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Plasma vs Tissue Genotyping and Outcomes With Osimertinib in Advanced Non–Small Cell Lung Cancer

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Key Points

  • Sensitivity of plasma genotyping for the T790M resistance mutation was 70%, and T790M was detected in plasma in 31% of patients with T790M-negative tumors.
  • Response rates and progression-free survival were nearly identical in plasma and tissue T790M–positive patients.

Patients with advanced non–small cell lung cancer (NSCLC) positive for the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor T790M resistance mutation on a plasma assay had similar outcomes with the EGFR tyrosine kinase inhibitor osimertinib (Tagrisso) as did those who were positive on tissue genotyping, according to a study reported by Oxnard et al in the Journal of Clinical Oncology. The findings suggest that a validated plasma assay may allow some patients to avoid tumor biopsy for detection of the mutation.

Study Details

Osimertinib is a third-generation EGFR tyrosine kinase inhibitor, agents that have been found to be active against tumors with the T790M resistance mutation against conventional EGFR tyrosine kinase inhibitors. In the current study, findings with genotyping of cell-free plasma DNA were compared with those using tumor genotyping from a central laboratory in 216 patients from phase I and expansion cohorts in a previous trial of osimertinib. Outcomes of osimertinib treatment were assessed according to plasma assay T790M-positive or -negative status.

Findings With Plasma Assay

The sensitivity of plasma genotyping for detecting the T790M resistance mutation was 70%. Of 58 patients with T790M-negative tumors, the mutation was detected in plasma in 18 of them (31%). Objective response rates (63% and 62%) and median progression-free survival (9.7 and 9.7 months) were similar in patients with T790M-positive plasma and those with T790M-positive tumors.

Patients with T790M-negative plasma had favorable outcomes (response rate = 46%, median progression-free survival = 8.2 months). However, tumor genotyping distinguished subsets of patients positive for T790M with better outcome (response rate = 69%, median progression-free survival =16.5 months) and patients negative for T790M with poorer outcomes (response rate = 25%, median progression-free survival = 2.8 months).

The investigators concluded: “In this retrospective analysis, patients positive for T790M in plasma have outcomes with osimertinib that are equivalent to patients positive by a tissue-based assay. This study suggests that, upon availability of validated plasma T790M assays, some patients could avoid a tumor biopsy for T790M genotyping. As a result of the 30% false-negative rate of plasma genotyping, those with T790M-negative plasma results still need a tumor biopsy to determine [the] presence or absence of T790M.”

The study was supported by the National Cancer Institute, Stading Younger Cancer Research Foundation, Harold and Gail Kirstein Lung Cancer Research Fund, Phi Beta Psi Charity Trust of the National Institutes of Health, and AstraZeneca.

Geoffrey R. Oxnard, MD, of Dana-Farber Cancer Institute, is the corresponding author of the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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