The evidence for docetaxel in metastatic castration sensitive prostate cancer comes from three phase III studies.
CHAARTEDr
This study compared six cycles of docetaxel 75 mg/m² 3 weekly, plus androgen deprivation therapy (ADT) versus ADT alone.
Between July 2006 and November 2012, 790 men were randomly assigned to a maximum of 6 cycles of docetaxel plus ADT (n=397) or ADT alone (n=390).
The primary end point was overall survival (OS) and secondary endpoints included time to progressive disease (PD) and time to symptomatic PD. Men were stratified by volume of metastatic disease (high versus low), age, ECOG and prior adjuvant ADT.
STAMPEDEr
Survival data from the STAMPEDE trial, a multicentre, randomised control trial presented at ASCO 2015, showed a clinically and statistically significant improvement from the addition of docetaxel to androgen deprivation therapy in men with high-risk locally advanced or metastatic prostate cancer.
GETUG-AFU 15r
This study compared the addition of nine cycles of docetaxel to ADT versus ADT alone in patients with metastatic castration sensitive prostate cancer. Between October 2004 and December 2008, 385 patients were randomly allocated to receive docetaxel 75 mg/m² 3 weekly, plus ADT (n=192) versus ADT alone (n=193).
The primary endpoint was overall survival (OS) and secondary endpoints were time to clinical progression or death (clinical progression-free survival) and time to PSA progression, clinical progression or death (biochemical progression-free survival).
Efficacy
CHAARTEDr
After a median follow up of 28.9 months there were 101 deaths in the docetaxel plus ADT group compared with 136 deaths in the ADT alone group.
Median OS was 57.6 months for those receiving docetaxel plus ADT group and 44.0 months in those receiving ADT alone (HR 0.61, 95% CI 0.47-0.80; p=0.0003).
For men with high volume metastases (visceral metastases and/or four or more bone metastases) receiving docetaxel plus ADT median OS was significantly improved compared with those receiving ADT alone, 49.2 months and 32.2 months respectively (HR 0.60, 95% CI 0.45-0.81; p<0.0006). Longer follow-up is required for patients with low volume metastatic disease. Subgroup analysis demonstrated benefit in most groups analysed. Median time to clinical progression was 32.7 months in patients receiving docetaxel plus ADT compared with 19.8 months in patients receiving ADT only (HR 0.49, 95% CI 0.37-0.65; p<0.0001). Median time to castrate-resistant prostate cancer was 20.7 months in those receiving the combination therapy compared with 14.7 in those receiving ADT only (HR 0.56, 95% CI 0.44-0.70; p<0.0001).
Overall Survival:r
© New Engl J Med 2015
GETUG AFU 15r
At median follow up of 50 months, median OS was 58.9 months (95% CI 50.8 to 69.1 months) in the docetaxel and ADT group and 54.2 months (95% CI 42.2 months to not yet reached) in the group given ADT alone (HR 1.01, 95% CI 0.75-1.36 p=0.955).
Overall Survival:r
© Lancet Oncol 2013
Updated data presented at ASCO GU meeting 2015r with a median follow up of 82.9 months, the median OS was 46.5 months in the ADT arm and 60.9 months in the ADT +D arm (HR 0.9, 95% CI 0.7 to 1.2; p=0.44). Retrospective analysis using the definition of volume of metastases used in the CHAARTED trial showed a non-significant 4 months increase in OS with ADT+D in the high visceral disease subset of patients.
Toxicity
CHAARTEDr
Grade 3 and 4 adverse events were observed in 16% and 12% of docetaxel with ADT patients respectively. Febrile neutropenia was observed in 6% of patients. Sensory neuropathy was reported in 1% of patients. Toxicity from the ADT alone arm is yet to be reported. There was one treatment related death from chemotherapy (1/397).
© New Engl J Med 2015
GETUG AFU 15r
© Lancet Oncol 2013