scholarly journals Neutrophil-Lymphocyte Ratio as a Prognostic Parameter in NSCLC Patients Receiving EGFR-TKIs: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Mingbo Tang ◽  
Xinliang Gao ◽  
He Sun ◽  
Suyan Tian ◽  
Junxue Dong ◽  
...  

Objective. To research the impact of neutrophil-lymphocyte ratio (NLR) as a prognostic parameter in non-small-cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Methods. We searched the databases such as the American Society of Clinical Oncology (ASCO), EMBASE, PubMed, the European Society of Medical Oncology (ESMO), Wanfang, and CNKI for articles illustrating the impact of pretreatment NLR on survival data in NSCLC patients undergoing EGFR-TKIs treatment. We did a meta-analysis for overall survival (OS) and progression-free survival (PFS). Results. We recruited 10 studies in our meta-analysis. Our study suggested that patients with low NLR had better PFS (hazard ratio (HR) = 1.67, 95% confidence interval (CI) = (1.16–2.39), and P value = 0.005) and OS (HR = 1.66, 95% CI = (1.08–2.55), and P value = 0.02) in comparison to patients with high NLR. Conclusion. In conclusion, our meta-analysis revealed that lower NLR predicted a better survival (PFS and OS) in patients receiving the treatment of EGFR-TKIs.

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Fangfang Lv ◽  
Liang Sun ◽  
Qiuping Yang ◽  
Zheng Pan ◽  
Yuhua Zhang

Background. Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is inevitable in EGFR-mutant non-small-cell lung cancer (NSCLC) patients. A germline 2903 bp deletion polymorphism of Bcl-2-like protein 11 (BIM) causes reduced expression of proapoptotic BH3-only BIM protein and blocks TKI-induced apoptosis of tumor cells. Yet the association between the deletion polymorphism and response to EGFR-TKI treatment remains inconsistent among clinical observations. Thus, we performed the present meta-analysis. Methods. Eligible studies were identified by searching PubMed, Embase, and ClinicalTrials.gov databases prior to March 31, 2021. Hazard ratios (HRs) and 95% confidence intervals (CIs) of progression-free survival (PFS) and overall survival (OS) and odds ratios (ORs) and 95% CIs of objective response rate (ORR) and disease control rate (DCR) were calculated by using a random effects model. Sensitivity, metaregression, and publication bias analyses were also performed. Results. A total of 20 datasets (3003 EGFR-mutant NSCLC patients receiving EGFR-TKIs from 18 studies) were included. There were 475 (15.8%) patients having the 2903-bp intron deletion of BIM and 2528 (84.2%) wild-type patients. BIM deletion predicted significantly shorter PFS ( HR = 1.35 , 95% CI: 1.10-1.64, P = 0.003 ) and a tendency toward an unfavorable OS ( HR = 1.22 , 95% CI: 0.99-1.50, P = 0.068 ). Patients with deletion polymorphism had lower ORR ( OR = 0.60 , 95% CI: 0.42-0.85, P = 0.004 ) and DCR ( OR = 0.59 , 95% CI: 0.38-0.90, P = 0.014 ) compared with those without deletion. Conclusion. BIM deletion polymorphism may confer resistance to EGFR-TKIs and can be used as a biomarker to predict treatment response to EGFR-TKIs in EGFR-mutant NSCLC patients from Asian populations.


2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaoshun Shi ◽  
Xiaoying Dong ◽  
Jianxue Zhai ◽  
Xiguang Liu ◽  
Di Lu ◽  
...  

PurposeEpidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been indicated to be an effective treatment for advanced EGFR-mutant NSCLC. However, the neoadjuvant application of EGFR-TKIs in resectable NSCLC needs further investigation. Here, we aimed to evaluate the efficacy and safety of neoadjuvant EGFR-TKIs for lung cancer.MethodsPublished studies on neoadjuvant EGFR-TKIs in NSCLC were identified in PubMed, Web of Science, and EMBASE until June 1, 2020. Data on surgical rates, objective response rates (ORRs), pathologic responses, and adverse event (AE) rates were retrieved for proportional meta-analysis.ResultsIn total, 7 enrolled studies involving 129 EGFR-TKI-sensitive NSCLC patients were included in this analysis. The overall surgical rate in these studies was 95% (95% CI: 83% to 100%), with an ORR of 48% (95% CI: 39% to 57%) in the population with EGFR-TKI-sensitive mutations, whereas the ORR including wild-type EGFR patients was 28% (95% CI: 14% to 44%). The rate of grade 1-2 AEs was 69% (95% CI: 41% to 91%) but with an acceptable rate of grade 3-4 AEs of 0% (95% CI: 0% to 5%). The pooled rates of rash and diarrhea were 56% (95% CI: 31% to 79%) and 25% (95% CI: 6% to 51%), respectively. The impact of neoadjuvant EGFR-TKIs on survival remains inconclusive.ConclusionsNeoadjuvant EGFR-TKIs showed objective responses in approximately half of EGFR-sensitive NSCLC patients with a tolerable adverse effect profile. The favorable impact of neoadjuvant EGFR-TKIs on NSCLC needs more evidence for validation, such as the comparison of survival improvement between EGFR-TKIs and chemotherapy. The efficacy of neoadjuvant next-generation EGFR-TKIs in clinical trials remains unclear.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Rongqiang Liu ◽  
Shiyang Zheng ◽  
Qing Yuan ◽  
Peiwen Zhu ◽  
Biao Li ◽  
...  

Purpose. The prognostic value of a new scoring system, termed F-NLR, that combines pretreatment fibrinogen level with neutrophil-lymphocyte ratio has been evaluated in various cancers. However, the results are controversial. The purpose of this study was to comprehensively analyze the prognostic value of F-NLR score in patients with cancers. Methods. An integrated search of relevant studies was conducted by screening the PubMed and Embase databases. Pooled hazard ratios, with 95% confidence intervals (CIs), for overall survival (OS) and disease-free survival (DFS)/progression-free survival (PFS) were calculated to estimate the prognostic significance of F-NLR score in patients with various tumors. A random effects model was used for comprehensive analysis, and subgroup and meta-regression analyses were used to explore sources of heterogeneity. Results. Thirteen articles reporting data from of 4747 patients were included in the study. Pooled analysis revealed that high F-NLR score was significantly associated with poor OS ( HR = 1.77 ; 95% CI, 1.51–2.08) and poor DFS/PFS ( HR = 1.63 ; 95% CI, 1.30–2.05). Subgroup and meta-regression analyses did not alter the prognostic role of F-NLR score in OS and DFS/PFS. Conclusions. Increased F-NLR score is significantly associated with poor prognosis in patients with cancers and can serve as an effective prognostic indicator.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
R.-D. Hofheinz ◽  
U. Ronellenfitsch ◽  
S. Kubicka ◽  
A. Falcone ◽  
I. Burkholder ◽  
...  

Background. In metastatic colorectal cancer (mCRC), continuing antiangiogenic drugs beyond progression might provide clinical benefit. We synthesized the available evidence in a meta-analysis.Patients and Methods. We conducted a meta-analysis of studies investigating the use of antiangiogenic drugs beyond progression. Eligible studies were randomized phase II/III trials. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoints were the impact of continuing antiangiogenic drugs (i) in subgroups, (ii) in different types of compounds targeting the VEGF-axis (monoclonal antibodies versus tyrosine kinase inhibitors), and (iii) on remission rates and prevention of progression.Results. Eight studies (3,668 patients) were included. Continuing antiangiogenic treatment beyond progression significantly improved PFS (HR 0.64; 95%-CI, 0.55–0.75) and OS (HR 0.83; 95%-CI, 0.76–0.89). PFS was significantly improved in all subgroups with comparable HR. OS was improved in all subgroups stratified by age, gender, and ECOG status. The rate of patients achieving at least stable disease was improved with an OR of 2.25 (95%-CI, 1.41–3.58).Conclusions. This analysis shows a significant PFS and OS benefit as well as a benefit regarding disease stabilization when using antiangiogenic drugs beyond progression in mCRC. Future studies should focus on the optimal sequence of administering antiangiogenic drugs.


2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110040
Author(s):  
Qiong He ◽  
Yamin Li ◽  
Xihong Zhou ◽  
Wen Zhou ◽  
Chunfang Xia ◽  
...  

Objective This study aimed to identify a predictive marker of response to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in patients with EGFR-mutant advanced lung adenocarcinoma. Methods A cohort of 190 patients with EGFR-mutant advanced lung adenocarcinoma was analyzed. Receiver operating characteristic curve analysis was used to evaluate the optimal cutoffs for fibrinogen levels, the neutrophil-to-lymphocyte ratio (NLR), and the platelet-to-lymphocyte ratio (PLR) for predicting progression-free survival (PFS). Univariate and multivariate survival analyses were performed to identify factors correlated with PFS and overall survival (OS). Results High NLR was associated with worse performance status. In univariate analysis, fibrinogen levels, NLR, and PLR were correlated with OS and PFS. In multivariate analysis, all three variables remained predictive of OS, whereas only fibrinogen levels and PLR were independent prognostic factors for PFS. Furthermore, the combination of fibrinogen levels and PLR (F-PLR score) could stratify patients into three groups with significantly different prognoses, and the score was independently predictive of survival. Conclusion The F-PLR score predicted the prognosis of patients with EGFR-mutant advanced lung adenocarcinoma who received EGFR-TKIs, and this score may serve as a convenient blood-based marker for identifying high-risk patients.


2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 534-534 ◽  
Author(s):  
David Chan ◽  
Eva Segelov ◽  
Jeremy David Shapiro ◽  
Timothy Jay Price ◽  
Christos Stelios Karapetis ◽  
...  

534 Background: Biologic therapies used in treatment of mCRC are expensive and there is debate about their value. We examined the impact of biologic therapy on overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade 3/4 toxicity for patients beyond first-line treatment. Methods: MEDLINE, EMBASE, and Cochrane libraries were searched for randomized studies in relapsed mCRC comparing treatment containing targeted therapy to the same treatment without targeted therapy. Biologic agents were classed as: EGFR-inhibitors (EGFR-I), VEGF antibody/trap and VEGFR tyrosine kinase inhibitors (TKI). Only KRAS wild-type patients were included for EGFR-I analysis. Results were aggregated according to standard meta-analytic techniques. Results: 10 studies evaluating 5,847 patients were identified. Considering subgroups and lines, OS and PFS benefit was demonstrated in all groups across all lines except for OS in 2nd line EGFR-I use (which may be due to subsequent crossover). A benefit to ORR was seen with EGFR-I 2nd line (Pooled ORR benefit +24%, Odds Ratio (OR) 4.44, 95% CI 3.20-6.18), EGFR-I 3rd line and beyond (Pooled ORR benefit +16%), VEGF antibody/trap (Pooled ORR benefit +7.2%, OR 2.00, 95% CI 1.57-2.54) and VEGFR TKI (Pooled ORR benefit +1.9%, OR 2.05, 95% CI 1.27-3.30). The risk of grade 3/4 toxicity was greater with the addition of all targeted agents. Conclusions: The use of VEGF and EGFR targeted biologic agents beyond first-line setting in mCRC results in a benefit to OS, PFS and ORR for all agents except for OS benefit with second-line EGFR-I. This benefit comes at the cost of increased toxicity. [Table: see text]


Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1259 ◽  
Author(s):  
Carlo Buonerba ◽  
Simona Iaccarino ◽  
Pasquale Dolce ◽  
Martina Pagliuca ◽  
Michela Izzo ◽  
...  

Some commonly available patient or disease characteristics may be associated with progression-free survival (PFS) and overall survival (OS) in EGFR-mutant non-small cell lung cancer (NSCLC) patients receiving EGFR-TKIs (epidermal growth factor receptor - tyrosine kinase inhibitors). We performed a systematic review and meta-analysis of randomized control trials (RCTs) to explore differences in outcomes associated with EGFR-TKIs among subgroups of EGFR-mutant NSCLC patients. Pooled HRs for progression or death (PFS-HRs) and pooled HRs for death (OS-HRs) were compared among sub-groups defined according to baseline clinical and demographic variables as well as type of EGFR mutation. In the entire assessable population of 4465 EGFR-mutant NSCLC patients, significant interactions with PFS were found for gender (males vs. females; pooled ratio of the PFS-HRs = 1.2; 95% CI 1.12–1.56), smoking history (smokers vs. non-smokers; pooled ratio of the PFS-HRs = 1.26; 95% CI 1.05–1.51), and type of EGFR mutation (patients with exon 21 L858R mutation vs. exon 19 deletion; pooled ratio of the PFS-HRs = 1.39; 95% CI 1.18–1.63). Male patients, smokers and patients with EGFR exon 21 L858R mutation may derive less benefit from EGFR-TKIs compared to female patients, non-smokers and patients with EGFR exon 19 deletion.


2021 ◽  
Vol 20 ◽  
pp. 153303382110334
Author(s):  
Hua Chen ◽  
Ke-dong Han ◽  
Zhi-jiang He ◽  
Yi-sheng Huang

Background: The development of immunotherapy has dramatically changed the treatment of non-small-cell lung cancer. The negative association of antibiotics on the clinical activity of immune checkpoint inhibitors in patients with NSCLC is well known. Methods: PubMed, Embase, and Medline databases were searched until January 11, 2020. We included retrospective studies of ICIs (e.g., PD-1, PD-L1, and CTLA-4). The clinical outcomes were progression-free survival (PFS) and overall survival (OS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated, and subgroup and sensitivity analyses were performed. Results: Our results indicated that the use of antibiotics reduced the survival of NSCLC patients treated with ICIs. The pooled HRs of PFS and OS were HR = 1.41 (95% CI = 1.23-1.61; P < 0.001) and HR = 2.16 (95% CI = 1.79-2.60; P < 0.001). We divided the studies into 5 subgroups according to antibiotic exposure time. Subgroup analysis showed that the patients that were administered antibiotics [−60 days; 0 days] or [−30 days; 0 days] before the initiation of ICIs treatment had a poorer OS rate, whereas those patients that were administered antibiotics [0 days; 30 days] after the initiation of ICIs treatment had a poorer PFS rate. In summary, ATB treatment in patients [−60 days; +30 days] near the initiation of ICIs treatment significantly reduced the survival in NSCLC patients. Conclusion: Our results indicated that ATB use is negatively associated with survival in NSCLC patients treated with ICIs immunotherapy. Similar studies involving a larger sample of cases are still being published. This meta-analysis identified that the timing of ATB treatment in NSCLC patients receiving ICIs immunotherapy has different effects on the OS and PFS of these patients. ATB treatment prior to the initiation of ICIs treatment affects OS, whereas ATB treatment after the initiation of ICIs treatment affects PFS.


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