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

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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 Geoffrey R. Oxnard, MD, of Dana-Farber Cancer Institute, and colleagues in the Journal of Clinical Oncology. The findings suggest a validated plasma assay may allow some patients to avoid tumor biopsy for detection of the mutation.

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.”

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. ■

Oxnard GR, et al: J Clin Oncol. June 27, 2016 (early release online).




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