Background: Resistance to osimertinib in advanced EGFR-mutated non-small cell lung cancer (NSCLC) constitutes a significant challenge for clinicians either in terms of molecular diagnosis and subsequent therapeutic implications. Methods: This is a prospective single-centre study with the primary objective of characterising resistance mechanisms to osimertinib in advanced EGFR-mutated NSCLC patients treated both in first- and in second-line. Next-Generation Sequencing analysis was conducted on paired tissue biopsies and plasma samples. A concordance analysis between tissue and plasma was performed. Results: Sixty-five advanced EGFR-mutated NSCLC patients treated with osimertinib in first- (n = 56) or in second-line (n = 9) were included. We managed to perform tissue and liquid biopsies in 65.5% and 89.7% of patients who experienced osimertinib progression, respectively. Acquired resistance mechanisms were identified in 80% of 25 patients with post-progression samples, with MET amplification (n = 8), EGFR C797S (n = 3), and SCLC transformation (n = 2) the most frequently identified. The mean concordance rates between tissue and plasma for the EGFR activating mutation and for the molecular resistance mechanisms were 87.5% and 22.7%, respectively. Conclusions: Resistance to osimertinib demonstrated to be highly heterogeneous, with MET amplification the main mechanism. Plasma genotyping is a relevant complementary tool which might integrate tissue analysis for the study of resistance mechanisms.

Resistance to osimertinib in advanced EGFR-mutated NSCLC: a prospective study of molecular genotyping on tissue and liquid biopsies / Leonetti, A; Verzè, M; Minari, R; Perrone, F; Gnetti, L; Bordi, P; Pluchino, M; Nizzoli, R; Azzoni, C; Bottarelli, L; Lagrasta, C A M; Mazzaschi, G; Buti, S; Gasparro, D; Cosenza, A; Ferri, L; Majori, M; De Filippo, M; Ampollini, L; La Monica, S; Alfieri, R; Silini, E M; Tiseo, M. - In: BRITISH JOURNAL OF CANCER. - ISSN 0007-0920. - (2023). [10.1038/s41416-023-02475-9]

Resistance to osimertinib in advanced EGFR-mutated NSCLC: a prospective study of molecular genotyping on tissue and liquid biopsies

Leonetti, A;Minari, R;Gnetti, L;Bordi, P;Azzoni, C;Bottarelli, L;Lagrasta, C A M;Mazzaschi, G;Buti, S;Gasparro, D;Majori, M;De Filippo, M;Ampollini, L;La Monica, S;Alfieri, R;Silini, E M;Tiseo, M
2023-01-01

Abstract

Background: Resistance to osimertinib in advanced EGFR-mutated non-small cell lung cancer (NSCLC) constitutes a significant challenge for clinicians either in terms of molecular diagnosis and subsequent therapeutic implications. Methods: This is a prospective single-centre study with the primary objective of characterising resistance mechanisms to osimertinib in advanced EGFR-mutated NSCLC patients treated both in first- and in second-line. Next-Generation Sequencing analysis was conducted on paired tissue biopsies and plasma samples. A concordance analysis between tissue and plasma was performed. Results: Sixty-five advanced EGFR-mutated NSCLC patients treated with osimertinib in first- (n = 56) or in second-line (n = 9) were included. We managed to perform tissue and liquid biopsies in 65.5% and 89.7% of patients who experienced osimertinib progression, respectively. Acquired resistance mechanisms were identified in 80% of 25 patients with post-progression samples, with MET amplification (n = 8), EGFR C797S (n = 3), and SCLC transformation (n = 2) the most frequently identified. The mean concordance rates between tissue and plasma for the EGFR activating mutation and for the molecular resistance mechanisms were 87.5% and 22.7%, respectively. Conclusions: Resistance to osimertinib demonstrated to be highly heterogeneous, with MET amplification the main mechanism. Plasma genotyping is a relevant complementary tool which might integrate tissue analysis for the study of resistance mechanisms.
2023
Resistance to osimertinib in advanced EGFR-mutated NSCLC: a prospective study of molecular genotyping on tissue and liquid biopsies / Leonetti, A; Verzè, M; Minari, R; Perrone, F; Gnetti, L; Bordi, P; Pluchino, M; Nizzoli, R; Azzoni, C; Bottarelli, L; Lagrasta, C A M; Mazzaschi, G; Buti, S; Gasparro, D; Cosenza, A; Ferri, L; Majori, M; De Filippo, M; Ampollini, L; La Monica, S; Alfieri, R; Silini, E M; Tiseo, M. - In: BRITISH JOURNAL OF CANCER. - ISSN 0007-0920. - (2023). [10.1038/s41416-023-02475-9]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2963812
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