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.
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.
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.
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.
Clinical trial identification
Legal entity responsible for the study
Sarah Cannon Research Institute.
Has not received any funding.
P. Bennett: Employee: Sarah Cannon Molecular Diagnostics. I. Faull, R.B. Lanman: Employee: Guardant. All other authors have declared no conflicts of interest.