Abstract 1353P
Background
Advances in targeted therapeutics has increased the need for biomarker testing in mNSCLC. Relative benefits of ctDNA NGS for target identification over current standard tissue and single gene ctDNA genotyping outside clinical trials are not fully understood.
Methods
Case notes for patients (pts) with mNSCLC undergoing ctDNA NGS (Guardant360™ 74 gene panel) as part of routine care at a single centre were reviewed. ctDNA NGS was performed for up front target identification or at acquired TKI resistance. Variants were tiered according to AMP/ASCO/CAP guidelines. Primary objective: proportion of informative ctDNA NGS tests, defined as reporting any genomic variant.
Results
Of 54 ctDNA NGS tests from 47 pts, 30/34 (88%) were informative in the upfront setting, 18/20 (90%) in the resistance setting. In the upfront setting, number of Tier I variants identified increased by 69% (13 to 22 pts) when ctDNA NGS was performed in addition to tissue testing. In the TKI resistance setting, ctDNA NGS identified a Tier I resistance variant in 35% (7/20), compared to 15% (3/20) with standard tissue testing alone. 78% of non-informative or false negative ctDNA NGS tests occurred in patients with pulmonary or CNS only disease. Time from sampling to report was shorter for ctDNA NGS than tissue genotyping (9 vs. 18 days, p=0.0015). Table: 1353P
Patient characteristics n=47
| Median age at diagnosis (range) | 61 (31-79) | % |
| n | ||
| Sex | ||
| Male | 16 | 34 |
| Female | 31 | 66 |
| Smoking | ||
| Never | 25 | 53 |
| Ex/current | 22 | 47 |
| Histology | ||
| Adenocarcinoma | 44 | 94 |
| Pleomorphic | 2 | 4 |
| Squamous | 1 | 2 |
| M Stage at time of ctDNA NGS | ||
| M1A | 13 | 28 |
| M1B | 5 | 11 |
| M1C | 29 | 62 |
| Metastases | ||
| CNS only | 4 | 9 |
| Pulmonary only | 12 | 26 |
| Known tissue variants at ctDNA NGS | ||
| N | 28 | 60 |
| Y | 19 | 40 |
| EGFR Del19 | 11 | 23 |
| EGFR L858R | 1 | 2 |
| EML4-ALK fusion | 1 | 2 |
| ROS1 fusion | 1 | 2 |
| TP53 variant | 1 | 2 |
| EGFR Del19, T790M | 1 | 2 |
| EGFR Del19, T790M, C797S | 1 | 2 |
| EGFR Del19, EGFR Ins20 | 1 | 2 |
| EGFR Ins20 | 1 | 2 |
Conclusions
We demonstrate the utility of ctDNA NGS as complementary to standard molecular genotyping in mNSCLC, by increasing the proportion of patients identified with actionable variants and halving time to results. Appropriate patient and technology selection is key to ensure maximal clinical benefit.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
I. Faull: Leadership role, Shareholder/Stockholder/Stock options, Senior Director Medical Affairs and BD Europe: Guardant Health; Leadership role, senior sales manager diagnostics, EMEA: Nanostring technologies; Leadership role, Consultant for Spain and EU: 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. 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, Speaker Bureau/Expert testimony: AbbVie; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Boehringer Ingelheim; Speaker Bureau/Expert testimony: 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; Non-remunerated activity/ies, chair of steering committee: BTOG; Non-remunerated activity/ies, scientific faculty member 2015 - 2019: ESMO annual congress lung cancer; Non-remunerated activity/ies: ESMO Asia congress lung cancer track; Non-remunerated activity/ies: ESMO advanced course EGFR mutant NSCLC; Non-remunerated activity/ies, 2017-2019: ELCC congress scientific faculty ; Non-remunerated activity/ies: ETOP Foundation council member; Non-remunerated activity/ies: EORTC lung cancer group member. All other authors have declared no conflicts of interest.