At the plenary session of the 2014 ASCO Annual Meeting, Christopher Sweeney, MBBS, presented results of the E3805 trial, Chemohormonal Therapy versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED).1
The trial compared “upfront” chemotherapy plus androgen deprivation therapy (ADT) versus ADT alone in men with metastatic prostate cancer. A planned interim analysis dramatically met the criteria for overall survival significance. Median OS was 57.6 months in the ADT plus docectaxel arm and 44.0 months in the ADT arm (HR 0.61,95% CI:0.47,0.80;P=0.0003).
Of note, the trial inclusion/exclusion criteria was expanded to lower volume patients due to slow accrual (July 2006 to November 2012, 790 patients), where trial sites appeared to be exclusively medical oncology.
Given the juggernaut of interest for all clinicians dedicated to the treatment of advanced PCa, perhaps more progressive urology practices will not only consider infusing docectaxel and/or having enhanced dialogue with their medical oncology colleagues, but also assume greater involvement as trial sites to accrue patients attempting to answer unmet clinical questions regarding sequencing and combinatorial strategies of both oral and infusional therapies. Asssuredly, future chemotherapeutic combinatorial strategies with other already approved oncolytics will be forthcoming.
Furthermore, some urology practices with advanced prostate cancer specialization may want to explore educational initiatives for administering chemotherapy, in addition to other approved infusion therapies.
More importantly, even though approximately 4% to 5% of newly diagnosed patients with prostate cancer in the United States present with radiological confirmed metastatic disease, and the impact of this trial represents a small subset of the annual newly diagnosed patient population, the 17 month median OS supersedes heretofore other U.S. Food and Drug Administration approved castration-resistant prostate cancer (CRPC) therapies by a factor of 4- to 5-fold. The CHAARTED trial results also demonstrated improvement in median time to clinical progression as well as median time to the development of castration resistant status.
The reported adverse event profile was lower than previously seen in CRPC trials (Tax 327/SWOG 9916)2,3; the cohort of patients in these trials were older, had further disease progression and a presumably a more aggressive disease phenotype. It is now encumbent upon the urologic community and all who participate with patients regarding their therapapeutic options to discuss the dramatic survival and disease progression advantages of this therapeutic combination.
Some ongoing considerations now include: (1) a retrospective review of recent newly diagnosed patients with metstatic disease, already initiated with ADT, and thus a present day discussion for 6 cycles of docetaxel; (2) continued awareness of future updated data on those patients with low volume disease; (3) revised consideration for chemohormonal/combination trials for high risk biochemical relapse patients.
The “embarrassment of riches” of therapeutic options for advanced prostate cancer fortunately continues for the benefit of patient care, encouraging us all to strive for lessening the incidence and impact of prostate cancer-specific mortality.
- Sweeney C, Chen Y-H, Carducci MA, et al. Impact on overall survival (OS) with chemohormonal therapy versus hormonal therapy for hormone-sensitive newly metastatic prostate cancer (mPrCa): An ECOG-led phase III randomized trial. J Clin Oncol. 2014;32(5s):(suppl; abstr LBA2).
- Tannock IF, de Wit R, Berry WR, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351(15):1502-1512.
- Petrylak DP, Tangen CM, Hussain MH, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004;351(15):1513-1520.