Extra Biopsies in Clinical Trials Often Have No Impact on Drug Dose or Use in Cancer Treatments

Extra biopsies performed solely to study the pharmacodynamics of a new anticancer drug have no impact on subsequent drug development or on how physicians use these new drugs to treat future patients, according to a study published in the Journal of Clinical Oncology (doi:10.1200/JCO.2015.63.6126).

Researchers studying the newest anticancer drugs often perform extra biopsies solely for the purpose of trying to understand what a new anticancer drug does to the tumor. Such biopsies are incorporated into studies sponsored by both the pharmaceutical industry and the National Cancer Institute, and are often mandatory in government-sponsored phase 1 clinical trials.

The researchers, cancer specialists from the University of Chicago in Illinois, identified 72 phase I studies of novel cancer drugs published between 2003 and 2010 that included nearly 2000 nondiagnostic biopsies of solid tumors. The biopsy samples were used to study the biochemical and physiological effects and mechanisms of action of new drugs.

The researchers focused on all studies published over the 8-year period that involved procurement of an invasive, nondiagnostic, posttreatment tumor biopsy. The 72 studies led to 1873 biopsies; although this figure is probably low as 14 studies did not mention the number of biopsies obtained. The researchers calculated the average cost of a biopsy for this purpose to be approximately $6675 per patient.

Only 12 studies (17%) reported a statistically significant biomarker result. Only 5 subsequent published reports of phase 2 or phase 3 trials of the same drugs mentioned the previous biomarker studies.

Information from the biopsies was not used to guide drug dose in any subsequent studies. Recommendations were to use the maximum tolerated dose based on overall toxicity rather than the drugs' biologic activity as determined from biopsy samples.

Many studies include the extra biopsies in the protocol, and patients give their consent for the full extent of the study to receive the investigational treatment, even though the biopsies in the studies examined in this review provided no research or clinical benefit.

Mandatory biopsies would be reasonable if they were of scientific value. Biopsy studies that are the primary end point are ethical, if appropriately designed

"Our findings argue that the use of invasive biopsies for the purpose of pharmacodynamics should be limited to clinical trials in which the primary objective is to ascertain the effect of the drug(s) on the biomarker," the researchers concluded. "Given the risk and the cost, this issue requires further study."

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