Explaining the exceptions
A Boston team has identified activating mutations in mammalian target of rapamycin that explain a surprising 14-month complete response seen in 1 patient with bladder cancer receiving Afinitor and Votrient in a Phase I trial.1 The findings are the latest in a string of studies characterizing 'exceptional responders'. This year the National Cancer Institute plans to launch an initiative to sequence 100 such patients to help identify additional mutations that could prospectively predict drug response.
According to the NCI, up to 10% of patients in Phase II clinical trials of new drugs respond well to therapeutics that ultimately are not approved for the indication. Although a precise molecular explanation for the response in these patients often is a mystery, a series of high-profile publications have shown how next-generation sequencing can provide answers...