A group of leading chemotherapy experts assembled as the Clinical Oncologists for Individualized Therapy (COFIT) refute the findings of the American Society of Clinical Oncology (ASCO) technology assessment panel regarding the use of chemotherapy sensitivity and resistance assays (CSRAs).
The investigators, led by Robert Nagourney, M.D., Larry Weisenthal, M.D., Ph.D., Robert Hoffman, Ph.D. and William Grace, M.D., promote research and application of a specific class of CSRAs that measure drug-induced cell death. These assays have been clinically validated for the selection of optimal chemotherapy regimens for individual patients.
The ASCO panel reported that the use of in-vitro CSRAs to select chemotherapy should be limited to clinical trials and not made available for use in oncologic practice. After reviewing 1,139 published clinical trials, the panel members selected 12 studies that met their criteria and based their recommendations on this limited series. Results of the panel’s findings are reported in this week’s issue of the Journal of Clinical Oncology -- ASCO’s official publication.
CSRAs are in-vitro laboratory analyses that use fresh human tumor biopsies to determine which drugs or combinations of chemotherapeutic agents have the highest likelihood of response for individual cancer patients. Conducted and applied correctly, these analyses enable doctors to individualize and optimize treatments while minimizing the risk of toxicity from chemotherapy.
Assay-directed therapy is based on the premise that each patient’s cancer cells are unique and therefore will respond differently to a given treatment. This is in stark contrast to standard or empiric therapy, in which chemotherapy for a specific patient is based on results from prior clinical studies.
“While we agree with ASCO’s conclusion that CSRA research should be a priority, we take issue with the composition of the panel, the methods for trial selection, the analytic process and, most fundamentally, with the suggestion that the data does not support the utility of these tests,” said Dr. Nagourney, who serves as medical/laboratory director of Rational Therapeutics (Long Beach, Calif.), and has published extensively in the field. “ASCO’s findings could potentially limit patient access to a technology that has proven capable of identifying active treatments.”
Dr. Weisenthal added, ”Both BlueCross/Blue Shield and ASCO demonstrated systemic bias and a lack of expertise in arriving at their conclusions.” Dr. Weisenthal is a 25-year investigator and author in the field. He serves as medical/laboratory director of the Weisenthal Cancer Group (Huntington Beach, CA).
Drs. Nagourney, Weisenthal, Hoffman, and Grace are among a growing number of oncology specialists who support the use of CSRAs that measure drug induced cell death. They assert that the ASCO panel’s analysis is flawed in the following four key areas:
1. Study Selection
ASCO’s recommendations were based on a review of 12 previously published clinical studies, many of which focused on older cell growth assay methods. Drug induced cell death as a surrogate for apoptosis is the most relevant biological measure, and must not be confused with growth-based testing. The panel made no attempt to distinguish cell death from cell growth techniques. While the panel’s criticisms regarding slow turnaround and low evaluability rates may be applicable to the older cell-growth tests, the negative conclusions reached by the panel simply do not apply to newer cell-death assays. In fact, cell death assay results have consistently correlated with response, time to progression and survival.
2. Composition of the panel
Investigators actively working with CSRAs based on cell death were not represented or even consulted by the ASCO panel.
3. Conflicts of Interest