title: Impact of biomarkers on clinical trial risk in breast cancer.
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 compared to broad acting agents. The cost for clinical trial testing alone, when adjusted for the risk of failure, for HER2-positive 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.
authors.affiliation: Department of Biology, University of Toronto, Mississauga, ON, Canada. jayson.parker@utoronto.ca
authors.forename: Jayson L
authors.initials: JL
authors.lastname: Parker
authors.forename: Nadia
authors.initials: N
authors.lastname: Lushina
authors.forename: Prabjot S
authors.initials: PS
authors.lastname: Bal
authors.forename: Teresa
authors.initials: T
authors.lastname: Petrella
authors.forename: Rebecca
authors.initials: R
authors.lastname: Dent
authors.forename: Gilberto
authors.initials: G
authors.lastname: Lopes
mesh_terms: D018943:Anthracyclines / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000191:economics / Q000378:metabolism; D001952:Bridged-Ring Compounds / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003362:Cost-Benefit Analysis; D017277:Drug Approval / Q000191:economics*; D005260:Female; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D012189:Retrospective Studies; D043823:Taxoids / Q000627:therapeutic use; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D018943:Anthracyclines; D014408:Biomarkers, Tumor; D001952:Bridged-Ring Compounds; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; C080625:taxane; C508053:ERBB2 protein, human