27IN - The importance of patient selection in treatment efficacy

Date 01 October 2012
Event ESMO Congress 2012
Session A paradigm shift in early drug development: Individualizing to more patient benefit
Topics Clinical research
Personalised/Precision Medicine
Basic Scientific Principles
Basic Principles in the Management and Treatment (of cancer)
Presenter Steinar Aamdal
Authors S. Aamdal
  • Dept. Of Clinical Cancer Research, Oslo University Hospital, 0310 - Oslo/NO


The importance of patient selection in treatment efficacy Cohorts of patients selected according to biomarkers are shifting the cancer treatment paradigm from population based to personalized medicine introducing a new area termed theragnostics in which the combination of diagnostics and therapeutics identifies patients most likely to benefit or not from a treatment regimen. Apart from safety and toxicity assessment phase I trials now also test hypothesis, determine target engagement, biologic response, identify the appropriate patient population, proof-of-concept, and identify potential predictive biomarkers in Phase II and Phase III trials. There are several strategies to select patients on molecular bases for early drug development. 1) The molecular alterations are sufficient frequent in a tumor type that without pre-selection retrospective analysis of the mutation can be carried out. A retrospective analysis on fixed tissue can confirm the drug activity in presence of the molecular alteration. Selection is then based on tumor type, not on molecular analysis. Such selection would put a number of patients at risk of exposure to a study drug despite not presenting the target of interest. 2) Prescreening patients by sending tumor tissue to a central laboratory for analysis just before inclusion in a trial. This ensures state-of the art central laboratory analyses. Amount of tumor tissue may become an issue if several labs are involved. Turnaround time between molecular analyses and trial initiation may become too lengthy for patients with advanced disease. 3) Local prescreening of patients while still on standard treatment. Less tumor material is needed and no delay from progression on standard therapy to recruitment in a clinical trial. Multiple patient consent forms are not necessary. However patients will be screened for participating, but never will enter trial due to early disease progression. Intra-tumor heterogeneity, presence of more than one clone in the tumor and inter-tumor heterogeneity, the presence of different genetic alterations in different metastases from a single patient is a major challenge to patient selection. Single cor biopsy may lead to underestimation of the mutations in the tumor and could influence the efficacy of molecular targeted therapies even in carefully selected patients.


The author has declared no conflicts of interest.