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Combination ADT & Taxotere treatment for high risk patients

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Conflicting Randomized Trials on Docetaxel Plus ADT for Hormone Sensitive Metastatic Prostate Cancer (extract from Moshe C Ornstein, MD article - 'Practice Update On-line')

Sweeney's 'CHAARTED' trial reported in May 2014 trial led to a shift in the general approach to the management of patients with newly diagnosed hormone sensitive metastatic prostate cancer.

790 patients with hormone-sensitive metastatic prostate cancer were randomized to to receive androgen-deprivation therapy (ADT) alone or ADT in addition to docetaxel (D).  In all patients, the median overall survival (OS) was 57.6 months in the ADT+D arm compared to 44.0 months in the ADT alone arm. In patients with high-volume disease (visceral metastases and/or four or more bone metastases) the overall survival was significant higher in the ADT+D cohort (49.2 months) than in the ADT alone group (32.2 months).  These results achieved statistical significance, thus leading many to advocate the use of combined ADT+D in patients with newly diagnosed hormone sensitive metastatic prostate cancer.

In late February 2015, Dr Gravis in France reported on the long-term results of a similar phase III trial ('GETUG 15'), androgen deprivation therapy (ADT) plus docetaxel (D) versus ADT alone for hormone-naïve metastatic prostate cancer (PCa)

In this study, 385 patients with  hormone sensitive metastatic prostate cancer were randomized to receive ADT+D vs ADT.  The authors retrospectively reviewed the patients to stratify them into high-volume disease (HVD) vs low-volume disease (LVD), to allow for a more accurate comparison with the CHAARTED trial.  As in CHAARTED, HVD was defined as visceral metastases and/or four or more bone metastases with at least one beyond the pelvis and the vertebral column.  With 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.  In the HVD subset, the median OS was 35.1 months in the ADT alone arm and 39 months in the ADT+D arm.  Dr. Gravis therefore concluded that the  4 months increase in OS with ADT+D was statistically non-significant.

Dr. Eric Small from UCSF and Dr. Evan Yu of the University of Washington followed Dr Gravis's presentation with a discussion and comparison of CHAARTED and GETUG 15 in an attempt to reconcile the seemingly contradictory conclusions.  

The presenters highlighted the following.  There were significantly more patients in the CHAARTED trial, and it was better powered (i.e. had more patients) compared to GETUG 15 to assess for an OS difference between the two groups.  Likewise, the GETUG 15 trial had a significantly higher proportion of patients receiving “salvage” docetaxel, perhaps contributing to the non-significant improvement in OS in those patients.  Additionally, the CHAARTED trial had fewer patients who discontinued treatment early due to toxicity, compared to the GETUG 15 trial (12.5% vs 20%) and it may therefore be a better reflection of the OS in patients who can tolerate this therapeutic approach. 

Overall, the presenters generally agreed that patients with hormone-sensitive metastatic PCa and high volume disease should be treated with docetaxel in addition to ADT, and that the jury is still out regarding patients with low-volume disease.  We await results from additional trials (including STAMPEDE) to help answer this question.

 

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