The evidence for this protocol comes from the results of two randomised, multicentre, multinational, phase III trials- TROPICr and PROSELICA.r
This trial was designed to determine whether cabazitaxel plus prednisone improves overall survival compared with mitozantrone plus prednisone in men with metastatic castration-resistant prostate cancer who had progressed after docetaxel-based chemotherapy.
Between January 2007 and October 2008, 755 patients were randomly assigned to prednisone 10mg daily with either cabazitaxel or mitozantrone intravenously on day one of each 21 day cycle for a maximum of 10 cycles.
The primary end point was overall survival (OS) and secondary endpoints included progression-free survival (PFS), PSA response, PSA progression, objective tumour response, pain response, pain progression and time to tumour progression (TTP).r
The PROSELICAr study, presented in abstract form at ASCO 2016, was a randomised multinational, phase III non-inferiority study comparing 20mg/m2 with 25mg/m2 of cabazitaxel plus prednisolone in patients with metastatic castrate resistant prostate cancer who had progressed after docetaxel. Between April 2011 and December 2013, 1200 patients were randomised to receive either cabazitaxel 20mg/m2 and prednisolone (n=598) or cabazitaxel 25mg/m2 and prednisolone (n=602).
The primary endpoint was overall survival. Secondary endpoints included progression free survival (PFS), safety, PSA, pain and tumour responses and quality of life. This data has yet to be published in a peer-review journal.
Median overall survival was 15.1 months (95% CI 14.1-16.3) in the cabazitaxel group versus 12.7 months (11.6-13.7) in the mitozantrone group.
Median progression-free survival was 2.8 months (95% CI 2.4-3.0) in the cabazitaxel group and 1.4 months (1.4-1.7) in the mitozantrone group (HR 0.74, 95% CI 0.64-0.86, p<0.0001).
Patients receiving cabazitaxel and prednisone also had higher objective tumor response rates (14.4 versus 4.4%) and PSA response rates (39.2 versus 17.8%) and longer median times to tumor progression (8.8 versus 5.4 months) and PSA progression (6.4 versus 3.1 months), but had similar times to pain progression, compared with those receiving mitozantrone and prednisone.r
There was a significant overall survival benefit and progression-free survival in the cabazitaxel group.
© Lancet 2010
Median overall survival was 13.4 months (range 12.19 to 14.88) for the cabazitaxel 20mg/m2 plus prednisolone group compared with 14.5 months (range 13.47 to 15.28) for the cabazitaxel 25mg/m2 plus prednisolone group, upper limit of 98.89% confidence interval (CI) 1.184. The study reached its non-inferiority endpoint. The PSA and ORR were slightly higher in the group receiving cabazitaxel 25mg/m2.
||C20 v C25
|Median OS, mos
||13.4 (12.19 to 14.88)
||14.5 (13.47 to 15.28)
||Upper limit of 98.89% Confidence Interval (CI): 1.184
|Median PFS, mos
||2.9 (2.79 to 3.45)
||3.5 (3.12 to 3.94)
||HR (95% CI): 1.099 (0.974 to 1.24)
|PSA response, %
||29.5 (25.6 to 33.3)
||42.9 (38.8 to 47.1)
The cabazitaxel regimen was significantly more toxic than mitozantrone. The most common toxic effects of cabazitaxel were haematological and the most common non-haematological adverse event was diarrhoea. Higher frequencies of severe (grade 3 or greater) neutropenia (82 versus 58%), severe febrile neutropenia (7 versus 1%), diarrhoea (47 versus 11%, severe in 6 versus less than 1%), and peripheral neuropathy (13 versus 3%) were observed in patients receiving cabazitaxel and prednisone compared with those receiving mitozantrone and prednisone.r
The mitozantrone group had a 74% incidence of total deaths during the study which was higher compared to cabazitaxel which had an occurrence of 61%. However, patients in the cabazitaxel group had a higher risk of death of 5% within 30 days of the last drug dose than the mitozantrone group which had a 2% occurrence. Disease progression was the most common cause of early death among patients receiving mitozantrone, whereas adverse reactions, including neutropenic complications and renal failure, were the most frequent causes of early death among patients receiving cabazitaxel.r
© Lancet 2010
Grade 3-4 adverse events were less in the group receiving cabazitaxel 20 mg/m2 39.7% compared with 54.5% for those in the group receiving 25mg/m2. Grade 4 neutropaenia was less in the groups receiving 20mg/m2 than those receiving 25mg/m221.3% and 48.6% respectively and neutropaenic infection/sepsis was 2.2% and 6.1%.