Clinical Application of Genomic Profiling With Circulating Tumor DNA for Management of Advanced Non-Small-cell Lung Cancer in Asia

Clin Lung Cancer. 2018 Sep;19(5):e601-e608. doi: 10.1016/j.cllc.2018.04.022. Epub 2018 May 7.

Abstract

Background: Genomic profiling of cell-free circulating tumor DNA (ctDNA) is a potential alternative to repeat invasive biopsy in patients with advanced cancer. We report the first real-world cohort of comprehensive genomic assessments of patients with non-small-cell lung cancer (NSCLC) in a Chinese population.

Patients and methods: We performed a retrospective analysis of patients with advanced or metastatic NSCLC whose physician requested ctDNA-based genomic profiling using the Guardant360 platform from January 2016 to June 2017. Guardant360 includes all 4 major types of genomic alterations (point mutations, insertion-deletion alterations, fusions, and amplifications) in 73 genes.

Results: Genomic profiling was performed in 76 patients from Hong Kong during the 18-month study period (median age, 59.5 years; 41 men and 35 women). The histologic types included adenocarcinoma (n = 10), NSCLC, not otherwise specified (n = 58), and squamous cell carcinoma (n = 8). In the adenocarcinoma and NSCLC, not otherwise specified, combined group, 62 of the 68 patients (91%) had variants identified (range, 1-12; median, 3), of whom, 26 (42%) had ≥ 1 of the 7 National Comprehensive Cancer Network-recommended lung adenocarcinoma genomic targets. Concurrent detection of driver and resistance mutations were identified in 6 of 13 patients with EGFR driver mutations and in 3 of 5 patients with EML4-ALK fusions. All 8 patients with squamous cell carcinoma had multiple variants identified (range, 1-20; median, 6), including FGFR1 amplification and ERBB2 (HER2) amplification. PIK3CA amplification occurred in combination with either FGFR1 or ERBB2 (HER2) amplification or alone.

Conclusion: Genomic profiling using ctDNA analysis detected alterations in most patients with advanced-stage NSCLC, with targetable aberrations and resistance mechanisms identified. This approach has demonstrated its feasibility in Asia.

Keywords: ALK; EGFR; Liquid biopsy; NSCLC; Targetable alterations.

MeSH terms

  • Adenocarcinoma / blood
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / secondary
  • Adenocarcinoma / therapy
  • Adult
  • Aged
  • Aged, 80 and over
  • Asia
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Non-Small-Cell Lung / blood
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Carcinoma, Squamous Cell / blood
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / secondary
  • Carcinoma, Squamous Cell / therapy
  • Circulating Tumor DNA / genetics*
  • Cohort Studies
  • Disease Management
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling*
  • Genomics
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Lung Neoplasms / blood
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Prognosis

Substances

  • Biomarkers, Tumor
  • Circulating Tumor DNA