scholarly journals P76.53 Impact of Neutrophil-to-Lymphocyte Ratio in Patients with EGFR-Mutant NSCLC Treated with Tyrosine Kinase Inhibitors

2021 ◽  
Vol 16 (3) ◽  
pp. S610
Author(s):  
T. Ono ◽  
S. Igawa ◽  
K. Yamada ◽  
A. Kameda ◽  
A. Oguri ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Neutrophil To Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Egfr Mutant

Impact of neutrophil-to-lymphocyte ratio in patients with EGFR-mutant NSCLC treated with tyrosine kinase inhibitors

2020 ◽  
Vol 38 (3) ◽  
pp. 885-893 ◽  
Author(s):  
Taihei Ono ◽  
Satoshi Igawa ◽  
Shintaro Kurahayashi ◽  
Yuriko Okuma ◽  
Ai Sugimoto ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Neutrophil To Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Egfr Mutant

Prognostic value of neutrophil-to-lymphocyte ratio in advanced EGFR-mutated non-small cell lung cancer (NSCLC) treated with a tyrosine-kinase inhibitors: A retrospective analysis in a series of western patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23045-e23045
Author(s):  
Fausto Meriggi ◽  
Claudio Codignola ◽  
Giordano D. Beretta ◽  
Giovanni Luca Ceresoli ◽  
Alberto Caprioli ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Retrospective Analysis ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Neutrophil To Lymphocyte Ratio ◽  
Cox Regression Analysis ◽  
Lymphocyte Ratio ◽  
Significant Difference ◽  
The Absolute ◽  
Egfr Mutated

e23045 Background: Several studies demonstrated that an elevated neutrophil-to-lymphocyte ratio (NLR) correlate with a poor prognosis both in early and advanced stage of NSCLC. The aim of this retrospective analysis was to investigate the correlation between NLR and prognosis in caucasian patients diagnosed with advanced EGFR-mutated NSCLC and treated with tyrosine kinase inhibitors (TKIs). Methods: A retrospective database was used to identify consecutive patients diagnosed with advanced EGFR-mutated NSCLC and treated with TKIs. From January 2011 to December 2015, 63 patients from five Institutions were enclosed in our series. NLR was derived from the absolute neutrophil and the absolute lymphocyte counts of a full blood count.Survival curves were calculated with Kaplan-Meier method and data were compared by log-rank test. Prognostic significance of NLR were assessed using a Cox regression analysis. Results: Sixty-three eligible patients were stratified according to the mean pretreatment NLR value (3.57 ± 2.42). The chosen cut-off for NLR was 3.5. Forty patients had NLR < 3.5 while 23 patients had a value of NLR > 3.5.A statistical significant difference, both in PFS and OS, was found in the NLR < 3.5 group compared with the higher NLR group (PFS: p < 0.01, OS: p < 0.05). According to univariate analysis, histological type (adenocarcinoma vs non-adenocarcinoma) and NLR value correlate significantly with PFS and OS. In Cox multivariate analysis, only NLR ³ 3.5 resulted significantly associated as independent prognostic factor for worse PFS (HR 2.275, 95% CI 1.257-4.116, p < 0.01) and OS (HR 2.699, 95% CI 1.187-6.137, p < 0.05). Conclusions: Pre-treatment NLR seems to represent a reliable, simple, and easy to reproduce, laboratory tool to predict survival and outcome to therapies in western caucasian EGFR-mutated NSCLC patients. Further prospective trials are needed to definitively confirm its prognostic and predictive role.

scholarly journals Emerging Paradigms in the Development of Resistance to Tyrosine Kinase Inhibitors in Lung Cancer

2013 ◽  
Vol 31 (31) ◽  
pp. 3987-3996 ◽  
Author(s):  
Justin F. Gainor ◽  
Alice T. Shaw
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Genetic Alterations ◽  
Anaplastic Lymphoma ◽  
Development Of Resistance ◽  
Tki Resistance ◽  
Alk Positive ◽  
Egfr Mutant

The success of tyrosine kinase inhibitors (TKIs) in select patients with non–small-cell lung cancer (NSCLC) has transformed management of the disease, placing new emphasis on understanding the molecular characteristics of tumor specimens. It is now recognized that genetic alterations in the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) define two unique subtypes of NSCLC that are highly responsive to genotype-directed TKIs. Despite this initial sensitivity, however, the long-term effectiveness of such therapies is universally limited by the development of resistance. Identifying the mechanisms underlying this resistance is an area of intense, ongoing investigation. In this review, we provide an overview of recent experience in the field, focusing on results from preclinical resistance models and studies of patient-derived, TKI-resistant tumor specimens. Although diverse TKI resistance mechanisms have been identified within EGFR-mutant and ALK-positive patients, we highlight common principles of resistance shared between these groups. These include the development of secondary mutations in the kinase target, gene amplification of the primary oncogene, and upregulation of bypass signaling tracts. In EGFR-mutant and ALK-positive patients alike, acquired resistance may also be a dynamic and multifactorial process that may necessitate the use of treatment combinations. We believe that insights into the mechanisms of TKI resistance in patients with EGFR mutations or ALK rearrangements may inform the development of novel treatment strategies in NSCLC, which may also be generalizable to other kinase-driven malignancies.

Primary and secondary resistance mechanisms in first, second and third generation tyrosine kinase inhibitors in EGFR mutant non-small cell lung cancer patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21142-e21142
Author(s):  
Moushumi Suryavanshi ◽  
Sakshi Mattoo ◽  
Sanjeev Kumar Sharma ◽  
Anurag Mehta ◽  
Ullas Batra
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Primary Resistance ◽  
Secondary Resistance ◽  
Egfr Amplification ◽  
2Nd Generation ◽  
Met Amplification ◽  
Egfr Mutant ◽  
Exon 19

e21142 Background: Different molecular mechanisms of on target and off target primary and secondary resistance have been observed in EGFR mutant NSCLC patients after first(1st), second(2nd) and third (3rd) generation of tyrosine kinase inhibitors(TKIs). Next generation sequencing(NGS) offers a comprehensive method of detecting these mechanisms to decide next line of treatment. Methods: We retrospectively analyzed 430 samples of NSCLC for primary and secondary resistance to 1st, 2nd and 3rd TKIs. NGS was performed using thermofischer Ion Torrent Oncomine Focus 52 gene Assay. These cases were divided into 4 groups.1)Primary resistance to first and second generation TKIs 2)Primary resistance to 3rd generation TKI 3)Secondary resistance to 1st and 2nd generation TKI 4) Secondary resistance to 3rd generation TKI.Last group was further subgrouped into A when 3rd generation TKI was offered as second line after 1st or 2nd generation TKIs on detection of T790M and subgroup B when it was given as first line. Results: Group1 had 13 cases. There were 2 cases of complex EGFR exon 19 mutation p.Glu746_Leu747delinsValPro, 4 cases of EGFR exon 20 insertion, 1 case of dual EGFR L833V & H835L mutation, 2 cases with EGFR amplification with EGFR exon 19 del and PIK3CA C420_P421del along with EGFR exon 19 del. Four cases had no additional abnormality. Group 2 had 5 cases:1 case had L858R and E709A dual mutation, 2 cases had KRAS G13C and KRAS G12V along with EGFR exon 19 del. One case had EGFR amplification and one case had MET amplification along with EGFR exon 19 del respectively.Group 3 had 34 cases including 10 cases of EGFR L858R and 24 cases of exon 19 deletion.T790M mutation was detected in 8 patients, MET amplification in 7 cases,one case had both T790M and MET amplification. One case lost the primary EGFR exon 19 del. Others mutations detected were KRAS G13C, PIK3CA H1047R, TP53 R213Q and TP53 C242fs. Group3 had 15 cases with 7 cases in subgroup A and 9 cases in subgroup B. In subgroup A T790M mutation was lost in 6 out of 7 cases.One case which lost T790M developed ALK translocation.One case of EGFR exon 19 del retained EGFR T790M with EGFR C797S in cis allele. Other mutations detected were PIK3CA E542K and KRAS G12C. In subgroup B one case showed EGFR C797S(both cis and trans) besides the primary EGFR exon 19 del. One case showed BRAF G469A along with EGFR exon 19 del. Other mutations detected were CTNNB1 D32N, KRAS G12V, and PIK3CA E542K. Conclusions: Primary and secondary acquired resistance is unavoidable in EGFR mutant advanced NSCLC on any generation of TKIs. NGS offers an advantage in diagnosing mechanism of resistance for further choice of therapy.

Sign in / Sign up

Export Citation Format

Share Document