scholarly journals Predictive value of EGFR mutation in NSCLC patients treated with platinum doublet postoperative chemotherapy

2021 ◽  
Author(s):  
Toshiaki Takahashi ◽  
Kazuko Sakai ◽  
Hirotsugu Kenmotsu ◽  
Kiyotaka Yoh ◽  
Haruko Daga ◽  
...  
Keyword(s):  
Predictive Value ◽  
Egfr Mutation ◽  
Postoperative Chemotherapy ◽  
Nsclc Patients ◽  
Platinum Doublet

EGFR gene mutation and epithelial to mensenchymal transition (EMT) markers in advanced NSCLC patients treated with erlotinib.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18117-e18117
Author(s):  
Mary J. Fidler ◽  
Manish J Dave ◽  
Sanjib Basu ◽  
Thomas A. Hensing ◽  
Mark Pool ◽  
...  
Keyword(s):  
Negative Predictive Value ◽  
Gene Mutation ◽  
Predictive Value ◽  
Egfr Mutation ◽  
Nuclear Staining ◽  
Mesenchymal Transition ◽  
Egfr Gene ◽  
Nsclc Patients ◽  
Emt Markers ◽  
Egfr Gene Mutation

e18117 Background: TTF-1 is a transcription factor involved in regulating epithelial to mesenchymal transition (EMT). Previous work in a clinically enriched non-small cell lung cancer (NSCLC) population suggested low probability of an EGFR activating gene mutation in the absence of TTF-1 positivity (Somaiah ASCO 2011). This study's goal was to validate the relationship of TTF-1 and other immunohistochemical (IHC) markers of EMT to the presence of an EGFR activating gene mutation in a diverse group of NSCLC patients treated with erlotinib. Methods: Patients receiving erlotinib at two midwest institutions were retrospectively analyzed by IHC for TTF-1 (Greater than 5% of tumor cells with moderate (2+) or strong (3+) nuclear staining considered positive) and for PTEN, Ecadherin,vimentin, beta catinin, and snail (frequency(0-4) times intensity(0-4)). Exon 19 and L858R mutations were detectedusing single-strand conformation polymorphism and sequence-specific polymerase chain reaction (PCR)).Fisher’s exact testand logistic regression wereused to correlate TTF-1(positive or negative) and the remaining EMT markers with the presence of EGFR mutation. Results: 216 patients were analyzed for EGFR activating gene mutations: 15% squamous, 80% smokers. EGFR mutation was found in 11.6% of cases. TTF-1 was present in 8% of squamous cell patients and 71% of adenocarcinoma patients. TTF-1 correlated with prolonged progression free survival (log rank p=.004). TTF-1 positivity was strongly correlated with the presence of mutation (p=.0006, negative predictive value=97.7%). Increasing Ecadherin and increasing PTEN expression by IHC correlated with the presence of EGFR gene mutation when measured on continuum (p=.006 and p=.04, respectively). Conclusions: Though retrospective, our work confirms the negative predictive value of TTF-1 for an EGFR activating gene mutation in a NSCLC cohort representative of a North American population.Though high PTEN and Ecadherin expression also correlated with EGFR mutation, TTF-1 positivity may be a more straight-forward marker that can select patients who should be screened for the mutation prior to initiation of first line therapy.

scholarly journals The Prognostic Role of PORT and EGFR Mutation Status in Completely Resected Stage IIIA/N2 Non-Small Cell Lung Cancer Patients with Postoperative Chemotherapy

2021 ◽  
Vol 27 ◽  
Author(s):  
Hui Yang ◽  
Kunlun Wang ◽  
Shenglei Li ◽  
Yan Li ◽  
Ling Yuan
Keyword(s):  
Prognostic Factors ◽  
Egfr Mutation ◽  
Cox Regression ◽  
Postoperative Chemotherapy ◽  
Stage Iiia ◽  
Cox Regression Analysis ◽  
Complete Surgical Resection ◽  
Resected Stage ◽  
Nsclc Patients ◽  
Type Of Surgery

Background: The treatment choice for completely resected stage IIIA/N2 non-small cell lung cancer (NSCLC) patients is still controversial now. Our study aims to identify potential prognostic factors in stage IIIA/N2 NSCLC patients with complete surgical resection and postoperative chemotherapy.Methods: In this study, we screened the stage IIIA/N2 NSCLC patients diagnosed in the Affiliated Cancer Hospital of Zhengzhou University from 2015 to 2019. Completely resected patients with postoperative chemotherapy (PCT) were enrolled. The univariate and multivariate COX proportional hazards regression analyses were used to identify the prognostic factors. The Kaplan-Meier survival curve was used to compare the disease-free survival (DFS) and overall survival (OS) in the subgroup analyses.Results: 180 patients were collected, including 142 patients with PCT treatment alone and 38 patients with postoperative radiotherapy (PORT) treatment. The median DFS was 17.8 months (95% CI: 16.5–19.1 months) and the median OS was 50.6 months (47.4–53.9 months) in all the patients. The median DFS of the PORT group was significantly longer than the PCT group (38.7 vs 16.7 months, p < 0.001). Epidermal growth factor receptor (EGFR) mutation-positive patients had a worse DFS compared with EGFR mutation-negative patients (16.8 vs 18.0 months, p = 0.032). Possible prognostic factors were evaluated through univariate COX regression analysis. The further multivariate COX regression analysis showed that patients with PORT (HR: 0.318, 95% CI: 0.185–0.547, p < 0.001), EGFR mutation-negative (HR: 0.678, 95% CI: 0.492–0.990, p = 0.044), T1 (HR: 0.661, 95% CI: 0.472–0.925, p = 0.016), and lobectomy (HR: 0.423, 95% CI: 0.191–0.935, p = 0.034), had better DFS. The only independent prognostic factor of OS was the type of surgery (p = 0.013).Conclusion: PORT might improve the DFS of stage IIIA/N2 NSCLC patients with complete surgical resection and PCT, but it cannot increase OS. Besides, EGFR mutation status, T stage, and type of surgery are possible independent prognostic factors for DFS, and type of surgery is associated with OS. These factors remain to be clarified in further studies.

scholarly journals A phase II study of cisplatin plus vinorelbine combined with atezolizumab as adjuvant therapy for completely resected non-small-cell lung cancer with EGFR mutation (West Japan Oncology Group 11719L/ADJUST study)

2021 ◽  
Vol 13 ◽  
pp. 175883592098764
Author(s):  
Ryota Shibaki ◽  
Hiroaki Akamatsu ◽  
Terufumi Kato ◽  
Kazumi Nishino ◽  
Morihito Okada ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adjuvant Therapy ◽  
Egfr Mutation ◽  
Phase Ii Study ◽  
Small Cell ◽  
Small Cell Lung ◽  
Resected Nsclc ◽  
Egfr Mutated ◽  
Doublet Chemotherapy ◽  
Platinum Doublet

Background: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) is a standard treatment in EGFR-mutated advanced non-small-cell lung cancer (NSCLC); however, previous data have suggested that EGFR-TKI has limited potential as adjuvant therapy. On the contrary, based on subset analysis with the immune checkpoint inhibitor (ICI) plus platinum-doublet chemotherapy in advanced NSCLC with EGFR mutation, we hypothesized that this combination was worth testing as adjuvant therapy in patients with EGFR-mutated NSCLC. Methods: Herein, we introduce our phase II study of cisplatin plus vinorelbine combined with atezolizumab as adjuvant therapy for completely resected NSCLC with EGFR mutation. Accrued patients will be pathological stage II–IIIA with completely resected NSCLC and whose tumors have EGFR mutation. Treatment comprises four cycles of cisplatin plus vinorelbine combined with atezolizumab followed by maintenance with atezolizumab. The primary endpoint is the disease-free survival (DFS) rate at 2 years. Secondary endpoints are DFS, overall survival, and safety. In total, 18 patients will be enrolled in this study. Discussion: Ongoing phase III trials of adjuvant ICI allow the inclusion of patients with EGFR mutation, but our current trial will provide the earliest clinical data on the efficacy of platinum-doublet chemotherapy with atezolizumab.

scholarly journals 140P Prognostic and predictive value of co-mutational profile in advanced EGFR positive NSCLC patients treated with TKIs

2021 ◽  
Vol 16 (4) ◽  
pp. S773
Author(s):  
M.L. Reale ◽  
P. Bironzo ◽  
L. Righi ◽  
A. Listi ◽  
F. Tabbò ◽  
...  
Keyword(s):  
Predictive Value ◽  
Nsclc Patients

scholarly journals 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 ◽  
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.

Emergence of RET rearrangement co-existing with activated EGFR mutation in EGFR -mutated NSCLC patients who had progressed on first- or second-generation EGFR TKI

Lung Cancer ◽  
2015 ◽  
Vol 89 (3) ◽  
pp. 357-359 ◽  
Author(s):  
Samuel J. Klempner ◽  
Lyudmila A. Bazhenova ◽  
Fadi S. Braiteh ◽  
Petros G. Nikolinakos ◽  
Kyle Gowen ◽  
...  
Keyword(s):  
Second Generation ◽  
Egfr Mutation ◽  
Ret Rearrangement ◽  
Nsclc Patients ◽  
Egfr Mutated ◽  
Egfr Tki

scholarly journals P2.05-030 WBRT Prior EGFR TKIs is Effective Treatment Option for NSCLC Patients with CNS Metastases Harboring EGFR Mutation

2017 ◽  
Vol 12 (1) ◽  
pp. S1048-S1049
Author(s):  
Pawel Krawczyk ◽  
Marcin Nicoś ◽  
Dariusz Kowalski ◽  
Rodryg Ramlau ◽  
Kinga Winiarczyk ◽  
...  
Keyword(s):  
Effective Treatment ◽  
Treatment Option ◽  
Egfr Mutation ◽  
Cns Metastases ◽  
Effective Treatment Option ◽  
Nsclc Patients ◽  
Egfr Tkis

scholarly journals R-Score: A New Parameter to Assess the Quality of Variants’ Calls Assessed by NGS Using Liquid Biopsies

Biology ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 954
Author(s):  
Roberto Serna-Blasco ◽  
Estela Sánchez-Herrero ◽  
María Berrocal Renedo ◽  
Silvia Calabuig-Fariñas ◽  
Miguel Ángel Molina-Vila ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
False Negative ◽  
Digital Pcr ◽  
Liquid Biopsies ◽  
Molecular Alterations ◽  
Significant Linear Correlation ◽  
Molecular Landscape ◽  
Nsclc Patients ◽  
Next Generation Sequencing Ngs

Next-generation sequencing (NGS) has enabled a deeper knowledge of the molecular landscape in non-small cell lung cancer (NSCLC), identifying a growing number of targetable molecular alterations in key genes. However, NGS profiling of liquid biopsies risk for false positive and false negative calls and parameters assessing the quality of NGS calls remains lacking. In this study, we have evaluated the positive percent agreement (PPA) between NGS and digital PCR calls when assessing EGFR mutation status using 85 plasma samples from 82 EGFR-positive NSCLC patients. According to our data, variant allele fraction (VAF) was significantly lower in discordant calls and the median of the absolute values of all pairwise differences (MAPD) was significantly higher in discordant calls (p < 0.001 in both cases). Based on these results, we propose a new parameter that integrates both variables, named R-score. Next, we sought to evaluate the PPA for EGFR mutation calls between two independent NGS platforms using a subset of 40 samples from the same cohort. Remarkably, there was a significant linear correlation between the PPA and the R-score (r = 0.97; p < 0.001). Specifically, the PPA of samples with an R-score ≤ −1.25 was 95.83%, whereas PPA falls to 81.63% in samples with R-score ≤ 0.25. In conclusion, R-score significantly correlates with PPA and can assist laboratory medicine specialists and data scientists to select reliable variants detected by NGS.

scholarly journals Efficacy and Acquired Resistance of EGFR-TKI Combined with Chemotherapy as First-Line Treatment for Chinese Patients with Advanced Non-Small Cell Lung Cancer in a Real-world Setting

2020 ◽  
Author(s):  
Qianqian Wang ◽  
Wen Gao ◽  
Fangyan Gao ◽  
Shidai Jin ◽  
Tianyu Qu ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Advanced Nsclc ◽  
Acquired Resistance ◽  
Small Cell ◽  
Combination Group ◽  
Monotherapy Group ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Nsclc Patients ◽  
Egfr Tki

Abstract Background To compare the benefits and explore the cause of acquired resistance of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and its combination with chemotherapy in advanced non-small-cell lung cancer (NSCLC) patients harboring EGFR mutation in a real-life setting.Methods This retrospective analysis included 117 advanced NSCLC patients with EGFR mutation who underwent next-generation sequencing (NGS) prior to treatment. The combination group included 50 patients who received the regimen of EGFR-TKI combined with chemotherapy, while the EGFR-TKI monotherapy group included 67 patients treated with TKI only. The primary endpoint of this study was progression-free survival (PFS); the secondary endpoints were overall survival (OS), response rate, and toxicity.Results The median PFS was significantly longer in the combination group than in the EGFR-TKI monotherapy group (19.00 months [95% CI, 14.674-23.326] vs. 11.70 months [95% CI, 10.807-12.593], p = 0.000). Subgroup analysis showed a similar trend of results. The median OS was not reached in the combination group and was 38.50 (95% CI, 35.300-41.700) months in the EGFR-TKI monotherapy group (p = 0.586). Patients in the combination group were more likely to experience adverse events, most of which showed the severity of grade 1 or 2. T790M mutation remains the main reason for acquired resistance, and the frequency of T790M mutation was similar between the two groups (p = 0.898). Conclusions Compared with EGFR-TKI monotherapy, EGFR-TKI combined with chemotherapy significantly improved PFS in advanced NSCLC patients with EGFR mutation, with acceptable toxicity.

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