Clinical Utility and Outcomes Impact of Crystal Digital PCR of Sensitizing and Resistance EGFR Mutations in Patients With Advanced Non-Small Cell Lung Cancer

Prospective collection of 252 blood samples in 140 patients with EGFR-mutant non-small cell lung cancer to evaluate detection of EGFR mutations by Crystal digital PCR liquid biopsy. The overall detection rate was around 50%, but variable depending on the disease burden, reflecting the impact of the patient disease profile when interpreting results. Background: EGFRm represent 15% of advanced NSCLC in European patients. LB for molecular profiling offers a noninvasive alternative to tissue. cdPCR is a high-sensitive and low-cost LB to detect molecular alterations. We aimed to describe cdPCR clinical utility for EGFRm detection in advanced NSCLC. Methods: Prospective blood sample collection in patients with advanced NSCLC harbouring EGFRm either at diagnosis, under response or at PD between January 16 and September 20 at Gustave Roussy. LB was performed by cdPCR (Stilla): sensitizing (exon19; exon21 [p.L858R]) and exon 20 p.T790M resistance EGFRm. We defined high tumour burden (high-TB) as ,2 metastatic sites. We analysed EGFRm detection by cdPCR and its correlation with progression-free and overall survival (PFS, OS). Results: A total of 252 blood samples were collected in 140 patients. At baseline (n=25), sensitizing EGFRm were detected in 64% of samples, 88% in patients with high-TB (n=8) and 40% among those with intracranial/intrathoracic isolated lesions (n=5). At PD to tyrosine-kinase inhibitors (TKI) (n=117), detection rate (sensitizing EGFRm) was 56%; 30% in patients with intracranial/thoracic isolated lesions (n=37) vs. 67% in those with high-TB (n=63). At PD to first/second generation TKI (n=81), the p.T790M mutation was found in 22% (18/81); detection rate was 9% for intracraniaVthoracic (n=23) vs. 32% for high-TB (n=41) cases. The clearance of EGFFlm allelic frequency was correlated with radiological response. The absence of EGFRm detection at TKI-failure was associated with longer OS (39.1 vs. 18.4 months; P=.02). Conclusions: cdPCR is a sensitive LB for sensitizing and resistance EGFRm detection. cdPCR positivity was more likely observed in systemic PD cases with high-TB. It is a low-cost EGFRm detecting approach to guide treatment in NSCLC, however metastatic profile should be taken into account. (C) 2022 Elsevier Inc. All rights reserved.

Automated summary

This study aimed to evaluate the detection of EGFR mutations by Crystal digital PCR (cdPCR) liquid biopsy and explore its clinical utility in advanced non-small cell lung cancer (NSCLC). The results showed that cdPCR is a sensitive method for detecting both sensitizing and resistance EGFR mutations. Positive cdPCR results were more likely to occur in cases with high tumor burden. Therefore, cdPCR is a low-cost approach for EGFR mutation detection that can guide the treatment of NSCLC.