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Novel Molecular Markers at Forefront of NSCLC Research

Kristi Rosa
Published: Wednesday, Nov 28, 2018

Ardaman Shergill, MD

Ardaman Shergill, MD

Tumor mutational burden (TMB), NTRK, and RET are all molecular markers at the forefront of current research in non–small cell lung cancer (NSCLC), and investigators are in the early phases of learning how they can be used to clinically to benefit patients, said Ardaman Shergill, MD.

fusions, in the NSCLC paradigm.

OncLive: Could you highlight the research exploring TMB as a biomarker for NSCLC?

Shergill: For TMB, I discussed 2 trials—although there are a lot more data available. One of the 2 trials that I talked about was CheckMate-227, which was a very complex trial designed to test nivolumab plus ipilimumab or nivolumab compared with chemotherapy based on PD-L1 expression. One of the co-primary endpoints of the trial was to look at TMB.

They further looked at patients who had low PD-L1 expression and high TMB, and those patients also responded to immunotherapy. Therefore, in essence, this helped to select a group of patients who could respond to immunotherapy even when their PD-L1 status—which is a currently used biomarker—is not high.

What trials are looking at RET fusions as an emerging biomarker for NSCLC?

With RET, there were 2 drugs that I talked about in my presentation that were tested in rapid phase I studies. For these studies, there were only 1 or 2 patients enrolled, and the doses were rapidly escalated to treat those patients. Investigators showed significant intracranial and extracranial responses for a patient who progressed on multiple lines of therapy, and that was quite significant in that field. This was a patient who progressed through chemotherapy, immunotherapy, and targeted therapy, and then responded to the RET inhibitor, LOXO-292[KR1], at that time.

What is the prevalence of RET abnormalities?

It depends on the institution or where the person is being treated and how they perform molecular testing for patients. At most places, testing for mutations such as EGFR and ALK are becoming standard. Therefore, we test these mutations, but not everybody is getting comprehensive panel testing for the mutations the tumors might have.
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