A Diagnostics & Imaging Week

The National Surgical Adjuvant Breast and Bowel Project (NSABP; Pittsburgh) and Genomic Health (Redwood, California) reported positive results of a study that identified genes associated with prognosis in patients with Stage II and III colon cancer treated with surgery at the 42nd annual meeting of the American Society of Clinical Oncology (ASCO; Alexandria, Virgnia), ongoing this week in Atlanta

Results from this study, which used the same RT-PCR technology Genomic Health applies in its Oncotype DX breast cancer test service, involved analysis of RNA from 270 colon cancers among patients enrolled in studies previously conducted by the NSABP between 1977 and 1984. These included 128 patients with Stage II disease and 142 patients with Stage III disease.

Of the 757 cancer-related and reference genes assessed, 142 genes exhibited an association with recurrence-free interval, or a period of time when the disease has not returned. After controlling for routinely assessed clinical variables, 78 of these genes retained independent significance.

Genomic Health bills its Oncotype DX service as the first multi-gene expression test service commercially available that has clinical evidence validating its ability to predict the likelihood of breast cancer recurrence, the likelihood of patient survival within 10 years of diagnosis and the likelihood of chemotherapy benefit. Oncotype DX has been evaluated in independent studies involving more than 2,600 breast cancer patients, including a large validation study published in The New England Journal of Medicine and a chemotherapy benefit study published in the Journal of Clinical Oncology.

"We have shown, using a standardized quantitative technique, that tumor gene expression at the time of diagnosis is clearly associated with the likelihood of subsequent recurrence in colon cancer patients," said Michael O'Connell, MD, associate chairman of the NSABP and director of the Allegheny General Hospital Cancer Center (Pittsburgh). He said that additional studies will determine whether gene expression analysis can also predict response to adjuvant chemotherapy which, in combination with prognostic information, would enable "more individualized treatment decisions for colon cancer patients."

Lack of clarity using current diagnostic methods may lead to the over-treatment of some patients and the under-treatment of others.

"This early data is very encouraging," said Steven Shak, MD, chief medical officer of Genomic Health. "We have also completed a second study of Stage II and III colon cancer patients which confirmed the prognostic significance of many of the genes identified here. Moving forward, we expect to follow a rigorous clinical development path, as we did with our Oncotype DX test service in breast cancer, conducting multiple studies to develop a reliable test service for predicting recurrence and response to chemotherapy in colon cancer."

NSABP is a not-for-profit, clinical trials cooperative, which includes a network of 3,000 professionals in the U.S., Canada, Europe and Puerto Rico.

In other reports from ASCO:

• Bayer HealthCare, a member of the Bayer Group (Leverkusen, Germany), reported study findings using Bayer Diagnostics' Serum HER-2/neu test that demonstrated metastatic breast cancer (MBC) patients whose serum HER-2/neu levels decreased by less than 20% experienced decreased benefit from trastuzumab-based therapy.

Human Epidermal Growth Factor Receptor 2, or HER-2, is a protein that helps control cell growth.

The data, from a pooled analysis of seven clinical trials in the U.S. and Western Europe of MBC patients who received trastuzumab (with or without chemotherapy), were presented by Suhail Ali, MD, associate professor, Division of Hematology Oncology, Penn State College of Medicine, the Penn State Milton S. Hershey Medical Center (Philadelphia). The Serum HER-2/neu Test from Bayer is the only blood test cleared by the FDA for ongoing monitoring of changes in serum levels of HER-2/neu.

The findings allowed the 307 MBC patients who had the Serum HER-2/neu test before and after trastuzumab-based treatment to be divided into those with a greater than 20% decrease in serum HER-2/neu levels and those with a less than 20% decrease. The patients whose serum HER-2/neu levels decreased by less than 20% had a lower response rate; shorter duration of response; shorter time to progression; and decreased overall survival rate.

"In this analysis, measuring serum HER-2/neu levels provided an early predictor of the outcome of trastuzumab-based therapy in MBC patients," said Allan Lipton, MD, professor of Medicine and Oncology, Penn State College of Medicine, the Penn State Milton S. Hershey Medical Center and a co-author of the pooled analysis. "For instance, patients with greater than 20% decrease in serum HER-2/neu have a decreased disease free and overall survival with trastuzumab based therapies. Patients with greater than 20% should be considered for investigative agents in addition to trastuzumab."

He said that the test "represents a model for the future of personalized medicine in which a serum biomarker is used to direct therapy at an individual level."

The standard method for determining HER-2/neu status is by testing tissue from the primary tumor, usually involving an invasive procedure. A simple blood test to determine serum HER-2/neu levels during the course of therapy is complementary to tissue testing because continuous monitoring of serum concentrations of HER-2/neu allows physicians to follow disease progression and therapy response, thereby guiding ongoing treatment decisions.

• MacroArray Technologies (Atlanta) and GTx (Memphis, Tennessee) reported that MacroArray presented data from its development of a diagnostic test for prostatic intraepithelial neoplasia (PIN) in a general poster session. The poster provides details of MacroArray's development of a novel urine-based diagnostic for high-grade PIN, a premalignant lesion of the prostate.

GTx is supplying to MacroArray urine and serum samples from patients with high-grade PIN enrolled in GTx's Phase IIb and Phase III clinical trials to assist MacroArray in its development and future validation of a noninvasive test for high grade PIN. GTx is conducting a pivotal Phase III clinical trial of Acapodene (toremifene citrate) in a 20 mg dose for the prevention of prostate cancer in men with high grade PIN.

Currently, high-grade PIN can only be diagnosed by prostate needle biopsy. Usually patients undergo a prostate biopsy when they are found to have an elevated serum PSA. Between 8% and 10% of patients who undergo a prostate biopsy will be found to have high grade PIN. Men with high grade PIN have an approximately 50% chance of progressing to prostate cancer within three years and an 80% chance within five to seven years.

In the U.S., 1.1 million men have been diagnosed with high-grade PIN, and it has been estimated that 14 million men may unknowingly harbor the condition. Currently, there are no approved medical treatments for high-grade PIN.

GTx is a biopharmaceutical company dedicated to the discovery, development and commercialization of therapeutics for cancer and serious conditions related to men's health.

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