Adding next-generation sequencing (NGS), using plasma samples, to the routine management of metastatic non-small cell lung cancer (NSCLC) has the potential to improve the delivery of targeted therapy by increasing the detection of targetable mutations, according to a recent study.1

The study included 323 patients with metastatic NSCLC who were undergoing plasma testing as part of routine management of their disease. Plasma NGS was done using a 73-gene commercial platform. Of the 323 patients, 229 had concurrent plasma and tissue NGS or were unable to complete tissue testing.

Use of tissue testing only found targetable mutations for 20.5% of patients. In contrast, adding plasma NGS increased the rate of targetable mutation discovery to 35.8% of patients. The researchers noted that 33% of patients with a therapeutically targetable mutation detected in plasma were able to avoid invasive biopsy. 

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Overall, 67 patients received a targeted therapy based on the results from NGS testing. Some identified targets included EGFR, ALK, BRAF, BRCA1, and MET.  Of 42 patients with evaluable treatment results, 85.7% achieved either complete response, partial response, or stable disease.

In an editorial that accompanied the study, Bishal Gyawali, MD, PhD, of Brigham and Women’s Hospital, Boston, Massachusetts; and Howard West, MD, of the Swedish Cancer Institute, Seattle, Washington, concluded that these results do not yet show that plasma NGS can replace tissue testing, as about one-third of patients with a targetable mutation who had tissue and plasma NGS testing had a mutation found only in the tissue. However, they added that “the study compellingly demonstrates that plasma NGS can obviate the need for tissue NGS in patients in whom plasma testing demonstrates a mutation, given the response and disease control rate among patients who had therapeutically targetable mutations identified from plasma.”


  1. Aggarwal C, Thompson JC, Black TA, et al. Clinical implications of plasma-based genotyping with the delivery of personalized therapy in metastatic non-small cell lung cancer [published online October 11, 2018]. JAMA Oncol. doi: 10.1001/jamaoncol.2018.4305
  2. Gyawali B, West H. Plasma vs tissue next-generation sequencing in non-small cell lung cancer — either, both, or neither? [published online October 11, 2018]. JAMA Oncol. doi: 10.1001/jamaoncol.2018.4304