Abstract 1274P
Background
Liquid biopsy is a useful diagnostic tool for advanced/metastatic NSCLC especially when tissue is inadequate for molecular testing and for detection of resistance mechanisms in EGFR mutated patients (pts). Experience with liquid biopsies for advanced/metastatic NSCLC pts in resource constrained settings is sparse.
Methods
Retrospective audit of liquid biopsies performed for NSCLC pts at a tertiary care referral centre in India over a 50-month period (February 2017 to April 2021). Testing methods included digital droplet PCR (ddPCR) and Next Generation Sequencing (NGS). ddPCR was used to detect specific EGFR mutations (L858R exon 21, E746_A750 exon 19 deletions & T790M exon 20) in ctDNA with limit of detection based upon amplifiable DNA ranging from 0.5% to <0.01% of mutant allele. For NGS, cfDNA was extracted from plasma, subjected to target enrichment by high multiplex PCR amplification and subsequently mutation analysis using panel of genes (BRAF, EGFR, ERBB2/HER2, KRAS, MET) on the Ion Proton semiconductor sequencer (Life Technology, USA). Herein, exosomal mRNA using the same platform was also analyzed for fusions in ALK, ROS1 and RET genes. Minimum 20000 reads were required for fusion gene analysis. Descriptive statistics are used.
Results
137 liquid biopsies were performed in 128 pts [51% males; median age 60 years] during this period. ddPCR and NGS were performed in 99 (72%) and 38 (28%) pts respectively. Timing was prior to/during first-line treatment (1L Rx) in 47 (34%) and at progression (PD) on 1L Rx in 90 (66%) pts. Most common indications for liquid biopsy were inadequate tissue for molecular analysis (n=31; 18 ddPCR / 13 NGS) in the former and PD in EGFR mutated pts (n=81; 73 ddPCR / 8 NGS) in the latter where T790M detection rate was 35% (n=28). For the primary EGFR sensitizing mutation, concordance between tissue and liquid biopsies was 61% while sensitivity of liquid biopsy was 57%. NGS LB detected EGFR mutations in 3 pts missed on tissue. Potential change in management with use of liquid biopsies was 26% overall and 34% when done at PD.
Conclusions
In resource constrained settings, greatest utility of liquid biopsies is for EGFR mutated NSCLC pts with PD on 1st/2nd generation EGFR-TKIs wherein T790M detection can avoid rebiopsy in almost 1/3 pts.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.