There has been a great deal of hype following a plenary presentation at the 2014 American Society of Clinical Oncology (ASCO) Annual Scientific Meeting in Chicago in June 2014.
Chris Sweeney presented the results of the E3805 “CHAARTED” trial, which looked at the effects of adding docetaxel chemotherapy at the time of commencement of androgen deprivation therapy (ADT) in men with metastatic prostate cancer. The standard of care prior to this study was to use ADT alone in this setting as it is highly effective although not curative. Docetaxel was shown in key papers published 10 years ago to be of benefit in men with castrate-resistant prostate cancer, ie cancer that had already progressed despite hormonal therapy that had resulted in castrate serum levels of androgens. Docetaxel was well tolerated in that more advanced setting, and led to an improvement in median survival of about two months. It also had other benefits in terms of symptom control, PSA and objective tumour responses.
The CHAARTED trial broke new ground in commencing docetaxel far earlier than it is usually used, and the outcomes were striking. A total of 790 men entered the study and were randomised 1:1 to receive ADT plus 6 cycles of docetaxel versus ADT alone. Key eligibility criteria were: documented evidence of metastatic prostate cancer; very limited or no prior androgen deprivation therapy; good performance status; no prior docetaxel. The primary endpoint of the study was overall survival and there were numerous secondary endpoints. The study was reported after a planned interim analysis in October 2013 showed that pre-specified criteria for significance and release of data had been met. The ASCO presentation included data as at January 2014 with a median followup of 29 months.
The key messages are:
- The treatment was safe and well tolerated overall. Almost all men received all six cycles and 74% had no dose modifications. Adverse events of more severe grades occurred in very few patients.
- Overall survival for the whole study population was significantly improved, with a hazard ratio for death of 0.61 (0.47-0.80, P=0.0003) and median survival of 57.6 months for the docetaxel plus ADT group versus 44.0 months for the ADT alone group. That is an improvement in median survival of 13.6 months, far more than what is seen when docetaxel is used in the castrate-resistant setting.
- The effect was even more striking in the group with “high volume” disease, defined as visceral metastases or 4 or more bone metastases including one beyond the pelvis and vertebral column. In the high volume subgroup, the hazard ratio for death was 0.60 (0.45-0.81, P=0.0006) with median survival of 49.2 months for the docetaxel plus ADT group versus 32.2 months for the ADT alone group. That is an improvement of 17 months. A similar trend is seen for the low volume subgroup but longer followup is required for them.
- Benefits were seen for the secondary endpoints also.
- Note: the study has not yet been published and so has not yet undergone formal peer review.
These results were described as “unprecedented” and this is true: no other treatment except for ADT itself has shown such a significant effect on survival in metastatic prostate cancer. The results are certain to change practice around the world including Australia. At present docetaxel is not approved in Australia for this indication and is reimbursed only for treatment of castrate-resistant disease, so it cannot currently be prescribed in the hormone-sensitive setting for PBS reimbursement. However, the drug is now generic and hence cheap and we expect uptake of these results into clinical practice to occur very rapidly. Patients with newly diagnosed hormone-sensitive prostate cancer should be reviewed and discussed in a multidisciplinary setting and addition of docetaxel to ADT should be one of the considerations.
Professor Ian Davis is Professor of Medicine and Head of the Eastern Health Clinical School, Monash University and Chair of ANZUP. ANZUP are holding a Community Forum on 13th July – click here for more information and here to read Ian’s synopsis of what the CHAARTED trial means for patients.