Agency hopes that clinical trial 'subgroups' of one patient may open up new biology and rescue failed anticancer drugs.

The lowdown: Even in failed oncology clinical trials, some patients may experience huge benefits from treatment. Using genomic analysis techniques that have only come online in the past few years, the US National Cancer Institute (NCI) is now going to analyse the genetics of these so-called 'exceptional responders' in the hope of identifying other patients who could also benefit. While the NCI has being planning and piloting this extreme-subgroup analysis approach for the past two years, it has now put out a formal call for academic and industry investigators to get involved.

The agency defines exceptional responders as patients who “received a treatment in which fewer than 10% of patients had a complete response or a durable (6 month) partial response” and “achieved either a complete response (CR) or a partial response (PR) with duration of at least 6 months as defined by RECIST (Response Evaluation Criteria in Solid Tumors) criteria” or other appropriate response criteria. A committee will review suspected, submitted exceptional responder case studies and, where feasible, will run DNA and RNA analyses on stored biospecimens. “The investigators may examine up to 300 cases to see if they would be able to acquire useable data on 100 cases,” says the NCI in a statement.

“We have never thought of this as anything but a feasibility and hypothesis-generating study,” Barbara Conley, Associate Director of the Cancer Diagnosis Program at the NCI, previously told Nature Reviews Drug Discovery (Nature Rev. Drug Discov. 13, 401–402; 2014). “But given that we have these genomic capabilities to look at what is different in the tumour DNA of exceptional responders, we have to see whether we can do any better at getting the right drug to the right patient.”

The programme was prompted by the discovery that an exceptional responder in an everolimus trial had mutations in TSC1 (which encodes hamartin), explaining the unusual response in an otherwise failed trial (Science 12, 221; 2012).