The National Cancer Institute (NCI) Exceptional Responders Initiative pilot study, which started in August 2014, successfully analyzed tumor specimens from more than 100 cases, deeming the effort feasible. The pilot study results were recently reported in the Journal of the National Cancer Institute.1

“Just the ability to gather such a large number of rare and valuable tumor samples with clinical data is remarkable,” the authors of a corresponding editorial wrote.2

An exceptional response was defined in the pilot study as an unusually long response, or a partial response lasting more than 6 months or complete response to a systemic treatment for a population in which less than 10% of patients achieve a response.

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Between August 2014 to July 2017, a total of 520 cases were proposed by clinicians who were primarily from the NCI trial sites as possible exceptional responders, and 222 cases met the criteria as exceptional responders.

Cases had a median age of 59 years (range, 22-89 years), and most were alive when cases were proposed for review, with 93.2% able to provide written informed consent.

Combination chemotherapy was the most common treatment regimen received (68.4%), and 29% of cases received 1 or more antiangiogenesis agents, with or without additional chemotherapy; 6 cases received an immune checkpoint inhibitor.

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Among accepted cases, 109 cases had their tumor specimens successfully evaluated, and 6 cases had tumors with potentially clinically actionable germline mutations.

The potentially actionable mutations included pathogenic BRCA1 or BRCA2 mutations in 2 breast cancer patients, 1 non-small cell lung cancer patient, and 1 rectal cancer patient; pathogenic BRCA1 germline mutation in 1 breast cancer patient, a likely germline mutation in CHEK2 in 1 breast cancer patient, and a PALB2 mutation in 1 patient with a poorly differentiated lung cancer and a history of breast cancer.

“This study met its main feasibility goal to identify at least 100 analyzable ER [exceptional responder] cases in less than 3 years,” the study authors wrote.


  1. Conley BA, Staudt L, Takebe N, et al. The Exceptional Responders Initiative: Feasibility of a National Cancer Institute pilot study [published online April 27, 2020]. J Natl Cancer Inst. doi: 10.1093/jnci/djaa061
  2. Ford JM, Mitchell BS. One step further toward defining the exceptional cancer responder [published online April 27, 2020]. J Natl Cancer Inst. doi: 10.1093/jnci/djaa062