Abstract 1373
Background
Genomic profiling of ctDNA has proven to be an effective alternative to repeat invasive biopsy in patients (pts) with advanced cancers. There is also the advantage of a more comprehensive approach over tissue-based assays with the ability to provide a summary of tumour heterogeneity.
Methods
We performed a retrospective review of Hong Kong pts with advanced/metastatic NSCLC whose physician requested ctDNA-based genomic profiling utilizing the Guardant360 platform between Jan 2016 - Jun 2017. Guardant360 includes all four major types of genomic alterations (point mutations, and selected indels, fusions, and amplifications) and completely sequences exons in 73 target genes.
Results
ctDNA testing was performed in 76 pts over this 18-month period (Median Age: 59.5 years (range 42-87), M:F 41:35). Histologies, as reported by the ordering physician, include squamous (SqCC) (n = 7), adenocarcinoma (Adeno) (n = 10), and NSCLC-not otherwise specified (NSCLC-NOS) (n = 58). In SqCC, all 7 pts had multiple detectable variants identified (range: 2-20 variants, median = 6), including FGFR1 amplification (n = 3), ERBB2 (HER2) amplification (n = 2). PIK3CA amplification occurred in combination with either FGFR1 or ERBB2 (HER2) amplification (n = 1 each), or alone (n = 1). In the Adeno and NSCLC-NOS groups combined, 91% of pts (61/68) had variants identified (range: 1-12 variants, median = 3), of which 42% (26/62) had at least one of the seven NCCN recommended lung adenocarcinoma genomic targets (EGFR (21%), EML4-ALK (8.1%), ERBB2 exon 20 insertion (6%), MET Amp (3.2%), ROS1 (2%), BRAF V600E (2%)). Concurrent detection of driver and resistance mutations were identified in 6/13 patients with EGFR driver mutations (T790M (n = 1), T790M/C797S (n = 1), MET amp (n = 2), T790M/MET amp (n = 1) and ERBB2 amp (n = 1)) and in 3/5 patients with EML4-ALK fusion (MET exon 14 skipping (n = 1) and the ALK L1196M gatekeeper mutation (n = 2)).
Conclusions
Genomic profiling utilizing ctDNA analysis detected alterations in majority of advanced NSCLC pts, with targetable aberrations and resistance mechanisms identified. This approach has prompted changes in matched therapy in selected pts, and has demonstrated its feasibility in Asia.
Clinical trial identification
Legal entity responsible for the study
The Chinese University of Hong Kong
Funding
None
Disclosure
H. Loong: Advisory Board: Celgene, Novartis, Roche Travel Support: BMS, MSD, Novartis, Roche, TaiHo Speakers\' Bureau: Abbvie, Novartis Research Funding: MSD, Mundipharma, V. Raymond: Employee of Guardant Health. T. Yung: Employee of Sanomics Limited. R.B. Lanman: Employee and shareholder of Guardant Health. S. Skrzypczak: Employee of Guardant Health, T.S.K. Mok: Shareholder of Sanomics Limited.
All other authors have declared no conflicts of interest.