Data presented at the 47th American Society of Clinical Oncology (ASCO) annual meeting demonstrate the potential of circulating tumor cells (CTC) as a biomarker for metastatic prostate cancer clinical trials.

Circulating tumor cells are cancer cells that have detached from the tumor and are found at extremely low levels in the bloodstream. The value of capturing and counting CTCs is evolving as more research data is gathered about the utility of these markers in monitoring disease progression and potentially guiding personalized cancer therapy.

Phase III Study
The study represents the first randomized, double-blind, placebo controlled Phase III trial to evaluate CTCs as a potential biomarker for overall survival. Biomarkers are of scientific interest as, if validated, they could be used as a surrogate for a clinical endpoint and may help accelerate the clinical trial process.

Results of the study titled, “Evaluation of circulating tumor cell (CTC) enumeration as an efficacy response biomarker of overall survival (OS) in metastatic castration resistant prostate cancer (mCRPC)” indicated that pre-treatment, CTCs and lactate dehydrogenase (LDH), both alone and in combination, were prognostic biomarkers, while baseline prostate-specific antigen (PSA) was not. Following the start of treatment, CTC counts were measured at four, eight and 12 weeks. The data suggest that changes in CTC counts can predict overall survival during treatment. Data also indicated LDH was strongly associated with survival.

Study Design
The CTC analysis was conducted to determine if CTCs could be used as a surrogate for overall survival. It was performed in 900 of the 1,195 enrolled study patients with metastatic castration-resistant prostate cancer post-docetaxel being treated with either abiraterone acetate (Zytiga?, Centocor Ortho Biotech, Inc.) plus prednisone or placebo plus prednisone. CTCs were counted (cells/7.5 mL) along with other biomarkers including PSA, LDH, hemoglobin, alkaline phosphatase at screening and baseline and post-baseline at four, eight and 12 weeks. Analyses were conducted for these biomarkers individually and collectively.

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Shorter Trials
“Establishing CTCs as a biomarker or part of a biomarker panel that is a surrogate-endpoint for survival would be an important step toward our goal of enabling shorter trials and more rapid drug approvals in prostate cancer,” said Howard Scher, M.D., the lead author of the study and chief of the genitourinary oncology service at the Sidney Kimmel Center for Urologic and Prostate Cancers at Memorial Sloan-Kettering Cancer Center.

“As the only device with regulatory clearance to capture and count CTCs, we are excited that the data substantiates the prognostic value of Cellsearch?,” said Robert McCormack, Ph.D. and Head of Technology Innovation at Veridex, LLC.

Routine blood test
Cellsearch is the first and only regulatory-cleared in vitro diagnostic test to capture and count CTCs to determine the prognosis of patients with metastatic breast, colorectal or prostate cancer. The test can be administered at any time during the course of therapy as a routine blood test. It is used in combination with other tests and a clinician’s assessment, to provide a more complete picture of a patient’s prognosis.

“We look forward to further investigating the potential predictive benefit of CTCs in metastatic prostate cancer clinical trials as there are limited ways of assessing therapeutic benefit in this disease, especially when it has metastasized to the bone,” McCormack noted.

Additional studies are underway to further validate CTCs as a surrogate endpoint in metastatic prostate cancer studies.

Substantiating In Vitro Diagnostic Use of Cellsearch?
An independent study investigating the in vitro diagnostic use of CTC testing found that the number of CTCs in the blood may help physicians more reliably assess treatment benefit for patients with metastatic breast cancer. The study, a large-scale retrospective analysis using blinded data to create a pooled dataset of 841 patients from cancer centers around the world, found that CTC count at or above the threshold of five was reliably associated with disease progression. Further, the predictive value of CTCs was not affected by treatment type (chemotherapy, endocrine therapy, biologic therapy), tumor type (hormone receptor positive/negative, HER2 positive/negative), or sites of disease involvement. The study was lead by Minetta Liu, M.D., Georgetown Lombardi Comprehensive Cancer Center and will be presented during a poster session on Monday, June 6th, 2011.

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