title: Patterns in target-directed breast cancer research.
abstract: We undertake an analysis of ongoing BC targeted therapy trials registered to CT.gov to describe patterns of ongoing clinical research, highlight gaps in current research programs and identify ways of optimizing ongoing initiatives. A search of clinicaltrials.gov was conducted on September 4, 2013 to identify ongoing randomized phase II and III trials of targeted therapies in BC. A total of 280 trials were analyzed, the majority conducted in either human epidermal growth factor receptor 2 (HER2)-positive (n = 79, 28.2 %) or hormone receptor (HR)-positive (n = 104, 37.1 %) populations. Less than half of all trials were conducted in populations selected to match the agent under investigation (n = 126, 45 %). HER2-directed therapy is the single most investigated class of targeted agents (n = 73, 26.1 %), but trials investigating anti-angiogenic agents are also common (n = 49, 17.5 %). The most common new classes of agents under investigation in HR-positive and triple negative (TN)/BRCA-positive disease, are non-receptor protein kinase-inhibitors (n = 12; 11.5 %) and poly (ADP-ribose) polymerase inhibitors (n = 6; 30 %), respectively. The majority of regimens combine new targeted agents with either chemotherapy (n = 164, 58.6 %) or endocrine therapy (n = 113, 40.4 %); a total of 8 trials (2.8 %) investigated peptide-drug conjugates. The most frequently utilized end-points were pathological complete response in the neo-adjuvant setting (n = 36, 52.9 %) and time-to-event end-points in the adjuvant and advanced settings (77.3 and 72.6 %, respectively). Our findings suggest a need for more target-matched agent development, maintenance of a value-based focus in research and a need for the clinical development of agents to treat TN/BRCA-positive and HR-positive BC.
authors.affiliation: Sunnybrook Health Sciences Centre, 2075 Bayview Ave., Room T2 023, Toronto, ON M4N 3M5 Canada.
authors.forename: Sofia
authors.initials: S
authors.lastname: Torres
authors.affiliation: British Columbia Cancer Agency, 600 West 10th Avenue, Vancouver, BC V5Z 4E6 Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: Simmons
authors.affiliation: Jewish General Hospital Segal Cancer Centre, 3755 Côte-Ste-Catherine Road, Montreal, QC Canada.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Boileau
authors.affiliation: Kaleidoscope Strategic, 146 Marion Street, Toronto, ON M6R 1E7 Canada.
authors.forename: Deanna
authors.initials: D
authors.lastname: McLeod
authors.affiliation: Kaleidoscope Strategic, 146 Marion Street, Toronto, ON M6R 1E7 Canada.
authors.forename: Ilidio
authors.initials: I
authors.lastname: Martins
authors.affiliation: Sunnybrook Health Sciences Centre, 2075 Bayview Ave., Room T2 023, Toronto, ON M4N 3M5 Canada.
authors.forename: Maureen
authors.initials: M
authors.lastname: Trudeau
keywords: Biomarkers; Breast cancer; Clinical trials; Patient profiling; Randomized trials; Target-directed research