New Brunswick, N.J. – For more than 60 years, the standard of care for patients with prostate cancer fueled by androgen hormones that has spread to other parts of the body has been androgen deprivation therapy (ADT). While the response rate is high, resistance to ADT often occurs. Generally, when ADT is no longer working, chemotherapy is administered for these patients. Research coordinated by the ECOG-ACRIN Cancer Research Group, supported in part by the National Cancer Institute, and published in the current online version of The New England Journal of Medicine (doi: 10.1056/NEJMoa1503747), examined the outcomes of giving the chemotherapy drug docetaxel at the start of ADT. Results showed an increased survival of 13.6 months for patients treated with ADT plus docetaxel than with ADT alone.
The study (known as E3805) was designed by the Eastern Cooperative Oncology Group (ECOG) in 2005. It included 790 patients (median age of 63 years) who were enrolled and randomized from July 2006 to November 2012 to receive either ADT plus docetaxel every three weeks for six cycles or ADT alone. Investigators found that by adding docetaxel at the beginning of the ADT regimen, median overall survival was improved by 13.6 months. Results also showed 27.7 percent of patients in the ADT plus docetaxel arm had a decline in prostate specific antigen (PSA) to less than 0.2 ng/mL at 12 months compared with 16.8 percent for those taking ADT alone.
Lead author Christopher Sweeney, MBBS, associate professor of medicine at Dana Farber Cancer Institute, anticipates these results will be a game changer for therapy guidelines. “The initial results of the study were presented at the American Society of Clinical Oncology (ASCO) meeting in June 2014 and resulted in variable uptake around the globe. Acceptance of the final manuscript in The New England Journal of Medicine along with confirmatory data from the Medical Research Council trial called STAMPEDE presented at ASCO 2015, provides the requisite peer review publication and evidence of reproducibility that will lead to docetaxel plus androgen deprivation therapy being the standard of care for patients fit for chemotherapy with metastatic hormone sensitive prostate cancer. The publication is the final piece required for treatment guidelines to be updated around the globe.”
The study’s senior author Robert S. DiPaola, MD, who is the director of Rutgers Cancer Institute of New Jersey and helped lead the design of the protocol a decade ago when he was the national chairman of the ECOG Genitourinary Committee, says the findings are significant. “When we embarked on this study, early clinical trials and laboratory studies supported the possibility (or hypothesis) that earlier therapy in appropriate patients with docetaxel, used in combination before hormonal resistance occurred, could have greater benefit, but required proof in a definitive study. The effectiveness of the concomitant approach demonstrated in this definitive study also indicates the importance of future clinical studies that seek greater clinical benefit through the study of multi-targeted approaches in earlier disease settings.”
Michael Carducci, MD, AEGON Professor of Prostate Cancer Research and professor of oncology at Johns Hopkins Kimmel Cancer Center, who is also chair of the Prostate Cancer Subcommittee within the Genitourinary Oncology Committee of ECOG-ACRIN agrees. “The survival benefit is clearly significant and supports future efforts to study multiple targeted therapies in earlier disease settings. Additional studies in which we more precisely define the mechanisms of resistance and growth in an individual’s tumor with genomic sequencing, and other means, will be important to maximize the ability to target all the critical pathways to achieve greater success.”
Along with DiPaola, Sweeney and Carducci, the authors include Yu-Hui Chen, Dana-Farber Cancer Institute and ECOG-ACRIN; Glenn Liu, University of Wisconsin Carbone Cancer Center; David F. Jarrard, University of Wisconsin School of Medicine and Public Health and Carbone Cancer Center; Mario Eisenberger, Johns Hopkins University; Yu-Ning Wong, Fox Chase Cancer Center and Temple University Health System; Noah Hahn, Indiana University Melvin and Bren Simon Cancer Center; Manish Kohli, Mayo Clinic; Matthew M. Cooney, University Hospitals Case Medical Center, Seidman Cancer Center; Robert Dreicer, University of Virginia Cancer Center; Nicholas J. Vogelzang, Comprehensive Cancer Centers of Nevada; Joel Picus, Siteman Cancer Center, Washington University School of Medicine; Daniel Shevrin, North Shore University Health System; Maha Hussain, University of Michigan Comprehensive Cancer Center; and Jorge A. Garcia, Cleveland Clinic Taussig Cancer Institute.
Along with the National Cancer Institute, the study was supported in part by Public Health Service Grants CA180820, CA180794, CA180795, CA180802, CA180799, CA180790, CA180853, CA189829, CA180801, CA180888, CA180801, CA31946, CA180821; the National Institutes of Health and the Department of Health and Human Services. The work was also presented in part at the 2014 Annual Meeting of the American Society of Clinical Oncology.
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