Resumen de MET overexpression correlated with prognosis of EGFR‑mutant treatment‑naïve advanced lung adenocarcinoma: a real‑world retrospective study

Na Wang, Junhua Wu, Bo Huang, Jun Fan, Xiu Nie, Yuan Zhang, Yili Zhu, Ying Wu, Ruiguang Zhang

• Background About 50–60% treatment-naïve advanced non-small-cell lung cancers were coexistence of epidermal growth factor receptor (EGFR) and mesenchymal epithelial transition (MET) overexpression. However, few studies demonstrated the prognostic value of MET protein expression in untreated EGFR-mutant lung adenocarcinoma (LUAD).

  Methods A total of 235 EGFR-mutant untreated advanced LUAD patients were retrospectively enrolled. MET expression was determined using immunohistochemistry, and MET positivity was defned as 2+or 3+using the METmab scoring algorithm. Progression-free survival (PFS) and overall survival (OS) were analysed according to MET expression status. Independent factors predicting prognosis were identifed using multivariate Cox regression analyses.

  Results Of the 235 patients, 113 (48.1%) harboured exon 19 deletion (19_del), 103 (43.8%) had exon 21 L858R mutations, and 19 (8.1%) had other mutation types, including exon 21 L861Q, exon 18 G719A/C, exon 20 S768I, and L858R/19_del double mutations. MET-positive expression was observed in 192 (81.7%) cases. There was no signifcant diference in baseline clinicopathological characteristics between MET positivity and MET negativity groups. Patients were stratifed by diferent EGFR mutation subtypes. MET-positive patients in the L858R mutation subgroup had markedly shorter PFS and OS than MET-negative patients (median PFS: 13 versus 27.5 months, p<0.001; median OS: 29 versus not reached, p=0.008), but no signifcant diference was observed in the 19_del subgroup. Multivariate Cox regression analyses indicated that MET positivity was an independent predictor for poor PFS and OS in L858R subgroup (PFS: HR=3.059, 95% CI 1.552–6.029, p=0.001; OS: HR=3.511, 95% CI 1.346–9.160, p=0.010). Additionally, an inferior survival outcome of MET positivity was observed in the L858R mutation subgroup when treated with EGFR–tyrosine kinase inhibitor (TKI) monotherapy as the frst-line regimen (median PFS: 13 versus 36.5 months, p<0.001; median OS: 29 versus not reached, p=0.012) but not with EGFR–TKI plus platinum doublet chemotherapy.

  Conclusions MET positive expression was an independent predictor of poor outcomes in untreated EGFR L858R mutation advanced LUAD patients treated with frst-line EGFR–TKI monotherapy