You are here
Re: Chemohormonal Therapy in Metastatic Hormone-sensitive Prostate Cancer
European Urology 69 (2016) 174-178
Sweeney et al report the results of the CHAARTED trial, in which 790 patients were randomized between androgen deprivation therapy (ADT) alone and ADT in combination with six courses of docetaxel (75 mg/m2 every 3 wk, with premedication of 8 mg dexamethasone at 12, 3, and 1 h before). Daily prednisone was not required. The evaluation was based on an intention-to-treat plan analysis. With a median follow-up of 28.9 mo, it was demonstrated that the median overall survival was 13.6 mo longer in the combination group (57.6 vs 44.0 mo). In particular, patients with high-volume disease (presence of visceral metastases or four or more bone lesions with one or more beyond the vertebral bodies and pelvis) were found to have better median overall survival of 17 mo in the combination arm (49.2 vs 32.2 mo).
Prostate-specific antigen (PSA) responses at 6 and 12 mo (<0.2 ng/ml) were worse in the ADT-alone arm, and the median time to castrate-resistant prostate cancer (CRPC) was 8.5 mo longer in the combination arm.
Approximately 86% of the patients assigned to docetaxel completed the six courses, and the toxicity seen with docetaxel was moderate (2% grade 3 or 4 allergic reaction, 4% grade 3 fatigue, and approximately 1% grade 3 diarrhea, stomatitis, motor neuropathy, and sensory neuropathy).
In the ADT-alone arm, 287 patients developed CRPC; 137 received docetaxel, and 104 received abiraterone or enzalutamide.
This long-awaited publication will change clinical practice for patients with newly diagnosed hormone-naïve metastatic prostate cancer, especially since the results of the STAMPEDE trial were also presented recently at the American Society of Clinical Oncology 2015 meeting and confirmed the results of CHAARTED . In the STAMPEDE trial, 1184 patients with locally advanced and metastatic disease received ADT alone, and 592 received combination therapy. The median overall survival was extended by 10 mo if ADT was combined with docetaxel, from 67 to 77 mo; in the patients with metastatic disease, the median overall survival improved by 22 mo, from 43 to 65 mo. The recent discussion of why this overall survival advantage of combining ADT with docetaxel was not found in the GETUG-AFU 15 study must be explained by the inclusion of a different M+ patient population and access to the new second-line treatments . What these trials demonstrate is that the primary end point of overall survival in this disease entity perhaps should be challenged now that many active subsequent treatments are available, and it will be impossible to evaluate these options in every individual patient.
A problem that remains is the definition of high-volume disease. In the CHAARTED study, approximately 15% had visceral disease, but it is not shown whether all patients had a computed tomography scan or magnetic resonance imaging before inclusion.
The subgroup analysis showed, for all groups, a benefit for the combination arm, but it was interesting to observe that patients not receiving antiandrogen treatment at the start of ADT fared a bit worse. The same observation was made for Eastern Cooperative Oncology Group (ECOG) performance status (PS); those patients with symptoms due to prostate cancer (ECOG PS 1 or 2) did better on combination treatment than patients with PS 0.
We have to realize that these are subgroup analyses, thus no definite conclusions can be drawn. This publication will certainly have an impact on the different prostate cancer guidelines. Particularly for patients with high-volume disease, the combination of ADT with docetaxel will be the standard of care because the improvement in overall survival is unprecedented. However, these patients will progress at some time point to castrate-resistant disease. What will then be the treatment of choice? Rechallenge with docetaxel or start with cabazitaxel, abiraterone, or enzalutamide?
Conflicts of interest
The author has nothing to disclose.
-  N.D. James, M.R. Sydes, M.D. Mason, et al. Docetaxel and/or zoledronic acid for hormone-naïve prostate cancer: first overall survival results from STAMPEDE (NCT00268476) [abstract 5001]. J Clin Oncol. 2015;33(Suppl)
-  G. Gravis, K. Fizazi, F. Joly, et al. Androgen-deprivation therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU 15): a randomised, open label, phase 3 trial. Lancet Oncol. 2013;14:149-158 Crossref
Department of Urology, Academic Medical Center, Amsterdam, The Netherlands
⁎ Department of Urology, Academic Medical Center, Meibergdreef 9, Amsterdam, 1105 AZ, The Netherlands.
© 2015 Published by Elsevier B.V.