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

Mariona Riudavets, Virginie Lamberts, Damien Vasseur, Edouard Auclin, Mihaela Aldea, Cécile Jovelet, Charles Naltet, Pernelle Lavaud, Anas Gazzah, Frank Aboubakar, Miriam Dorta, Jordi Remon, Etienne Rouleau, Maud Ngocamus, Claudio Nicotra, Ludovic Lacroix, Benjamin Besse, Laura Mezquita, David Planchard

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Background: EGFRm represent 15% of advanced NSCLC in European patients. LB for molecular profiling offers a non-invasive 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 intracranial/thoracic (n=23) vs. 32% for high-TB (n=41) cases. The clearance of EGFRm 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.

    Original languageEnglish
    Pages (from-to)e377-e383
    JournalClinical Lung Cancer
    Volume23
    Issue number6
    DOIs
    Publication statusPublished - 1 Sept 2022

    Keywords

    • Liquid biopsy
    • NSCLC
    • cdPCR
    • ctDNA
    • p.T790M resistance mutation

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