Background: Tyrosine kinase inhibitors (TKIs) show variable efficacy in epidermal growth factor receptor mutation‐positive (EGFR+) NSCLC patients, even in patients harbouring the same mutation. Co‐alterations may predict different outcomes to TKIs. Methods: We retrospectively analysed all consecutive EGFR+ advanced NSCLC treated with first‐line TKIs at our Institutions. NGS with a 22 genes clinical panel was performed on diagnostic specimens. PD‐L1 expression was also evaluated. Results: Of the 106 analysed specimens, 59 showed concomitant pathogenic mutations. No differences in OS (mOS 22.8 vs. 29.5 months; p = 0.088), PFS (mPFS 10.9 vs. 11.2 months; p = 0.415) and ORR (55.9% vs. 68.1%; p = 0.202) were observed comparing patients without and with co‐alterations. Subgroup analysis by EGFR mutation type and TKIs generation (1st/2nd vs. 3rd) did not show any difference too. No correlations of PD‐L1 expression levels by co-mutational status were found. Significant associations with presence of co‐alterations and younger age (p = 0.018) and baseline lymph nodes metastases (p = 0.032) were observed. Patients without concomitant alterations had a significant higher risk of bone progression (26.5% vs. 3.3%, p = 0.011). Conclusions: Pathogenic co‐alterations does not seem to predict survival nor efficacy of EGFR TKIs in previously untreated advanced NSCLC.

Clinical and molecular features of epidermal growth factor receptor (Egfr) mutation positive non‐small‐cell lung cancer (nsclc) patients treated with tyrosine kinase inhibitors (tkis): Predictive and prognostic role of co‐mutations

Bironzo P.;Reale M. L.;Sperone T.;Tabbo F.;Caglio A.;Passiglia F.;Di Maio M.;Righi L.;Bussolino F.;Scagliotti G. V.;Novello S.
2021-01-01

Abstract

Background: Tyrosine kinase inhibitors (TKIs) show variable efficacy in epidermal growth factor receptor mutation‐positive (EGFR+) NSCLC patients, even in patients harbouring the same mutation. Co‐alterations may predict different outcomes to TKIs. Methods: We retrospectively analysed all consecutive EGFR+ advanced NSCLC treated with first‐line TKIs at our Institutions. NGS with a 22 genes clinical panel was performed on diagnostic specimens. PD‐L1 expression was also evaluated. Results: Of the 106 analysed specimens, 59 showed concomitant pathogenic mutations. No differences in OS (mOS 22.8 vs. 29.5 months; p = 0.088), PFS (mPFS 10.9 vs. 11.2 months; p = 0.415) and ORR (55.9% vs. 68.1%; p = 0.202) were observed comparing patients without and with co‐alterations. Subgroup analysis by EGFR mutation type and TKIs generation (1st/2nd vs. 3rd) did not show any difference too. No correlations of PD‐L1 expression levels by co-mutational status were found. Significant associations with presence of co‐alterations and younger age (p = 0.018) and baseline lymph nodes metastases (p = 0.032) were observed. Patients without concomitant alterations had a significant higher risk of bone progression (26.5% vs. 3.3%, p = 0.011). Conclusions: Pathogenic co‐alterations does not seem to predict survival nor efficacy of EGFR TKIs in previously untreated advanced NSCLC.
2021
13
10
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Co‐mutations; Epidermal growth factor receptor (EGFR); Next‐generation sequencing (NGS); Non‐small‐cell lung cancer (NSCLC); Tyrosine kinase inhibitors (TKIs)
Bironzo P.; Reale M.L.; Sperone T.; Tabbo F.; Caglio A.; Listi A.; Passiglia F.; Di Maio M.; Righi L.; Bussolino F.; Scagliotti G.V.; Novello S.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1790638
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