scholarly journals Prognostic Value of BIM Deletion in EGFR-Mutant NSCLC Patients Treated with EGFR-TKIs: A Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Fangfang Lv ◽  
Liang Sun ◽  
Qiuping Yang ◽  
Zheng Pan ◽  
Yuhua Zhang
Keyword(s):  
Kinase Inhibitors ◽  
Meta Analysis ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Deletion Polymorphism ◽  
Asian Populations ◽  
Egfr Mutant ◽  
Nsclc Patients ◽  
Egfr Tkis

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.

Local ablative therapy (LAT) for oligoprogressive, EGFR-mutant, non-small cell lung cancer (NSCLC) after treatment with osimertinib.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20545-e20545 ◽  
Author(s):  
Chul Kim ◽  
Nitin Roper ◽  
Chuong D. Hoang ◽  
Eva Szabo ◽  
Maureen Connolly ◽  
...  
Keyword(s):  
Disease Progression ◽  
Kinase Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
T790m Mutation ◽  
Tki Treatment ◽  
Egfr Mutant ◽  
A Prospective Study ◽  
Egfr Tki ◽  
Egfr Tkis

e20545 Background: EGFR tyrosine kinase inhibitors (EGFR-TKIs) improve progression-free survival (PFS) in patients with EGFR-mutant NSCLC, but disease progression limits efficacy. Retrospective studies show a survival benefit to LAT in patients with oligoprogressive disease (progression at a limited number of anatomic sites). Methods: This is a prospective study of LAT in patients with oligoprogressive EGFR-mutant NSCLC. Patients with no prior EGFR-TKI therapy (cohort 1) or progression after 1st/2ndgeneration EGFR-TKIs with acquired T790M mutation (cohort 2) receive osimertinib. Upon progression, eligible patients with < = 5 progressing sites undergo LAT and resume osimertinib until disease progression. Patients previously treated with osimertinib qualifying for LAT upon disease progression are also eligible for treatment (cohort 3). Primary endpoint: evaluation of safety and efficacy of reinitiation of osimertinib after LAT (assessed by PFS). Additional goals are assessment of mechanisms of resistance to osimertinib by multi-omics analyses of tumor, blood, and saliva. Results: Between 04/2016 and 01/2017, 15 patients were enrolled (cohort 1: 9, cohort 2: 3, cohort 3: 3). Median age was 57 (range 36-71). Treatment was well tolerated. The most common adverse events (AEs) were rash, diarrhea, thrombocytopenia, and alanine transaminase elevation. Grade 3/4 AEs were observed in 4 (27%) patients. Among evaluable patients, objective response rates prior to LAT in cohorts 1 and 2 were 71% (5/7) and 100% (2/2), respectively, with 6.8 months median PFS (95% CI: 3.4 months-undefined) in cohort 1 and no progressions in cohort 2. To date, 5 patients (33%; cohort 1: 2; cohort 3: 3) had LAT. Two patients with 3 progressing sites underwent a combination of surgery and radiation. Three patients with 1 progressing site underwent surgery alone. Post-LAT PFS and results of molecular analyses will be presented. Conclusions: Patients with EGFR-mutant NSCLC and oligoprogression after EGFR-TKI therapy can be safely treated with LAT. In selected patients, this approach could potentially maximize duration of EGFR-TKI treatment and prevent premature switching to other systemic therapies. Clinical trial information: NCT02759835.

scholarly journals Predictors of Outcomes in Patients with EGFR-Mutated Non-Small Cell Lung Cancer Receiving EGFR Tyrosine Kinase Inhibitors: A Systematic Review and Meta-Analysis

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1259 ◽  
Author(s):  
Carlo Buonerba ◽  
Simona Iaccarino ◽  
Pasquale Dolce ◽  
Martina Pagliuca ◽  
Michela Izzo ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Egfr Mutation ◽  
Meta Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Exon 19 Deletion ◽  
L858r Mutation ◽  
Egfr Mutant ◽  
Nsclc Patients ◽  
Egfr Tkis

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.

scholarly journals Current Evidence of the Efficacy and Safety of Neoadjuvant EGFR-TKIs for Patients With Non-small Cell Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaoshun Shi ◽  
Xiaoying Dong ◽  
Jianxue Zhai ◽  
Xiguang Liu ◽  
Di Lu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Kinase Inhibitors ◽  
Meta Analysis ◽  
Objective Response ◽  
Current Evidence ◽  
Efficacy And Safety ◽  
Nsclc Patients ◽  
The Impact ◽  
Egfr Tki ◽  
Egfr Tkis

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.

scholarly journals Efficacy of Osimertinib in NSCLC Harboring Uncommon EGFR L861Q and Concurrent Mutations: Case Report and Literature Review

2021 ◽  
Vol 11 ◽  
Author(s):  
Ruiting Lin ◽  
Ruilian Chen ◽  
Zhiqiang Chen ◽  
Leihao Hu ◽  
Wei Guo ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Free Survival ◽  
First Line Therapy ◽  
Epidermal Growth ◽  
Good Treatment Option ◽  
Nsclc Patients ◽  
First And Second Generation ◽  
Egfr Tkis

The efficacy of first-and second-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in NSCLC patients with the EGFR L861Q mutation has been studied previously. However, there is little evidence on the efficacy of osimertinib in NSCLC patients with uncommon mutations. Here, we report the case of a 68-year-old man with advanced NSCLC with concurrent EGFR L861Q mutation as well as TP53 and RB1 mutations. The patient was treated with osimertinib as first-line therapy and achieved a remarkable progression-free survival of 15 months. His symptoms were significantly alleviated and the dose was well tolerated. The findings of the present study indicate that osimertinib might be a good treatment option for NSCLC patients with the L861Q mutation.

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 ◽  
...  
Keyword(s):  
Survival Data ◽  
Kinase Inhibitors ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Prognostic Parameter ◽  
Nsclc Patients ◽  
The Impact ◽  
Egfr Tkis

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.

scholarly journals The combination of fibrinogen concentrations and the platelet-to-lymphocyte ratio predicts survival in patients with advanced lung adenocarcinoma treated with EGFR-TKIs

2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110040
Author(s):  
Qiong He ◽  
Yamin Li ◽  
Xihong Zhou ◽  
Wen Zhou ◽  
Chunfang Xia ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Kinase Inhibitors ◽  
Characteristic Curve ◽  
Performance Status ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Platelet To Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Egfr Mutant ◽  
Egfr Tkis

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.

scholarly journals ERβ1 Expression Patterns Have Different Effects On EGFR TKIs Treatment Response in EGFR Mutant Lung Adenocarcinomas.

2020 ◽  
Author(s):  
Lijuan Zhang ◽  
Meng Tian ◽  
Jiamao Lin ◽  
Jianbo Zhang ◽  
Haiyong Wang ◽  
...  
Keyword(s):  
Western Blot ◽  
Cell Lines ◽  
Kinase Inhibitors ◽  
Expression Patterns ◽  
Estrogen Therapy ◽  
Growth Factor Receptor ◽  
Treatment Resistance ◽  
Progression Free Survival ◽  
Pathway Activation ◽  
Egfr Tkis

Abstract Background: Estrogen receptor β (ERβ) can regulate cellular signaling through non-genomic mechanisms, potentially promoting resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, the mechanisms underlying the ERβ-mediated resistance to EGFR TKIs remain poorly understood. Methods: qRT-PCR was performed to investigate ERβ1 and ERβ5 expression levels in cell lines. The localization of ERβ and ERβ1 within cells was assessed using immunocytochemistry and immunofluorescence. The effect of estradiol and/or gefitinib on EGFR signaling pathways was determined by western blot. Cell viability and colony formation assays were used to assess gefitinib response for different cell lines. The apoptosis was verified by tunel and western blot. Immunohistochemistry was used to assess the expression of ERβ1 in lung adenocarcinoma tissues. Patient survival was estimated using the Kaplan-Meier method, and comparisons between groups were conducted using log-rank tests. Results: PC9 cell lines stably overexpressing ERβ1 or ERβ1/ERβ5 were established successfully. Immunofluorescence revealed that ERβ5 overexpression partly retained ERβ1 in the cytoplasm. Immunoblotting analyses revealed that EGFR pathway activation levels were higher in PC9/ERβ1/5 cells than those in PC9/ERβ1 or control PC9 cells. In the presence of estradiol, PI3K/AKT/mTOR pathway activation levels were higher in ERβ1/5-expressing cells than those in ERβ1-expressing cells. Additionally, PC9/ERβ1/5 cells were less prone to the cytotoxic and pro-apoptotic effects of gefitinib compared with PC9/ERβ1 or control PC9 cells. Conclusion: Cytoplasmic ERβ1 was associated with poor progression-free survival in lung cancer patients treated with EGFR TKIs. These results suggest that anti-estrogen therapy might reverse EGFR TKI treatment resistance to some extent in selected patients.

Network meta-analysis (NMA) of immuno-oncology (IO) monotherapy as first-line (1L) treatments (txs) for advanced non-small cell lung cancer (NSCLC) with PD-L1 expression ≥50%.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21091-e21091
Author(s):  
Nicholas Freemantle ◽  
Yingxin Xu ◽  
Florence Wilson ◽  
Patricia Guyot ◽  
Chieh-I Chen ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Meta Analysis ◽  
Objective Response ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Sensitivity Analyses ◽  
Current Standard ◽  
Feasibility Assessment ◽  
Hazard Ratios ◽  
Nsclc Patients

e21091 Background: For advanced NSCLC patients (pts) with high (≥50%) PD-L1 expression, effective IO mono options with survival benefits are approved (pembrolizumab mono, current standard of care) and emerging (cemiplimab). In a recent Phase 3 trial, cemiplimab, a high-affinity, highly potent human PD-1 inhibitor approved for tx of advanced cutaneous squamous cell carcinoma, demonstrated significantly improved overall survival (OS) and progression-free survival (PFS) vs chemotherapy (CT) in advanced NSCLC pts with PD-L1 ≥50%. A systematic literature review and NMA were conducted to identify/compare the efficacy/safety from randomized controlled trials (RCTs) for cemiplimab vs pembrolizumab or other IO mono published 2010–19. Methods: Relevant RCTs were identified by searching Embase, MEDLINE, Cochrane, and conference proceedings with predefined search strategies according to ISPOR, NICE, and PRISMA guidelines. An NMA with time-varying hazard ratios (HRs) was performed for OS and PFS. Analyses were conducted for objective response rate (ORR), Grade (G) 3–5 all-cause adverse events (AE), G3–5 immune-mediated AE (IMAE) and discontinuation due to AEs (DAE). Fixed-effect models were used due to limited evidence. Results with standard constant HRs and various sensitivity analyses were conducted to account for differences in RCT designs and other txs. Results: The feasibility assessment determined that EMPOWER-Lung 1, KEYNOTE-024, and KEYNOTE-042 trials were eligible. IMpower110 was excluded since an incompatible PD-L1 assay (SP142) was used for pt selection. For 1L advanced NSCLC with PD-L1 ≥50%, cemiplimab was associated with significantly greater PFS and ORR, and comparable OS, G3–5 AEs, IMAEs, and all-cause DAEs vs pembrolizumab (Table). At 2 yrs, numerically more pts receiving cemiplimab vs pembrolizumab were alive (59% vs 49%) and significantly more were alive w/o progression (37% vs 18%). Conclusions: In advanced NSCLC pts with PD-L1 ≥50%, cemiplimab mono demonstrated significant improvements in PFS and ORR, and comparable OS, safety/tolerability vs pembrolizumab.[Table: see text]

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