"The emerging view of cancer is an increasingly diverse set of rare diseases with overlapping etiology and molecular drivers (1). The evolving definition of personalized oncology centers on the development and vetting of many specific, targeted, low-toxicity molecular scalpels that can be used individually or in combinations to tailor a patient’s cancer treatment. The bottleneck of drug development is the testing phase, and there are numerous barriers to novel chemotherapeutic introduction to the clinic.
The I-SPY2 trial has received a lot of press lately, and rightfully so: it’s a bayesian study designed to adaptively match patient genotypes of appropriate therapies in a rotating 5-arm clinical trial that can quickly take on a new agent once one of the test arms graduates, ready for Phase III trials that (theoretically) have a might higher chance for success, with fewer patients (2, 3). The trial has been engineered to make cancer drug trials quicker and less expensive, and more information can be found here.
The I-SPY2 trial is co-directed by Laura Esserman, who gave an illuminating talk at the UCSD Moores Cancer Center last week. Most targeted therapies are tested in clinical trials in heavily pre-treated patients in the metastatic setting, and often without molecular biomarkers. Agents tested in the metastatic setting often see a 2-4 year knowledge turn, while those in the adjuvant setting often come with a 6-9 year knowledge turn. This is simply too slow (and uses too many patients and is too expensive) to realize the vision of personalized oncology.