Novel Clinical Trial Designs In Oncology: An Histology-Independent Approach

For years, drug developers have used histology as the fundamental analytical unit by which they study new agents for their effectiveness. Homogenous patient cohorts (based on their histological distinctions) produce more predictable outcomes. This rationalization is consistent with the mechanisms of action for many cytotoxic agents and some classes of targeted therapies. For example, the cytotoxic effects of taxanes in breast, ovarian, prostate, and lung tissues are likely attributable to inherent metabolic properties of the tumor, such as drug absorption/uptake, DNA replication/cell division, and mechanisms of drug resistance. Likewise, the effects of angiogenesis inhibitors (e.g., bevacizumab) in certain solid tumors are related to the neovascularization properties of specific tumors and the molecular targets that are involved.

Despite the technical merits – and proven success – of this path for drug development, histology-based approaches can be inefficient...