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.
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.
- 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.