A retrospective analysis of phase 1 oncology studies that used biopsy-derived pharmacodynamic biomarkers, could not draw a correlation between subsequent drug development and biopsy sample collection.
A retrospective analysis of about 72 phase 1 oncology studies, conducted between 2003 and 2010, that used biopsy-derived pharmacodynamic biomarkers, could not draw a correlation between subsequent drug development or drug use and biopsy sample collection.
Starting with literature review that identified nearly 5000 phase 1 oncology trials conducted during the 7-year period, the authors narrowed their study to 72 trials that use a biomarker. About 1873 biopsies were documented in the 72 studies, and only 12 of these studies reported having a significant biomarker result. Only 4 of the 12 studies were referenced by subsequent publications and the maximum tolerated dose from those studies was applied in future drug development. An important consideration is that 14 of the 72 studies did not mention the number of biopsies that were performed, which would mean that 1873 is possibly a lower estimate of the total number of biopsies conducted in these studies.
According to senior study author Mark Ratain, MD, professor of medicine at the University of Chicago, their study “calls into question the increasing use of such biomarkers in phase 1 studies. The process has had little or no impact on drug development or dose decisions.” He went on to describe the tricky situation that patient’s face: if they want to receive an investigational drug, they are forced to consent to sharing their tissue samples. Hailing action from institutional review boards that review these studies, Ratain said, “Institutional review boards should consider whether such exploratory tissue sampling is even ethical.” He went on to suggest that the primary objective of trials that collect biopsy samples should not be pharmacodynamic evaluation, rather, it should ascertain the effect of drug on the biomarker.
Published in the Journal of Clinical Oncology, the study also draws attention to the unnecessary cost associated with collecting and analyzing biopsy samples that cannot be associated with fruitful outcomes. Depending on the site of the tissue, a biopsy could cost a health system anywhere from $1000 to $10,000. One such study analyzed the Medicare utilization rates for biopsies in lung cancer patients and found that between 2009 and 2011, biopsy costs in lung cancer patients with an abnormal chest CT scan who had negative biopsies touched $16.5 million. The average cost of a biopsy in these patients was $3558. A core-needle biopsy in breast cancer patients is estimated at $483.