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The Exceptional Responders Initiative: Welcoming More Cases

, by NCI Staff

As part of its Exceptional Responders Initiative, NCI continues to reach out to the oncology community.

The initiative is collecting cases in which patients with any cancer had dramatic and long-lasting responses to standard and experimental treatments that were not seen in similar patients who received the same treatment.

By studying tissue, clinical, and genomic data from these patients, NCI scientists hope to learn whether such exceptional responses can provide broader insights into the genetic mechanisms that underlie such responses and suggest  therapeutic options that weren’t previously apparent, explained Barbara Conley, M.D., of NCI’s Division of Cancer Treatment and Diagnosis.

Since its launch in September 2014, more than 70 cases have been provisionally accepted, with additional patient cases coming to NCI for review. Provisionally accepted cases have passed initial NCI review, although the investigators/clinicians who submitted the cases must work with NCI to complete several additional steps (e.g., IRB approval, provision of complete clinical data and tissue for the case, etc.) so that the case can officially be included in the Exceptional Responders’ study component.

“We’re pleased with the response thus far,” said Dr. Conley. “But to really achieve what we want from this initiative—to further guide the development of cancer precision medicine—we need to analyze more cases.”

The potential of studying exceptional responders was highlighted in a study published last year, which found that one patient with metastatic bladder cancer who was treated with two targeted therapies as part of a phase I clinical trial had a complete response that lasted more than a year. Whole-exome sequencing showed that the patient had two activating mutations in the mTOR gene (one of the drugs included in the trial targets the mTOR signaling protein) that had not been previously seen in human cancer.

The presence of two mutations that make mTOR signaling more active than normal within the same bladder tumor might have made it unusually responsive to the mTOR inhibitor, the research team that led the study concluded. 

Patients whose cases are eligible for the Exceptional Responders Initiative include both those being treated with targeted therapies as part of a clinical trial and those being treated with standard regimens (including targeted therapies but excluding localized treatments like surgery or radiation) outside of a trial, Dr. Conley explained.

Tumor samples from accepted cases will undergo whole-exome, RNA, and targeted deep sequencing to identify potential molecular features that may have accounted for the response. NCI will place this information in a controlled access database so that qualified investigators can access it for further research. 

Dr. Conley encourages clinical trial investigators to review data from their completed clinical trials and treating oncologists to look back in their patient records to identify potential cases of exceptional responses and submit them for consideration. Clinicians who submit cases also will become part of the analysis team for that case.

“While there is some work involved in submitting a case—and some reimbursement for it—the potential return on that effort is substantial,” she stressed. “The promise of precision medicine is real, and we feel that this initiative can play a big role in moving it forward.”

Details about case eligibility and how to submit cases are available on the NCI Website.

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