title: Evaluating the Utility of a 'N-of-1' Precision Cancer Medicine Strategy: The Case for 'Time-to-Subsequent-Disease Progression'.
abstract: It is increasingly recognized that cancer is a highly heterogeneous group of illnesses even within a particular organ site (e.g., breast, lung, colon, etc.). This observation presents a serious challenge to the traditional concept of phase 3 randomized trials designed to define therapeutic efficacy of a novel treatment strategy. For while 10% of the patients with a common malignancy (e.g., non-small-cell lung cancer) may be sufficient to consider such an effort, enrolling a sufficient number of patients into a clinical trial in a timely manner to define clinical utility would be extremely difficult if the population in question represented only 1% of this population, and essentially impossible if one wished to explore the benefits of treatment in a rarer neoplasm (e.g. ovarian cancer). Therefore, in the new era of precision cancer medicine, alternative research designs are imperative. One option would be to compare the time-to-disease progression of an individual cancer patient following treatment with a novel therapeutic to the time-to-disease progression for that specific patient on her/his immediately preceding treatment. The rationale for this strategy and early experience with this innovative approach to evaluating the efficacy of anticancer therapy is highlighted in this report.
authors.affiliation: Cancer Treatment Center of America in Philadelphia, Pa., USA.
authors.forename: Maurie
authors.initials: M
authors.lastname: Markman
authors.forename: Kim
authors.initials: K
authors.lastname: Kramer
authors.forename: Ricardo H
authors.initials: RH
authors.lastname: Alvarez
authors.forename: Glen J
authors.initials: GJ
authors.lastname: Weiss
authors.forename: Eugene
authors.initials: E
authors.lastname: Ahn
authors.forename: George William
authors.initials: GW
authors.lastname: Daneker
mesh_terms: D017326:Clinical Trials, Phase III as Topic; D018450:Disease Progression; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D057285:Precision Medicine; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D013997:Time Factors