Abstract 1195P
Background
Liquid biopsy has been established as an important diagnostic step in identifying EGFR T790M resistance to 1st and 2nd generation EGFR TKIs. This has led to significant interest in exploring the value of liquid biopsy in patients with other oncogene-addicted cancers and acquired resistance to targeted therapy.
Methods
This study is being conducted at 6 Canadian centres (NCT03576937) using a validated cell-free DNA next-generation sequencing assay that identifies variants in 74 cancer-associated genes, including fusions and copy number gain (Guardant 360TM). In a discovery cohort (N=60), patients that failed targeted therapy for oncogene-addicted lung cancer receive a liquid biopsy (LB), paired with standard tumour tissue (TT) biopsy with molecular profiling if possible. Patients are required to have measurable disease (RECIST version 1.1), and, if failing a 1st or 2nd generation EGFR TKI, must demonstrate the absence of EGFR T790M in tissue (and plasma if standard of care). Exploratory analysis of incremental targetable alterations identified by LB is presented. Genomic alterations are categorized as actionable, (targeted therapy available for indication), potentially actionable (clinical trials available and/or known resistance mechanism) or non-actionable.
Results
56 of 60 patients have been enrolled. Median age of the cohort is 58 years (range 23-86), 36 (64%) are female, 48 (86%) are never smokers and all have adenocarcinoma. Seven (13%) patients have actionable targets and 9 (16%) potentially actionable targets identified through LB. Response data will be presented at the meeting.
Conclusions
Liquid biopsy provides a minimally invasive initial approach to the molecular characterization of resistance in patients with oncogene addicted lung cancer failing targeted therapy, yielding actionable or potentially actionable results in 20% of patients beyond EGFR T790M. Table: 1195P
| Oncogenic driver | N | Actionable Target in LB | Potentially Actionable | No. pts with Non-Actionable |
| ALK fusion* | 9 | 2 ALK G1202R 1 ALK C1156Y** | 1 EGFR amp | 6 |
| EGFR T790M- | 22 | 1 CCDC6-RET fusion1 MET amp**2 T790M | 1 KRAS G12D 1 CDK4 amp1 FGFR1 amp** | 17 |
| EGFR T790M+* | 20 | 1 MET amp1 BRAF V600E | 1 FGFR3-TACC fusion1 BRAF L597R 3 EGFR C797S** | 14 |
| ERBB2ins | 2 | -- | 2 | |
| MET ex14skip | 1 | 1 KRAS G12D | ||
| EGFR ex20ins | 1 | -- | 1 | |
| NRG fusion | 1 | 1 CCND2 amp1 EGFR amp** |
* ALK fusion+ pts received prior alectinib (median 3 prior TKI); EGFR T790M+ pts received prior osimertinib (median 2 prior TKI).**concurrent aberrations (G1202R+C1156Y; MET amp+ T790M; FGFR1 amp + CDK4 amp; C797S + BRAF; EGFR amp+CCND2 amp)
Clinical trial identification
NCT03576937.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Princess Margaret Cancer Foundation; Guardant Health.
Disclosure
L. Kiedrowski: Full/Part-time employment: Guardant Health. R.B. Lanman: Officer/Board of Directors: Guardant Health. N. Leighl: Research grant/Funding (self), Institutional grant: Guardant Health. All other authors have declared no conflicts of interest.