Data drives adaptations in I-Spy 2 cancer trial

A cancer drug trial volunteer apparently on the road to recovery may be strengthening the case for adaptive trial design. The seeming success of 37-year-old breast cancer sufferer Kerry Landreth in the I-Spy 2 trial, as described in the Wall Street Journal, shows the contribution that adaptive trial data can make in the efforts of drug developers.

That contribution comes in the form of Phase III trials that are smaller--perhaps 300 subjects rather than 3,000--and faster than their traditionally designed counterparts. And it's made possible by adaptive enrollment techniques that identify from earlier-stage trials the subjects most likely to respond positively to treatments.

I-Spy 2, targeting women with aggressive breast cancers that have not spread to other organs, aims to match experimental drugs with tumor types identified via biomarkers. The novel trial is testing multiple drug candidates simultaneously to help advance those that appear effective to late-stage trials.

Study co-leaders Laura Esserman of the University of California, San Francisco, and Don Berry of the M.D. Anderson Cancer Center championed the use of adaptive design in I-Spy 2. The design calls for researchers to evaluate data throughout the trial, rather than the common practice of reviewing all data at the end of the trial, and to use that data in their decision-making about which subjects get which drugs at later trial stages. They use molecular analysis to put subjects into one of 10 biomarker categories and then steer them to the one of five drugs candidates that's shown the best results with that category.

The goal is to pair drug with biomarker signatures and advance the pair into a small Phase III trial that runs without those subjects who haven't shown benefit, raising the likelihood of trial results that will lead to drug approval. What's still unclear, however, is whether any given trial will meet regulatory muster.

- here's the article