Researchers at UC Davis, Genentech and Foundation Medicine are the first to show that a blood-based test to assess tumor mutational burden (TMB) accurately identifies non-small cell lung cancer (NSCLC) patients who could benefit from immunotherapies called checkpoint inhibitors. The blood test offers a much less invasive and more repeatable alternative to tissue testing. The study was published online today in Nature Medicine.
“We wanted to know if we could transfer this TMB assay from tissue to blood,” said David Gandara, who directs the Thoracic Oncology Program at the UC Davis Comprehensive Cancer Center and is first author on the paper. “We succeeded, establishing a TMB level in blood that correlates well with similar levels in tissue and was associated with favorable patient outcomes.”
Checkpoint inhibitors take the molecular brakes off T cells, allowing them to attack tumors. However, they work best in patients who exhibit certain tumor biomarkers. One of these is the PD-L1 protein. More recent is tumor mutational burden – the number of mutations found in specific genomic sequences in tumor cells of an individual patient. Patients with higher TMB are often better candidates for immunotherapy.
Translating these findings into clinical practice is now feasible. The initial laboratory research methods used to identify these biomarkers, such as exome sequencing, take a long time and are not always scalable for clinical care. In addition, as many as 30 percent of NSCLC patients have too little tumor tissue to facilitate these tests. A fast, minimally invasive blood test would be the ideal solution.
“There are patients for whom the biopsy is inadequate from the start, or the tissue is used for routine pathology and we don’t have enough tissue left to do either genomic testing or tissue TMB,” Gandara said. “If we can do it in blood in one test, that offers many advantages for patients who have had an inadequate biopsy.”
In addition, because it’s much less invasive, a blood test could be repeated to determine if a treatment is effective or provide an additional option for patients who might not tolerate a traditional biopsy in the first place.
Blood tests, or liquid biopsies as they are sometimes called, are finding more and more success in the lung cancer arena. From being able to detect early stage lung cancer to improving lung cancer risk assessments in smokers, minimally invasive blood tests are becoming increasingly useful tools for lung cancer researchers.