CLINICAL EVIDENCE

Assessment of EGFR mutations in matched urine, plasma and tumor tissue in NSCLC patients treated with rociletinib (CO-1686)

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Assessment of EGFR mutations in matched urine, plasma and tumor tissue in NSCLC patients treated with rociletinib (CO-1686)

Introduction

  • Approximately 60% of patients who receive an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor develop the acquired resistance mutation T790M.1
  • Acquisition of suitable tumor tissue is a challenge for a considerable fraction of advanced non-small cell lung cancer (NSCLC) patients who require EGFR testing.
  • We examined the detection of EGFR T790M mutation in circulating tumor DNA (ctDNA) from urine, assessed urine sample requirements, and compared the results with contemporaneously matched tumor tissue and plasma in TIGER-X, a phase 1/2 clinical study of rociletinib in previously treated patients with advanced NSCLC and mutant EGFR.

Methods

Patients

  • Pretreatment urine or plasma was obtained from 68 patients with available tumor biopsy result in TIGER-X. Matched urine or plasma was available for 51 of these patients. Urine was available for 63 of these patients.
  • Patients enrolled in TIGER-X were required to have documented evidence of an EGFR-activating mutation in their medical record.

T790M analysis

  • Tissue: therascreen® EGFR RGQ polymerase chain reaction (PCR) test.
  • Urine and plasma: Trovagene quantitative PCR next-generation sequencing (NGS) EGFR T790M assay.

Highlighted Tables and Graphs

Urine/Tissue Concordance for T790M Testing (urine 90-100mL)

Urine/Plasma Concordance for T790M Testing (urine 90-100mL)

Sensitivity of T790M in M1a vs M1b Disease

Conclusions

  • The analysis of ctDNA from urine identified a similar proportion of T790M- positive patients as tissue- or plasma-based testing, with the highest PPA among patients with approximately half of a normal void (90–100 mL, PPA=93%).
  • Urine and tissue tests complement one another; each test identifies cases missed by the other. Discordant samples between urine and tissue that were not identified by the tumor test may be explained by tumor heterogeneity and/or inadequate biopsy.
  • EGFR mutation detection from urine should be considered a viable approach, particularly when tumor tissue is not available.
  • Monitoring urine ctDNA T790M mutation levels longitudinally is feasible and is being further explored as a means to inform choice of therapy.
Trovera

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