Clinical outcomes in non-small-cell lung cancer patients treated with EGFR-tyrosine kinase inhibitors and other targeted therapies based on tumor versus plasma genomic profiling

Hai T. Tran, Vincent K. Lam, Yasir Y. Elamin, Lingzhi Hong, Rivka Colen, Nabil A. Elshafeey, Islam S.A. Hassan, Mehmet Altan, George R. Blumenschein, Waree Rinsurongkawong, Melvin J. Rivera, Mayra E. Vasquez, Brett W. Carter, Lauren E. Byers, Anne S. Tsao, Don L. Gibbons, Frank Fossella, Bonnie S. Glisson, Jianjun Zhang, John V. Heymach

Research output: Contribution to journalReview articlepeer-review

Abstract

PURPOSE To compare clinical outcomes in a cohort of patients with advanced non-small-cell lung cancer (NSCLC) with targetable genomic alterations detected using plasma-based circulating tumor DNA (ctDNA) or tumor-based next-generation sequencing (NGS) assays treated with US Food and Drug Administration-approved therapies at a large academic research cancer center. METHODS A retrospective review from our MD Anderson GEMINI database identified 2,224 blood samples sent for ctDNA NGS testing from 1971 consecutive patients with a diagnosis of advanced NSCLC. Clinical, treatment, and outcome information were collected, reviewed, and analyzed. RESULTS Overall, 27% of the ctDNA tests identified at least one targetable mutation and 73% of targetable mutations were EGFR-sensitizing mutations. Among patients treated with first-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapies, there were no significant differences in progression-free survival of 379 days and 352 days (P value =.41) with treatment based on tissue (n = 40) or ctDNA (n = 40), respectively. Additionally, there were no differences in progression-free survival or objective response rate among those with low (n = 8, 0.01%-0.99%) versus high (n = 16, ≥ 1%) levels of ctDNA of the targetable mutation as measured by variant allele frequency (VAF). Overall, there was excellent testing concordance (n = 217 tests) of. 97%, sensitivity of 91.7%, and specificity of 99.7% between blood-based ctDNA NGS and tissue-based NGS assays. CONCLUSION There were no significant differences in clinical outcomes among patients treated with approved EGFR-TKIs whose mutations were identified using either tumor- or plasma-based comprehensive profiling and those with very low VAF as compared with high VAF, supporting the use of plasma-based profiling to guide initial TKI use in patients with metastatic EGFR-mutant NSCLC.

Original languageEnglish (US)
Pages (from-to)1241-1249
Number of pages9
JournalJCO Precision Oncology
Volume5
DOIs
StatePublished - 2021
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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