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

CHICAGO, IL USA (Press Release) - June 4, 2011 /PRNewswire/ -- This 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. [3] An analysis of a prospective, randomized Phase III trial showing the effectiveness of a drug in extending overall survival in metastatic castration-resistant prostate cancer (mCRPC) also has found that the level of circulating tumour cells (CTCs) - cancer cells that have broken off from the tumour and into the bloodstream - correlated with survival. These initial results have led to the investigation of the use of CTCs as part of a biomarker panel for survival in clinical trials for castration-resistant disease. [4]

More work to prove definitively that levels of CTCs correlates with survival needs to be done, but if ultimately verified, drug companies might be able to use a CTC biomarker to conduct smaller, less costly clinical trials that could lead to faster regulatory approvals. That is "the ultimate goal" of this research into CTCs, said Dr. Howard Scher, a prostate cancer expert at New York's Memorial Sloan-Kettering Cancer Center and the lead author of the Zytiga study. This research is especially important for companies like Johnson & Johnson, Dendreon ( DNDN ) and Medivation ( MDVN ) that are all trying to develop or market new drugs in patients with earlier stages of prostate cancer. These prostate cancer patients tend to live a relatively long time and receive many different drugs before ultimately succumbing to their disease, which makes conducting survival studies challenging and time consuming. [5] According to lead author Howard I. Scher, MD, the D. Wayne Calloway Chair in Urologic Oncology and chief of the Genitourinary Oncology Service at Memorial Sloan-Kettering Cancer Center in New York, studies have linked declining numbers of CTCs with improved overall survival in mCRPC, and in some cases, have been shown to be a more powerful early predictor of survival than PSA among men with prostate cancer. "The ultimate goal of these studies is to develop a biomarker panel that includes CTCs that can be used in Phase III trials instead of a survival endpoint," said Dr. Scher. "This trial was the first to show a survival benefit with the CTC question embedded, and which is part of a formal collaboration with the FDA. Preliminary results show that CTC and lactate dehydrogenase (LDH) are prognostic, confirming previous studies. This trial becomes the basis for a biomarker panel that we will create, which will then be tested prospectively in subsequent trials. [4] "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. [3]

In the prostate cancer study, a team led by Dr. Howard Scher of Memorial Sloan-Kettering Cancer Center in New York looked to see if tests that trap circulating tumor cells -- tiny bits of cancer cells -- could show whether patients are responding to a drug. Johnson & Johnson's Veridex unit has the only approved system for capturing these rare cells, but other teams are working on them. [1] Prostate cancer is very common in older men, who are screened with a test for prostate-specific antigen, or PSA. But that measure can be deceiving, sometimes rising even when a patient is benefiting from a treatment, and vice versa, according to Howard Scher, chief of the Genitourinary Oncology Service at Memorial Sloan-Kettering Cancer Center in New York. [6] One of the problems preventing progress in the fight against cancer is identification of reliable early indicators that may signal whether a treatment can prolong the life of a patient, explained Dr. Howard Scher, a leading cancer researcher from Memorial Sloan-Kettering Cancer Center in New York and the lead author of the study. He presented this work at the 47th annual conference of the American Society of Clinical Oncology (ASCO) that is held this weekend in Chicago. [2]

Data from the study, released today at the at the American Society of Clinical Oncology (ASCO) annual meeting, showed that the prostate cancer patients who had lower levels of circulating tumor cells in their blood following three months of Zytiga therapy was predictive of better response and longer survival. [5] The data, presented at the annual meeting of the American Society of Clinical Oncology, reveal that measuring circulating tumor cells--cancer cells that have fallen off a tumor into the bloodstream--correlates with patient survival. The measuring of such cells could effect the development of future medicines because it may be used instead of measuring overall patient survival in a clinical trial, making such studies shorter, smaller and cheaper. [6]

The studies, presented at American Society of Clinical Oncology meeting in Chicago, are part of the search for biological signals known as biomarkers that can predict which patients are the best match for drugs or give an early indication that treatments are working. The hope is these types of tests will speed effective treatments to patients and shorten clinical trials by giving researchers earlier signals that experimental drugs are working. [1]

Dr. Scher added that while favorable changes in CTC are associated with a better prognosis, the results cannot be used alone to guide treatment decisions for an individual patient. Testing whether changes in CTC can be used to manage individual patients "will require a new, dedicated trial that specifically asks this question." The researchers are continuing their work to define a biomarker panel that is most strongly associated with overall survival in mCRPC. [4] Changes in prostate specific antigen (PSA) have not been shown to be surrogates for survival in prospective trials and cannot be used for regulatory approvals. In the Phase III COU-AA-301 trial, a study of 1,195 patients showed that the drug abiraterone acetate (Zytiga) significantly improved overall survival in mCRPC (15.8 months for those on abiraterone and prednisone versus 11.2 months for those on prednisone and placebo). In this trial, investigators evaluated CTC counts in 972 patients at baseline, and in 723 patients after three months, finding that the abiraterone therapy reduced the number of CTCs, "converting" them from unfavorable (CTC greater than or equal to five) to favorable (CTC less than five) counts. This was predictive of a better prognosis and overall survival as early as four weeks after treatment. [4] A Phase III trial known as COU-AA that involved 1,195 patients showed that the drug Zytiga developed by U.S. laboratory Johnson and Johnson significantly improved overall survival in patients with metastatic castration-resistant prostate cancer. [2] Reference: ASCO 2011 Abstract: LBA4517 Evaluation of circulating tumour cell (CTCs) enumeration as an efficacy response biomarker of overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC): Planned final analysis (FA) of COU-AA-301, a randomized, double-blind, placebo-controlled, phase III study of abiraterone acetate (AA) plus low-dose prednisone (P) post docetaxel. [4] 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 1195 enrolled study patients with metastatic castration-resistant prostate cancer post-docetaxel being treated with either abiraterone acetate plus prednisone or placebo plus prednisone. [3]

Scher's team analyzed a study of 1,195 men with advanced prostate cancer that showed Zytiga, known chemically as abiraterone, extended patients' lives. Scher's team looked to see if there was a correlation between men who fared best in the trial and levels of prostate tumor circulating in their blood. [1] CHICAGO ( TheStreet ) -- A drug's ability to reduce the number of prostate cancer cells circulating in a patient's bloodstream may be an early and reliable signal that the drug is also prolonging survival, according to results from a new study involving Johnson & Johnson's ( JNJ ) prostate cancer drug Zytiga. [5] CHICAGO-- Johnson & Johnson's prostate cancer drug Zytiga showed a slightly improved survival benefit in updated data from a late-stage study that also revealed the potential for a new way to measure the common disease. [6]

A problem plaguing the prostate cancer field is the identification of reliable early indicators that a drug can prolong life. Such indicators, or surrogates, can be used in lieu of a survival endpoint in clinical trials, allowing drugs to be tested in smaller, less costly trials that could potentially enable faster approvals by the U.S. Food and Drug Administration. [4] Researchers are hopeful that a reduction in CTCs could one day be used an early indicator, or surrogate, to replace the survival endpoint now considered the gold standard measure in cancer clinical trials. [5]

In an exploratory, multi-institutional analysis, the researchers administered the vaccine APC8015F to a group of patients from the control arm of three randomized, Phase 3 clinical trials evaluating sipuleucel-T, a similar, FDA-approved cancer vaccine for metastatic castrate resistant prostate cancer. [7] Metastatic prostate cancer patients who received an investigational vaccine made from their own frozen immune cells lived 10 months longer than those not treated with it, researchers from the Kimmel Cancer Center at Jefferson have found. [7]

The number of cancer cells that have broken off from the tumor and reached the blood stream affects the survival rate of patients suffering from advanced stages of prostate cancer, according to a study unveiled here, AFP reported. [2] The team tested the blood of 972 patients at the beginning of the trial, and 723 patients after three months. They found that abiraterone cut the number of circulating tumor cells, and the men who had lower levels of tumor in their blood were more likely to survive. [1] 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. [3] Circulating tumor cells, or CTCs, are cancer cells that have broken away from the tumor and float through the bloodstream. [5]




American Society of Clinical Oncology (ASCO)