Liquid Biopsy Identifies Patients More Likely to Benefit From Immunotherapy in NSCLC

A blood-based test to assess tumor mutational burden (TMB) was recently discovered as being able to accurately identify patients with non—small cell lung cancer (NSCLC) who could benefit from checkpoint inhibitor treatment. The study, conducted by researchers at UC Davis, Genentech, and Foundation Medicine, was published in Nature Medicine.

Checkpoint inhibitors have been found to be more effective in patients who exhibit certain biomarkers, such as the PD-L1 protein. More recently, it was recognized that patients who have a higher TMB, or number of mutations found in specific genomic sequences in tumor cells, often are better immunotherapy candidates.

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“We wanted to know if we could transfer this TMB assay from tissue to blood,” David Gandara, MD, director of the Thoracic Oncology Program at the UC Davis Comprehensive Cancer Center, said in a statement. “We succeeded, establishing a TMB level in blood that correlates well with similar levels in tissue and was associated with favorable patient outcomes.”

Initial laboratory research methods to identify these biomarkers, such as exome sequencing, are time consuming and not always scalable for clinical care. Additionally, as many as 30% of patients with NSCLC have too little tumor tissue to facilitate these tests. The ability to use a blood test to identify relevant biomarkers is a much less invasive alternative than the traditional tissue testing.

Researchers analyzed more than 1000 blood samples from patients with advanced NSCLC and had received 2 or more lines of treatments in 2 studies, OAK and POPLAR. This retrospective study compared blood samples with tumor tissue and found that there was a strong correlation between them. The blood test was able to consistently predict which patients would benefit—with improved response and progression-free survival—from the PD-L1 inhibitor atezolizumab (Tecentriq).

Foundation Medicine is now requesting FDA approval to incorporate it into their FoundationACT (FACT) liquid biopsy. In addition, interim data from the prospective BFIRST study, presented at ASCO in June, confirmed that blood samples are a viable way to test TMB.

The authors noted that additional work is needed to better understand the dynamics and biology of blood testing for TMB, and the potential application to other indications beyond NSCLC. The blood TMB assay and the associated FACT test have already received Breakthrough Therapy Designation from the FDA.

Reference

Gandara D, Paul S, Kowanetz M, et al. Blood-based tumor mutational burden as a predictor of clinical benefit in non-small cell lung cancer patients treated with atezolizumab. [published online August 6, 2018]. Nature Med. doi.org/10.1038/s41591-018-0134-3.