CLINICAL TRIAL Impact of biomarkers on clinical trial risk in breast cancer Jayson L. Parker • Nadia Lushina • Prabjot S. Bal • Teresa Petrella • Rebecca Dent • Gilberto Lopes Received: 29 August 2012 / Accepted: 5 September 2012 / Published online: 25 September 2012 Ó Springer Science+Business Media, LLC. 2012 Abstract We determined the success rate of new drug approval by the US FDA in two breast cancer indications, one of which used a biomarker. This allowed us to assess if biomarkers improved clinical trial risk in breast cancer. We performed a retrospective screening of industry-sponsored drug development programs registered on clinicaltrials.gov from 1998 to 2012 for HER2-positive patients compared to patients that had either failed or had been exposed to anthracycline or taxane, whose first phase I in this indication occurred no earlier than 1998. Compounds not registered on clinicaltrials.gov and studied exclusively outside the US were excluded. Twenty-nine drugs for HER2-positive patients and 28 drugs for anthracycline/taxane-exposed patients met our screening criteria. The overall success rate of new drug development in anthracycline/taxane patients was only 15 %, while in HER2-positive patients it was 23 %. However, HER2-targeted therapies underperformed com- pared to broad acting agents. The cost for clinical trial testing alone, when adjusted for the risk of failure, for HER2-posi- tive breast cancer patients was $199 million, significantly lower than the cost of $274 million for anthracycline/taxane- experienced patients. The use of a validated biomarker, such as HER2, reduced clinical trial risk by as much as 50 % resulting in cost savings of 27 % in advanced and metastatic breast cancer. However, these data have to be evaluated in a context in which studies combining a novel drug with a novel biomarker not yet recognized by the FDA may actually increase clinical trial risk. Keywords Biomarker Á Pharmacogenomics Á Clinical trial Á Risk Á Metastatic breast cancer Á HER2 Introduction Despite major progress in the treatment of breast cancer in the last 20 years, it remains the second leading cause of death among women [1]. Completion of the human genome project brought with it renewed prospects of further ther- apeutic advances in the management of advanced disease [2, 3]. However, the overall trend for new drug approvals has been in decline since 1998 [4, 5] despite rising levels of NIH funding over the same period if unadjusted for infla- tion [6]. Recently, it looks as if new drug approval trends have flattened or increased slightly [7]. In this retrospective study, we quantified the risk of failure for new drugs developed for advanced or metastatic breast cancer and the clinical trial design choices that appear to mitigate such risk in two breast cancer populations: HER2-positive patients and those who were previously exposed to, or had failed, anthracycline or taxane treatment. Our initial find- ings may be useful in reducing the risk of future drug development in breast cancer. It is widely believed that the use of biomarkers could increase the success rate of clinical trial outcomes and thus J. L. Parker (&) Á N. Lushina Á P. S. Bal Department of Biology, University of Toronto, Mississauga, ON, Canada e-mail: jayson.parker@utoronto.ca T. Petrella Á R. Dent Haematology/Oncology, Odette Cancer Center, Sunnybrook Hospital, Toronto, ON, Canada G. Lopes Johns Hopkins Singapore International Medical Centre, Singapore, Singapore G. Lopes Johns Hopkins University School of Medicine, Baltimore, MD, USA 123 Breast Cancer Res Treat (2012) 136:179–185 DOI 10.1007/s10549-012-2247-6