/m^2 in elderly mCRPC patients previously treated with docetaxel
Cabazitaxel combined with AR agent in mCRPC
NCT02218606	II	Determine pathologic effects of abiraterone with or without cabazitaxel on mCRPC tissue
NCT02522715	I and II	Assess safety/tolerability of enzalutamide and cabazitaxel combination in mCRPC
NCT03110588	I	PACE: determine the feasibility and recommended dose of the combination of four drugs (prednisone, abiraterone, and cabazitaxel and enzalutamide as first-line therapy for mCRPC
Cabazitaxel with other agents in mCRPC
NCT01594918	I	CAMP: assess safety and dosing of cabazitaxel with mitoxantrone and prednisone in mCRPC
NCT02703623	II	DyanMo: safety and effectiveness of drug combinations in mCRPC of apalutamide and abiraterone with carboplatin and ipilimumab or cabazitaxel
NCT03043989	I	Cohorts of docetaxel or cabazitaxel in combination with potent CYP3A4 inhibitor clarithromycin
Biomarker assessment with cabazitaxel
NCT03050866	II	CABAV7: cabazitaxel in mCRPC patients with AR-V7-positive CTCs
NCT03101046	II	TACTIK: treatment of mCRPC patients according to CTC kinetics

Abbreviations: ADT, androgen deprivation therapy; AR, androgen receptor; AR-V7, AR splice variant 7; CRPC, castration-resistant prostate cancer; CTCs, circulating tumor cells; CYP3A4, cytochrome P450 3A4; FDA, US Food and Drug Administration; IMRT, intensity modulated radiation therapy; mCRPC, metastatic castration-resistant prostate cancer; XRT, radiation.

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