Addition of docetaxel to initial hormone therapy substantially improves survival in men with metastatic, hormone-sensitive prostate cancer

CHICAGO, IL USA (Press Release) - June 1, 2014

– Summary contains updated data not included in the abstract –

Findings from a federally funded phase III study, E3805, indicate that adding the chemotherapy drug docetaxel to standard hormone therapy extends survival for men with newly diagnosed hormone-sensitive prostate cancer by roughly 10 months. The survival benefit is even greater for the subset of men with extensive disease spread (high-extent disease).

“Hormone therapy has been a standard treatment for prostate cancer since the 1950s,” said lead study author Christopher Sweeney, MBBS, medical oncologist at the Lank Center of Genitourinary Oncology at the Dana-Farber Cancer Institute in Boston, MA. “This is the first study to identify a strategy that prolongs survival in newly diagnosed metastatic prostate cancer. The benefit is substantial and warrants this being a new standard treatment for men who have high-extent disease and are fit for chemotherapy.”

Androgen hormones fuel prostate cancer growth. Hormonal therapy – also called androgen deprivation therapy (ADT) – alone is the standard first-line treatment for hormone-sensitive prostate cancer. Although ADT is effective, the disease eventually becomes resistant to the therapy in most patients. About 30,000 patients die of hormone-resistant prostate cancer in the United States every year. Chemotherapy is typically initiated only after the disease progresses despite ADT.

In this National Cancer Institute-led study, 790 men with newly diagnosed metastatic prostate cancer were randomly assigned to receive either ADT alone or ADT with docetaxel over a period of 18 weeks. Approximately two-thirds of patients had high-extent disease, meaning that the cancer had spread to major organs and/or the patient had bone metastases. When the disease worsened, 45 patients in the ADT plus docetaxel group received additional docetaxel. In the ADT only group, 123 patients received docetaxel at disease progression.

At a median follow-up of 29 months, there were 136 deaths in the ADT-alone group vs. 101 in the ADT plus docetaxel group. The median overall survival was 44 months in the ADT group and 57.6 months in the ADT plus docetaxel group. The relative improvement in median overall survival was even larger among the 520 patients with high-extent disease (32.2 months vs. 49.2 months). The median overall survival for the subset with low-extent disease takes longer to reach as these patients respond better to ADT, and the median survival has not yet been reached.

Docetaxel also delayed disease progression, assessed by either PSA rise or appearance of new metastases or symptom worsening. At one year, the proportion of patients with PSA levels less than 0.2 ng/mL (a PSA level of less than 0.2 is considered a sign of a better remission) was 11.7 percent in the ADT group vs. 22.7 percent in the ADT plus docetaxel group. The median time to clinical progression (new symptoms or metastases detected on a scan) was 19.8 months in the ADT group vs. 32.7 months in the ADT plus docetaxel group.

This new treatment paradigm will entail earlier, multidisciplinary care involving the collaboration of both urologists and oncologists, who both commonly treat men with prostate cancer, Dr. Sweeney said. Follow-up of patients will continue to assess survival benefits for patients with low-extent disease. Quality-of-life data from this study will be analyzed and reported at a later time. This research was supported by the National Cancer Institute, National Institutes of Health.

ASCO Perspective:

“These results demonstrate how we can use ‘old tools’ in new, more powerful ways to improve and extend patients’ lives,” said ASCO president Clifford A. Hudis, MD, FACP. “This study is also a powerful testimony to the importance of National Cancer Institute-led research, as both of these drugs are available in generic form today and this research might have otherwise not been pursued.”

Relevant Links From Cancer.Net, the oncologist-approved cancer information website from the American Society of Clinical Oncology:

• Guide to Prostate Cancer
• Hormone Therapy for Advanced Prostate Cancer
• When the First Treatment Doesn't Work

Relevant links from CancerProgress.Net, the home of ASCO's 50th Anniversary and progress made against 18 of the most common cancers:

• Progress Against Prostate Cancer Timeline
• Progress in Chemotherapy Timeline

Title: 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.
Authors: Christopher Sweeney, Yu-Hui Chen, Michael Anthony Carducci, Glenn Liu, David Frasier Jarrard, Mario A. Eisenberger, Yu-Ning Wong, Noah M. Hahn, Manish Kohli, Nicholas J. Vogelzang, Matthew M. Cooney, Robert Dreicer, Joel Picus, Jorge A. Garcia, Robert S. DiPaola
Dana-Farber Cancer Institute, Boston, MA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; University of Wisconsin Carbone Cancer Center, Madison, WI; Fox Chase Cancer Center, Philadelphia, PA; Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN; Mayo Clinic, Rochester, MN; Comprehensive Cancer Centers of Nevada, Las Vegas, NV; University Hospitals Case Medical Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH; Cleveland Clinic, Cleveland, OH; Division of Oncology, Washington University in St. Louis, St. Louis, MO; Rutgers Biomedical and Health Sciences, New Brunswick, NJ

Background: Docetaxel (D) improves OS of men with mPrCa who have progressed on androgen deprivation therapy (ADT). We aimed to assess the benefit of upfront chemohormonal therapy for metastatic PrCa.

Methods: 1:1 randomization to ADT alone or ADT + D dosed 75mg/m2 every 3 weeks for 6 cycles within 4 month (mos) of starting ADT. Stratification factors: high volume (HV) vs. low volume (LV) disease (HV: visceral metastases and/or 4 or more bone metastases); Anti-androgen use beyond 30 days; Age ≥70 vs. < 70 years; ECOG PS 0-1 vs. 2; Prior adjuvant ADT > 12 vs. ≤ 12 mos; FDA approved drug for delaying skeletal related events.

Key eligibility criteria: suitable organ and neurological function for D; adjuvant ADT ≤ 24 mos and no progression within 12 mos of adjuvant ADT. OS was the primary endpoint and the study was powered to assess for a 33.3% improvement in median OS (80% power and 1-sided alpha=2.5%). Projected median OS for ADT alone: HV-33 mos; LV-67 mos.

Results: 790 men were accrued from 7/28/06 to 11/21/2012: ADT N=393; ADT + D: N=397; balanced for demographic, stratification and disease factors. Median age: 63 years (range: 36 to 91); 98% ECOG PS 0 or 1; 89% Caucasian; 24% prior radiotherapy, 24% prior prostatectomy; HV 64% on ADT and 67% on ADT + D. Data released after 4th interim analysis in Sept 2013 when O’Brien Fleming upper boundary was crossed with 53.1% information. This report reflects 1/16/2014 data with median follow-up of 29 mos with 137 deaths on ADT alone vs. 104 deaths on ADT+D. ADT+D: Grade (G) 3/4 Neutropenic fever: 4%/2%; G3 neuropathy: 1% sensory, 1% motor; 1 death due to treatment (no deaths due to treatment on ADT). Efficacy data is in the table below. After disease progression, 123 pts on ADT alone and 45 pts on ADT + D received docetaxel.

Conclusions: ADT + D improves OS over ADT alone in men with HV mPrCa. Longer follow-up is needed for men with LV mPrCa.

Disclosures: Christopher Sweeney, Consultant or Advisory Role with Sanofi, Honoraria from Sanofi, Research Funding from Sanofi, Other Remuneration from Sanofi; Mario A. Eisenberger, Research Funding from Sanofi; Noah M. Hahn, Consultant or Advisory Role with Sanofi, Honoraria from Sanofi, Research Funding from Sanofi; Jorge A. Garcia, Consultant or Advisory Role with Sanofi, Honoraria from Sanofi, Research Funding from Sanofi; Robert S. DiPaola, Consultant or Advisory Role with Sanofi, Research Funding from Sanofi Research

Funding Source: NIH

American Society of Clinical Oncology (ASCO)

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