Plasma ctDNA Analysis for Detection of the EGFR T790M Mutation in Patients with Advanced non-small Cell Lung Cancer.

INTRODUCTION:

Tumor biopsies for detecting epidermal growth factor receptor mutations (EGFRm) in advanced non-small cell lung cancer (NSCLC) are invasive, costly and not always feasible for patients with late-stage disease. The clinical utility of the cobas® EGFR Mutation Test v2 with plasma samples from patients with NSCLC at disease progression following previous EGFR-tyrosine kinase inhibitor (TKI) therapy was investigated to determine osimertinib treatment eligibility.

METHODS:

Matched tumor tissue and plasma samples from patients screened for AURA extension and AURA2 phase II studies were tested for EGFRm using tissue- and plasma-based cobas® EGFR Mutation Tests v2. Plasma test performance was assessed using the cobas tissue test and a Next Generation Sequencing (NGS) method (MiSeq, Illumina Inc.) as references. Objective response rate (ORR), measured by blinded independent central review, was assessed in patients receiving osimertinib with a plasma T790M mutation positive status.

RESULTS:

During screening 551 patients provided matched tumor tissue and plasma samples. Pooled analysis of positive and negative percent agreements (PPA and NPA) between cobas plasma and tissue tests for T790M mutation detection were 61% and 79%, respectively. Comparing cobas plasma test with NGS demonstrated PPA and NPA ≥90%. ORR was 64% (95% CI: 57-70) in T790M mutation positive patients by both cobas tissue and plasma tests (evaluable-for-response).

CONCLUSION:

The cobas plasma test detected the T790M mutation in 61% of tumor tissue T790M mutation positive patients. To mitigate the risk of false negative plasma results, patients with a negative plasma result should undergo a tissue test where feasible.

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