Epithelial to mesenchymal markers and clinical outcomes on erlotinib in stage IV non-small cell lung cancer patients.

e19117 Background: An epithelial phenotype in NSCLC is associated with improved sensitivity to EGFR tyrosine kinase inhibitors (TKI). The best method to identify this subset is unknown (Richardson Anticancer Research 2012, Byers Clin Cancer Res 2012). This retrospective study correlates E-cadherin (Ecad) and vimentin (vim) immunohistochemistry (IHC) expression with outcomes in advanced NSCLC patients (pts) treated with erlotinib (E). Methods: Advanced NSCLC pts that received E were included if sufficient tumor was available from diagnosis. IHC scores for E-cad and vim were generated by multiplying frequency (0-4) by intensity (0-4). Log Rank was used to correlate IHC expression with progression free and overall survival (PFS, OS). Results were compared to a subset of pts with tissue from primary surgical NSCLC resection who later received E for recurrent disease. Results: 159 advanced NSCLC pts treated with E had tissue from diagnosis and IHC analysis. There was no correlation with PFS or OS on E and high/low vim or Ecad expression. Subtracting the IHC scores (vim minus ecad) created a difference score. A low difference score (n = 62) correlated with prolonged PFS (2.6 vs 1.9 months, p = .014 HR 1.52) compared with a high score, n = 97. Low difference score trended toward prolonged OS (p=.46) 33 of the patients had tissue available from primary surgical resection. The invasive front was examined for membranous E-cad and cytoplasmic vim (Allred score 0-8). Patients with low vim (< 4) and Ecad (>5), n= 19, trended toward prolonged PFS and OS on E compared with patients with high vim (>5) and low Ecad (<6), n=10 (4.2 vs 1.6 months and 15.5 vs 6.5 months, respectively, p=NS). Conclusions: In this retrospective analysis, using unselected, frequently small tissue specimens, the expression of ecad or vim alone by IHC did not correlate with outcomes for E treated patients. A complicated difference score (vimentin score minus ecadherin score) did correlate with PFS on E. Examining EMT markers at the invasive edge of resected NSCLC tumors might more accurately assess EMT activity and its relationship to outcomes when these pts are recommended EGFR-TKIs.

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Detection of TP53 Mutations in Tissue or Liquid Rebiopsies at Progression Identifies ALK+ Lung Cancer Patients with Poor Survival

Cancers ◽

10.3390/cancers11010124 ◽

2019 ◽

Vol 11 (1) ◽

pp. 124 ◽

Cited By ~ 9

Author(s):

Petros Christopoulos ◽

Steffen Dietz ◽

Martina Kirchner ◽

Anna-Lena Volckmar ◽

Volker Endris ◽

...

Keyword(s):

Lung Cancer ◽

Kinase Inhibitors ◽

Stage Iv ◽

Progression Free Survival ◽

Resistance Mechanisms ◽

Wild Type ◽

Tp53 Mutations ◽

Lung Cancer Patients ◽

Anaplastic Lymphoma ◽

Nsclc Patients

Anaplastic lymphoma kinase (ALK) sequencing can identify resistance mechanisms and guide next-line therapy in ALK+ non-small-cell lung cancer (NSCLC), but the clinical significance of other rebiopsy findings remains unclear. We analysed all stage-IV ALK+ NSCLC patients with longitudinally assessable TP53 status treated in our institutions (n = 62). Patients with TP53 mutations at baseline (TP53mutbas, n = 23) had worse overall survival (OS) than patients with initially wild-type tumours (TP53wtbas, n = 39, 44 vs. 62 months in median, p = 0.018). Within the generally favourable TP53wtbas group, detection of TP53 mutations at progression defined a “converted” subgroup (TP53mutconv, n = 9) with inferior OS, similar to that of TP53mutbas and shorter than that of patients remaining TP53 wild-type (TP53wtprogr, 45 vs. 94 months, p = 0.043). Progression-free survival (PFS) under treatment with tyrosine kinase inhibitors (TKI) for TP53mutconv was comparable to that of TP53mutbas and also shorter than that of TP53wtprogr cases (5 and 8 vs. 13 months, p = 0.0039). Fewer TP53wtprogr than TP53mutbas or TP53mutconv cases presented with metastatic disease at diagnosis (67% vs. 91% or 100%, p < 0.05). Thus, acquisition of TP53 mutations at progression is associated with more aggressive disease, shorter TKI responses and inferior OS in ALK+ NSCLC, comparable to primary TP53 mutated cases.

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First-line therapy and methylation status of CHFR in serum influence outcome to chemotherapy versus EGFR tyrosine kinase inhibitors as second-line therapy in stage IV non-small-cell lung cancer patients

Lung Cancer ◽

10.1016/j.lungcan.2010.07.008 ◽

2011 ◽

Vol 72 (1) ◽

pp. 84-91 ◽

Cited By ~ 21

Author(s):

Fernanda Salazar ◽

Miguel Angel Molina ◽

Maria Sanchez-Ronco ◽

Teresa Moran ◽

Jose Luis Ramirez ◽

...

Keyword(s):

Kinase Inhibitors ◽

Methylation Status ◽

Stage Iv ◽

Small Cell Lung ◽

First Line ◽

Second Line Therapy ◽

Lung Cancer Patients ◽

First Line Therapy ◽

Line Therapy ◽

Egfr Tyrosine Kinase Inhibitors

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Outcome of advanced NSCLC patients harboring sensitizing EGFR mutations randomized to EGFR tyrosine kinase inhibitors or chemotherapy as first-line treatment: a meta-analysis

Annals of Oncology ◽

10.1093/annonc/mdq742 ◽

2011 ◽

Vol 22 (10) ◽

pp. 2277-2285 ◽

Cited By ~ 57

Author(s):

E. Bria ◽

M. Milella ◽

F. Cuppone ◽

S. Novello ◽

A. Ceribelli ◽

...

Keyword(s):

Tyrosine Kinase ◽

Kinase Inhibitors ◽

Advanced Nsclc ◽

Meta Analysis ◽

Egfr Mutations ◽

Line Treatment ◽

First Line ◽

Egfr Tyrosine Kinase Inhibitors ◽

Nsclc Patients ◽

First Line Treatment

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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

Cancers ◽

10.3390/cancers13102425 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2425

Author(s):

Paolo Bironzo ◽

Maria Lucia Reale ◽

Tessa Sperone ◽

Fabrizio Tabbò ◽

Andrea Caglio ◽

...

Keyword(s):

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Tyrosine Kinase ◽

Kinase Inhibitors ◽

Egfr Mutation ◽

Advanced Nsclc ◽

Growth Factor Receptor ◽

Epidermal Growth ◽

Nsclc Patients

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.

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