Circulating tumour DNA (ctDNA) is an emerging non-invasive method to guide personalised medicine in patients (pts) with advanced non-small cell lung cancer (NSCLC). The aim of this project was to assess the utility of ctDNA in routine clinical practice where tumour biopsy (Bx) was contraindicated or insufficient for genotyping.
A 73-gene cancer panel test using next generation sequencing for ctDNA profiling (Guardant360®) was offered at our institution to stage IV NSCLC pts. The reports obtained were discussed in a multidisciplinary Genomics Review Board (GRB) to assess potentially actionable genomic alterations and enrolment into clinical trials. All pts consented for prospective collection of demographic, clinical, and biomolecular data.
Thirty advanced lung cancer pts were offered ctDNA testing. Histology included adeno- in 27 (90%) pts, squamous cell- in 2 (7%) pts, and small cell carcinoma in 1 (3%) pt. As assessed by baseline tumour Bx, EGFR status was mutant in 15 (50%) pts, wild type in 8 (27%) pts, and unknown in 7 (23%) pts. Activating EGFR mutations (mut) showed on original Bx at diagnosis were detected by ctDNA in 11 (73%) pts – lag-time 17 months (range 7-94). Primary EGFR mut were found in 2 pts with unknown EGFR status, allowing access to EGFR tyrosine kinase inhibitors (TKIs). Acquired T790M mut was found in 3 (20%) pts progressing on prior EGFR TKI, with the indication to receive Osimertinib. Only 1 pt with ctDNA-positive status for T790M mut received concomitant solid Bx which was negative for T790M mut. Other genomic alterations were detected in the overall population, more commonly involving TP53 (n = 12; 40%), NF1 (n = 7; 23%), MET (n = 5; 17%), BRAF (n = 4; 13%), PIK3CA (n = 3; 10%), BRCA 1/2 (n = 3; 10%), PDGFRA (n = 3; 10%), and AR (n = 3; 10%) genes. Critical review in the GRB was crucial in assessing genomic alterations of clinical significance.
Our study confirms the utility of ctDNA testing in advanced NSCLC pts where tumour Bx was not possible or insufficient for genotyping. Based on ctDNA, 5 pts received treatment with 1st- or 2nd-line EGFR TKIs while several pts were considered for clinical trial participation. Updated results of this ongoing study will be reported.
Clinical trial identification
Legal entity responsible for the study
Sarah Cannon Research Institute UK
R. Lanman, I. Faull: Affiliated to Guardant Health. All other authors have declared no conflicts of interest.