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Statistical Shortcut Could Speed Evaluation of Prostate Cancer Drugs
PCF-funded ICECaP study identifies earlier clinical trial endpoint that can be used to indicate effectiveness of new treatments
  • Clinical trials of adjuvant therapies used in treating some men with prostate cancer could be completed more quickly by using a “surrogate” endpoint, scientists report
  • The investigators found that metastasis-free survival – how long patients survived without the cancer spreading – was a strong predictor of their overall survival

BOSTON, MA, August 10, 2017 – Scientists say they have validated a “surrogate endpoint” – a reliable statistical shortcut in a clinical trial – that could accelerate testing of new adjuvant therapies aimed at reducing deaths from prostate cancer in patients who were treated for localized disease, but are at risk of relapse.

Christopher Sweeney, MBBS

Reporting in the August issue of the Journal of Clinical Oncology, an international team of researchers, led by Christopher Sweeney, MBBS, of Dana-Farber Cancer Institute, found that measuring metastasis-free survival (MFS) — the length of time before the cancer spread beyond the prostate gland — was a strong predictor of patients’ overall survival (OS), which is the yardstick commonly used in evaluating an adjuvant therapy. The analysis found that OS requires a longer follow-up period to measure than does MFS, and that using MFS as an endpoint could enable more clinical trials to be carried out in a shorter period of time.

Sweeney is the corresponding author representing the Intermediate Clinical Endpoints of Cancer of the Prostate (ICECaP) Working Group, which carried out the study. The ICECaP Working Group comprises more than 50 investigators including statisticians, medical oncologists, urologists, radiation oncologists, and health economists from several dozen institutions around the globe.

Adjuvant therapies are drugs given following initial treatment of prostate cancer with radiation or surgery. They are aimed at ridding the body of cancer cells that survived initial treatment, and may save lives from prostate cancer.

Prostate cancer is a slow growing disease; therefore, it typically takes 10 to 12 years to evaluate an experimental adjuvant therapy for localized prostate cancer in clinical trials that use OS as the endpoint. With a number of new adjuvant drugs undergoing evaluation for this patient group, Sweeney said researchers in the field are seeking ways to get answers quicker and make effective drugs available sooner.

The patients in question are men whose cancer was confined to the prostate gland and were treated with radiation or surgery, but are considered to be at medium or high risk of relapse because of the aggressiveness of other pathological features of their tumor. Adjuvant drugs currently being evaluated include alpharadin, enzalutamide, abiterone, docetaxel, cabazitaxel, and sipuleucel-T vaccine.

The researchers analyzed data from 28 clinical trials involving 28,905 patients.

The analysis found that MFS could serve as a strong and reliable surrogate endpoint in evaluating adjuvant therapies. Using statistical validation models, the researchers showed that the proportion of patients who were metastasis-free at five years closely tracked with the proportion of patients who were alive at eight years following treatment.

As an example of how this would work in practice, Sweeney said that if a drug in a clinical trial achieved a 30 percent reduction in risk of patients developing metastatic disease, that would predict a 25 percent decreased risk of death.

The authors wrote that given this strong correlation, “clinical trials can be designed using MFS as a primary endpoint instead of OS,” resulting in “being able to complete trials in a more expeditious manner.” The idea is to “get a readout of the clinical trial sooner and get drugs to patients sooner,” said Sweeney.

“The discovery of this surrogate endpoint has enormous implications for patients with prostate cancer. Reducing the time needed to conduct clinical trials will accelerate the development of new treatments that can be administered at the earliest stage possible, when the cancer might still be curable,” said Howard Soule, PhD, Chief Science Officer and Executive Vice President of the Prostate Cancer Foundation, which supported the establishment of the ICECaP Working Group and participated in the project. “This project was a huge effort that involved collecting and analyzing an enormous amount of clinical trial data, which required the cooperation of several major co-operative clinical trial groups and pharmaceutical companies. The Prostate Cancer Foundation is very proud of Dr. Sweeney’s leadership and the ICECaP team for conducting this very important project for patients as we continue to work toward defeating prostate cancer once and for all.”

In addition to Sweeney, Dana-Farber investigators on the project included Meredith Regan, ScD, and Wanling Xie, both of the Department of Biostatistics and Computational Biology.

The research was supported by funding provided by a Prostate Cancer Foundation Challenge Award and grants from Astellas Pharma, Medivation, Janssen Pharmaceuticals, Takeda Oncology, Sotio, and Sanofi.

About Dana-Farber Cancer Institute

From achieving the first remissions in childhood cancer with chemotherapy in 1948, to developing the very latest new therapies, Dana-Farber Cancer Institute is one of the world’s leading centers of cancer research and treatment. It is the only center ranked in the top 4 of U.S. News and World Report’s Best Hospitals for both adult and pediatric cancer care.

Dana-Farber sits at the center of a wide range of collaborative efforts to reduce the burden of cancer through scientific inquiry, clinical care, education, community engagement, and advocacy. Dana-Farber/Brigham and Women’s Cancer Center provides the latest in cancer care for adults; Dana-Farber/Boston Children’s Cancer and Blood Disorders Center for children. The Dana-Farber/Harvard Cancer Center unites the cancer research efforts of five Harvard academic medical centers and two graduate schools, while Dana-Farber Community Cancer Care provides high quality cancer treatment in communities outside Boston’s Longwood Medical Area.

Dana-Farber is dedicated to a unique 50/50 balance between cancer research and care, and much of the Institute’s work is dedicated to translating the results of its discovery into new treatments for patients in Boston, and around the world.

About the Prostate Cancer Foundation

The Prostate Cancer Foundation (PCF) is the world’s leading philanthropic organization funding and accelerating prostate cancer research. Founded in 1993, PCF has raised more than $700 million and provided funding to more than 2,000 research programs at more than 200 cancer centers and universities. The PCF global research enterprise now extends to 19 countries and funds a robust research portfolio. PCF advocates for greater awareness of prostate cancer and more efficient investment of governmental research funds for transformational cancer research. Its efforts have helped produce a 20-fold increase in government funding for prostate cancer. For more information, visit www.pcf.org.