National Cancer Institute investigating trial outliers to resurrect 'failed' drugs

Last year the National Cancer Institute announced the launch of an initiative meant to examine failed clinical trials in search of "exceptional responders": patients who responded well to drugs that the bulk of the trial population didn't.

Now, after sifting through 10 years' worth of clinical trials, NCI's Cancer Diagnosis Program has identified about 100 of these unique patients so far, according to Bloomberg.

Memorial Sloan-Kettering Cancer Center in New York, Dana-Farber Cancer Institute and Massachusetts General Hospital in Boston and the Broad Institute in Cambridge, MA, have teamed up with NCI to look for these outlier patients and eventually establish a national database of patient data for researchers.

The NCI defines exceptional responders as cancer patients who had a complete response or partial response to treatment for at least 6 months in a clinical trial in which less than 10% of patients responded.

One such patient was the subject of a study published in March in Cancer Discovery. The patient, who had advanced bladder cancer, experienced a complete response for 14 months to the drug combination everolimus (Afinitor) and pazopanib (Votrient) in a Phase I trial. In the trial, investigators recruited 9 patients with advanced solid tumors, including 5 with bladder cancer, whose diseases had progressed despite treatment with standard therapies. Patients received one to 13 cycles of everolimus and pazopanib.

One of 5 of the bladder cancer patients had a complete response to the treatment, and genomic profiling of his tumor revealed two unique sequences that may have caused this exceptional response. Investigators identified a mutation in a gene called TSC1 that may have led to the result. The same gene mutation was found in several other patients in the clinical trial, including two who had minor responses to everolimus. The findings indicate that everolimus may be used to treat bladder cancer in patients with these specific gene mutations.

Exceptional responders such as these may provide the impetus to resurrect other so-called failed drugs for use in certain patients. But first, scientists need to understand the genetic mechanisms at work in outlying cases. Then, investigators can work toward finding hypertargeted anticancer therapies that could improve patient selection for certain treatments as well as boost patient response to therapy and advance new treatment regimens.

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