1430PCell-free circulating tumour DNA (ctDNA) in the management of patients with non-biopsiable advanced non-small cell lung cancer (NSCLC)

Background: Genomic profiling of cell-free ctDNA is a non-invasive method to guide personalised medicine. We assessed the utility of ctDNA in routine clinical practice where tumor biopsy were impossible to obtain, tissue insufficient or clinically contraindicated. Methods: A 73-gene panel using ctDNA NGS (Guardant360®) was offered to consecutive stage 4 NSCLC patients - results were discussed in our Genomics Review Board to assess potential actionable alterations and enrolment into clinical trials. Results: 50 pts (37F:13M; median 64 yrs) participated. ctDNA was obtained in 6 treatment (Tx) naïve patients (pts), in 22pts post 1st-line, in 7pts post 2nd-line, in 5 pts post 3rd-line and in 5 pts with > 4 Tx – in 5 pts prior Tx was unknown. EGFR status at Dx was known in 40 (23mt/17wt) and unknown in 10 pts. Of the pts with known EGFRmt, 6 pts progressed on gefitinib, 7 pts on afatinib, 8 pts on erlotinib, and 2 pts did not receive prior anti-EGFR Tx. ctDNA testing confirmed EGFRmt in 14 pts. In 9 pts with previously Bx-proven EGFRmt ctDNA did not detect an EGFRmt - the lag time between Bx and ctDNA was a median of 18 months (range 1-94 months). New EGFRmt were found in 3 pts with unknown EGFR status allowing access to anti-EGFR Tx. Acquired T790M were found in 4 pts progressing on prior anti-EGFR Tx, those pts received osimertinib. In 1 pt with ctDNA T790M+, a concomitant solid Bx was T790M-. Other alterations were, TP53 (n = 23), KRAS (n = 7), ERBB2 (n = 1), NTRK1 (n = 2), NF1 (n = 12), MET (n = 7), BRAF (n = 5), PIK3CA (n = 5), ALK (n = 2), BRCA1 (n = 1), BRCA2 (n = 2), PDGFRA (n = 3), AR (n = 4), TERT (n = 3), CDK4 (n = 3), CDK6 (n = 3), FGFR2 (n = 2), STK11 (n = 2), KIT (n = 2), SMAD4 (n = 3), CDH1 (n = 1), NOTCH1 (n = 2), RB1 (n = 3), TSC1 (n = 1), ERBB1(n = 1), MTOR (n = 3), MYC (n = 3), ARAF (n = 1), GNAS (n = 1), AKT1(n = 1), CDKN2A (n = 2), ARID1A (n = 2), CTNNB1 (n = 1), CCNE1 (n = 1). Critical review in the GRB meeting was fundamental in interpreting the genetic alterations of significance. Conclusions: We confirm the feasibility and clinical utility of ctDNA testing in NSCLC patients where tumor biopsies were insufficient, impossible or contraindicated and identified 7 pts (14%) who based on their ctDNA results received 1st/2nd-line anti-EGFR treatment, several more were recommended for clinical trials. Legal entity responsible for the study: Sarah Cannon Research Institute. Funding: Has not received any funding. Disclosure: P. Bennett: Employee: Sarah Cannon Molecular Diagnostics. I. Faull, R.B. Lanman: Employee: Guardant. All other authors have declared no conflicts of interest.