We recommend that all patients with advanced nonsquamous NSCLC get a broad next-generation sequencing panel. Updated guidelines from the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology have also recommended that patients get tested with a broad panel. We recommend that you test broadly early in the disease course because of the challenges of retesting and the rapid rate of the development of new effective targeted therapies. As a person who has worked with sequencing NSCLC for approximately 16 years, I have found that it is challenging to go back and retest a patient’s tumor when there is a new target for which there is a new effective treatment. We have found that you cannot always retrieve the specimen and perform additional testing for a variety of reasons (eg, the specimen may be exhausted). Therefore, you want to make sure that the testing is done up front if at all possible.

It is also helpful to have a broad panel for all solid tumors so that you do not have to perform different tests for different malignancies. For instance, a number of mutations occur across tumors. BRAF V600E mutations occur in melanoma, colon cancer, and lung cancer. Overall, we are seeing approximately 1 to 2 new FDA-approved indications for a different oncogenic driver every year or so, and we now have approved indications for drugs against EGFR, ALK, ROS1, NTRK, and RET rearrangements, BRAF V600E, and MET exon 14 skip mutations. There will be ongoing efforts to find a treatment for targets that are present in as low as 1% or more of patients with NSCLC, so we expect that there will be an increased number of FDA-approved indications in the future.

Plasma testing of biomarkers is mostly limited to the research setting at the current time, with a few exceptions. One exception is the assessment of acquired resistance to first-generation tyrosine kinase inhibitors due to T790 M mutations. For these mutations, either a biopsy or a plasma test may be appropriate. The problem with plasma testing, however, is that you need to have a relatively heavy tumor burden to have enough DNA shedding to carry out accurate testing. Another exception is a case involving a patient who does not have a tumor that is accessible for biopsy (ie, a brain metastasis).