553P - Preceding plasma EGFR vs upfront tissue NGS for advanced NSCLC in the Chinese population: A single centre experience in Hong Kong

Background

Next generation sequencing (NGS) has revolutionised the diagnosis of non-small cell lung cancer (NSCLC) yet it is resource-intensive. Exclusionary testing followed by NGS has been advocated as a cost-effective approach in Asians where EGFR mutations are prevalent. Herein we investigated the approach of plasma EGFR (pEGFR) followed by tissue NGS and compared it to upfront tissue NGS in terms of mutation detection and clinical outcome in a real world setting in Hong Kong.

Methods

We retrospectively reviewed 222 patients diagnosed with advanced NSCLC from October 2021 to April 2023, including 145 cases that performed upfront tissue NGS without prior pEGFR (group 1) and 77 cases that underwent pEGFR (Cobas v2) first. Among the latter group, 48 with positive pEGFR (group 2a) started target therapy while 29 with negative pEGFR (group 2b) proceeded further tissue NGS (Oncomine precision assay). Genomic alterations and clinical data were compared among these approaches.

Results

The median age was 70, 72 and 76 years old for group 1, 2a and 2b respectively. Extrathoracic disease was found in 54%, 90% and 41% of patients in each group. Regarding genomic alterations detected by tissue NGS, sensitising EGFR mutations were found in 39% of cases in group 1, compared to only 7% in group 2b (OR 0.11, p=0.001). Additional driver mutations (EGFR exon 20 insertion, T790M, ALK, BRAF, MET exon 14 skipping, ERBB2 exon 20 insertion and KRAS) were found in 27% of group 1 cases, but up to 52% in group 2b (OR 2.92, p=0.008). For patients with EGFR mutations detected by tissue NGS, 41% had concurrent TP53 or PIK3CA mutation, which are predictive markers. The median time from radiological diagnosis to treatment initiation was 18 days for patients with positive pEGFR compared with 41 days for the counterparts underwent tissue NGS.

Conclusions

The pathway of pEGFR preceding tissue NGS allows early detection of druggable EGFR mutations and initiation of target therapy for patients with extrathoracic NSCLC but lacks simultaneous detection of predictive markers. The liquid-first approach enhances the yield of rare mutations by tissue NGS which is resource-dependent. It benefits regions where tissue biopsy is a rate limiting factor and EGFR mutations are prevalent.

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.