Abstract 1352P
Background
Advances in targeted therapy amplify the need for rapid comprehensive genotyping in NSCLC. Non-invasive NGS has shown high concordance with tissue NGS and faster turnaround times.
Methods
Guardant360™ (G360) ctDNA NGS was performed in consecutive patients (pts) with newly diagnosed or relapsed mNSCLC at RMH. Variants were tiered using AMP/ASCO/CAP guidelines. Results from Oct 19 - May 20 are described. Primary objective: proportion of informative G360 tests, defined as reporting any genomic variant.
Results
Of 50 pts included, G360 was informative in 44 (88%). 6 (12%) were uninformative. 19 (38%) identified a tier I variant; 8 (16%) were drugable: EGFR del19 (1); EGFR del19 + T790M (2), EGFR del19 + T790M + C797S (2), EGFR del19 + MET amplification (1), EGFR E709_T710delinsD exon 18 deletion (del18) (1), MET exon (ex) 14 skipping (1). 7/8 results changed management. G360 detected 18 additional tier I variants compared to tissue PCR and NGS alone; including 3 drugable variants: EGFR del18, MET ex14 skipping, EGFR del19 + T790M. Median time from request to report was shorter for G360 compared to tissue NGS (7 vs 21 d, p<0.0001). 3/19 (16%) pts required additional biopsy for tissue NGS. 8 of 15 (53%) available tissue NGS results were uninformative. 2/50 (4%) G360 tests were false negatives (EML4 ALK fusion, MET ex14 skipping). Table: 1352P
Pt characteristics
| All N (%) N = 50 | Informative ctDNA NGS N (%) N = 44 | |
| Age | ||
| Median (range) | 70 (41 – 98) | 69 (43 – 98) |
| Sex | ||
| Male | 30 (60) | 25 (57) |
| Female | 20 (40) | 19 (43) |
| Smoking | ||
| Never | 7 (14) | 6 (14) |
| Ex/current | 43 (86) | 38 (86) |
| Median pack years | 30 | 30 |
| Ethnicity | ||
| White | 42 (84) | 37 (84) |
| Asian | 8 (16) | 7 (16) |
| Diagnosis | ||
| New | 35 (70) | 32 (73) |
| Relapsed | 15 (30) | 12 (27) |
| Histology | ||
| Adenocarcinoma | 37 (72) | 33 (75) |
| Squamous cell | 8 (16) | 8 (18) |
| Other | 5 (10) | 3 (7) |
| Known variants before G360 | ||
| N | 42 (84) | |
| Y | 8 (16) | |
| KRAS G12C BRAF E586L EML4 ALK EGFR del19 EGFR L858R EGFR del19 + T790M | 1 (12) 1 (12) 1 (12) 2 (25) 1 (12) 2 (25) |
Conclusions
ctDNA NGS increased the detection of actionable genomic variants in a highly rapid and minimally invasive manner. With the exception of gene fusions and rare mutations, false negatives were low. Therefore, it is time to consider routine upfront use of ctDNA NGS for mNSCLC at diagnosis and relapse.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Guardant Health.
Disclosure
I. Faull: Leadership role, Shareholder/Stockholder/Stock options: Guardant Health; Leadership role: Nanostring technologies; Leadership role: Genomic Health. R.J. Nagy: Shareholder/Stockholder/Stock options, Full/Part-time employment: Guardant Health. S. Scott: Shareholder/Stockholder/Stock options, Full/Part-time employment: Guardant Health. A. Minchom: Honoraria (self): Loxo Oncology; Honoraria (self): Janssen Pharmaceuticals; Honoraria (self): Faron Pharmaceuticals; Honoraria (self): Bayer; Honoraria (self): Novartis; Honoraria (self): Merck Pharmaceuticals. S. Popat: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Takeda; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Speaker Bureau/Expert testimony: Chugai; Advisory/Consultancy: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): EMD Serono; Advisory/Consultancy: Guardant Health; Advisory/Consultancy: AbbVie; Advisory/Consultancy, Research grant/Funding (institution): Boehringer Ingelheim; Advisory/Consultancy: Medscape ; Advisory/Consultancy: Tesaro ; Speaker Bureau/Expert testimony: OncLive; Leadership role, Deputy Editor, Lung Cancer: Elsevier; Research grant/Funding (institution): Clovis Oncology; Research grant/Funding (institution): Eli Lilly; Research grant/Funding (institution): Epizyme; Research grant/Funding (institution): Ariad; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Synta. All other authors have declared no conflicts of interest.