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Six fast facts about exceptional responders
They are, unfortunately, a rarity — the so-called “exceptional responders” who are particularly sensitive to certain cancer treatments when most others fail to respond at all. According to the National Cancer Institute, an “exceptional responder” is a patient who has a complete or partial response that lasts at least 6 months post-treatment, in a clinical trial in which fewer than 10% of patients responded.
Because they are exceptional, and because they do exceptionally well, oncologists are eager to better understand these patients. And while genomic sequencing appears to be yielding some answers, the implementation of this approach is not yet cost-effective.
For the January issue, HemOnc Today spoke with experts on the topic of exceptional responders to find out more about these remarkable patients. Click here to read the full story.
Based on these interviews and current literature, here is what you need to know.
1. More than 100 exceptional responders have been identified, and a database study is being designed to better understand them.
The National Cancer Institute (NCI) has undertaken a pilot study to formulate a database of medications and genetic mutations linked to exceptional or “outlier” responses. After reviewing all NCI-supported early clinical trials from the past decade, researchers have pinpointed more than 100 patients who meet the “exceptional responder” criteria.
2. In bladder cancer, exceptional responders to everolimus may have mutations of TSC1.
In a recent trial of everolimus (Afinitor, Novartis) in patients with metastatic urothelial cancer, one remarkable finding stood out from the otherwise negative findings. Although only two of the 45 patients achieved a response by RECIST criteria, one of the two, a 75-year-old woman, achieved a 4-year remission. After sequencing the patient’s genome, researchers found that she had a somatic mutation in TSC1, which appears to be linked with everolimus sensitivity.
3. Genomic analysis of exceptional responders could be exceptionally expensive.
Although it has become clear to researchers that genomic study of exceptional responders is crucial, this comes at a hefty price tag. Because determining genetic mutations behind exceptional responses may require sequencing the entire genome and RNA, the cost can exceed $20,000 per patient. Researchers are trying to focus their studies in order to keep this cost as low as possible.
4. The PROFILE study aims to make every patient an exceptional responder.
Usually, investigations into exceptional patient responses focus on the small number of patients who achieved the exceptional response to a treatment. Clinicians then seek to match the treatment with other patients that have the same mutations.
However, an approach introduced by Dana-Farber Cancer Institute and Brigham and Women’s Hospital genetically screens all cancer patients prior to beginning treatment. By identifying the genetic mutations involved in each patient’s tumor, the physicians can choose treatments tailored specifically to these genetic factors.
5. Exceptional resistance also provides key information.
On the other side of the coin from exceptional responders are those who respond particularly poorly to treatment. Researchers have recently begun assessing patients with acute myeloid leukemia, and comparing long first-remission patients with those who were therapy-resistant. It is likely that poor responders will also warrant genomic testing.
6. The ‘basket’ approach to clinical trials will focus on mutation type rather than tumor type.
Some institutions have begun to adapt their clinical trials in order to better understand the genomic traits of exceptional responders. These “basket” studies focus on mutation type rather than tumor type.