Patients with advanced non-small cell lung cancer (NSCLC) positive for T790M in plasma may have osimertinib-related outcomes equivalent to patients positive by a tissue-based assay, according to a study published in the Journal of Clinical Oncology.1 These findings suggest that some patients could avoid a tumor biopsy for T790M genotyping when validated plasma T790M assays become available.

Researchers collected plasma from patients who had acquired EGFR-TKI resistance and evidence of a common EGFR-sensitizing mutation in a first human study of osimertinib.

BEAMing (a digital polymerase chain reaction test) was used to perform genotyping of cell-free plasma DNA, which was assessed for plasma genotyping accuracy by using tumor genotyping from a central laboratory as reference. Objective response rate and progression-free survival were analyzed in all patients who were T790M-positive or T790M-negative.


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The researchers found a 70% sensitivity of plasma genotyping for detection of T790M. Among 58 patients with T790M-negative tumors, T790M was found to be detected in the plasma of 18.

Objective response rate and median progression-free survival were found to be similar in patients with T790M-positive plasma or T790M-positive tumor results.

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While patients with T790M-negative plasma were found to have overall favorable outcomes, tumor genotyping distinguished a subset of patients positive for T790M who had better outcomes, along with a subset of patients negative for T790M with poor outcomes.

Reference

  1. Oxnard GR, Thress KS, Alden RS, Lawrance R, Paweletz CP, Cantarini M, et al. Association between plasma genotyping and outcomes of treatment with osimertinib (AZD9291) in advanced non-small-cell lung cancer. [published online ahead of print June 27, 2016.] J Clin Oncol. doi: 10.1200/JCO.2016.66.7162.