scholarly journals Patients with Exon 19 Deletion Were Associated with Longer Progression-Free Survival Compared to Those with L858R Mutation after First-Line EGFR-TKIs for Advanced Non-Small Cell Lung Cancer: A Meta-Analysis

PLoS ONE ◽  
2014 ◽  
Vol 9 (9) ◽  
pp. e107161 ◽  
Author(s):  
Yaxiong Zhang ◽  
Jin Sheng ◽  
Shiyang Kang ◽  
Wenfeng Fang ◽  
Yue Yan ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Free Survival ◽  
Exon 19 Deletion ◽  
L858r Mutation ◽  
Egfr Tkis ◽  
Exon 19

Efficacy of gefitinib in patients with advanced non-small cell carcinoma of the lung harboring common, uncommon and complex EGFR mutations

2021 ◽  
Vol 08 ◽  
Author(s):  
Wang Chun Kwok ◽  
Ka Yan Chiang ◽  
James Chung Man Ho ◽  
Terence Chi Chun Tam ◽  
Mary Sau Man Ip ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Small Cell ◽  
Egfr Mutations ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
Exon 19 Deletion ◽  
L858r Mutation ◽  
First Line Treatment ◽  
Exon 19

Background: As the commonest EGFR-TKI being used in Hong Kong, gefitinib has shown to be efficacious and safe as first line treatment for L858R mutation and exon 19 deletion with less gastrointestinal and cutaneous adverse events than erlotinib and afatinib. However, the evidence for therapeutic efficacy for uncommon and complex EGFR mutations is lacking. Whether gefitinib is efficacious for uncommon and complex EGFR mutations worth studying. Objectives: To assess the therapeutic efficacy of gefitinib, as measured by progression-free survival and overall survival, among advanced stage lung cancer patients with common, uncommon and complex EGFR mutations. Methods: This is a retrospective cohort study that included 241 Chinese patients with advanced non-small cell carcinoma of lung harboring EGFR mutations and received gefitinib 250 mg daily as first-line treatment. The progression-free survival [PFS] and overall survival [OS] for patients with different EGFR mutations, namely exon 19 deletion, L858R mutation in exon 21, uncommon EGFR mutations and complex EGFR mutations were analyzed. Results: Among the 241 patients, 118 [49%] had exon 19 deletion, 104 [43%] had L858R mutation in exon 21, 6 [2.5%] had uncommon EGFR mutations, 13 [5.4%] had complex EGFR mutations. The mean age was 69. 72% of the patients were female and with 81% being non-smoker. For patients with complex EGFR mutations, regardless of the presence of exon 19 deletion and L858R mutation as the component, have better PFS and OS than patients with single common EGFR mutations [Exon 19 deletion or L858R mutation]. Patients with uncommon EGFR mutations have inferior PFS and OS than those with common EGFR mutations. Conclusion: Gefitinib is a possible option for patients with complex EGFR mutations while it may not be the preferred treatment option in patients with single uncommon EGFR mutations.

scholarly journals The benefits and risks of pembrolizumab in combination with chemotherapy as first-line therapy in small-cell lung cancer: a single-arm meta-analysis of noncomparative clinical studies and randomized control trials

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qiangyun Liu ◽  
Yixuan Zhang ◽  
Miaowen Liu ◽  
Ruoxin Xu ◽  
Fengming Yi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Conventional Chemotherapy ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy

Abstract Background Although pembrolizumab has shown clinical benefit in patients with small-cell lung cancer (SCLC), its actual efficacy in combination with a conventional chemotherapy drug has not been determined. We performed this study to discern the efficacy and risk of pembrolizumab in combination with chemotherapy as first-line therapy in SCLC patients. Methods We systematically searched the PubMed, ScienceDirect, Cochrane Library, Scopus, Ovid MEDLINE, Embase, Web of Science, and Google Scholar databases for relevant studies. The main outcomes were overall survival (OS) and progression-free survival (PFS). Results We identified 2980 articles and included 6 studies (5 were noncomparative open-label studies and 1 was a randomized controlled trial [RCT]) involving 396 patients in our meta-analysis. The pooled median OS (mOS) was 9.6 months (95% CI, 8.0-11.2), and the pooled median PFS (mPFS) was 4.2 months (95% CI, 2.2-6.1). The 1-year overall survival rate (OSR-1y) and 6-month progression-free survival rate (PFSR-6m) were 45.1% (95% CI, 33-57.2%) and 41.6% (95% CI, 24.3-59%), respectively. The objective response rate (ORR) was 38.8% (95% CI, 11.9-65.67%), disease control rate (DCR) was 69.30% (95% CI, 51.6-87.0%), complete response (CR) was 2.20% (95% CI, 0.8-3.7%), partial response (PR) was 34.70% (95% CI, 7.8-61.5%), and stable disease (SD) was 20.90% (95% CI, 9.1-32.6%). The grade 3-4 adverse effect (AE) rate was 20.88% (95% CI, 1.22-54.85%). The most common AEs were neutropenia (90.16%), anemia (53.21%), dysphagia (41.96%), platelet count decrease (34.87%), and esophagitis (32.89%); severe AEs included neutropenia, respiratory failure, pneumonitis, acute coronary syndrome, and colitis/intestinal ischemia. Conclusions The combination of pembrolizumab with conventional chemotherapy is an effective therapeutic schedule with acceptable and manageable efficacy and toxicity in patients with SCLC. More high-quality and well-designed RCTs with large sample sizes are warranted to further validate our findings.

scholarly journals Rational Application of First-Line EGFR-TKIs Combined with Antiangiogenic Inhibitors in Advanced EGFR-Mutant Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Jie-Tao Ma ◽  
Yi-Jia Guo ◽  
Jun Song ◽  
Li Sun ◽  
Shu-Ling Zhang ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Meta Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Formula Group ◽  
Exon 19 Deletion ◽  
Egfr Mutant ◽  
Egfr Tki ◽  
Egfr Tkis

Purpose. A meta-analysis of randomized controlled trials (RCTs) was conducted to compare the difference in efficacy and safety between epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) with antiangiogenic inhibitors ( A + T ) and EGFR-TKI monotherapy in patients with treatment-naïve advanced EGFR-mutant non-small-cell lung cancer (NSCLC). Methods. PubMed, Embase, Web of Science, and Cochrane electronic databases were searched for relevant RCTs. Meeting abstracts were also reviewed to identify appropriate studies. The endpoints included progression-free survival (PFS), overall survival (OS), 1- and 2-year OS rates, objective response rate (ORR), and grade ≥ 3 adverse events. All pooled outcomes were expressed using hazard ratios (HRs) or relative risk ratios (RRs). Results. Data were collected from six eligible RCTs, which included 1,244 participants (619 in the A + T group and 625 in the TKI alone group). PFS was significantly improved with A + T compared to TKI alone ( HR = 0.60 ; P < 0.01 ) regardless of EGFR mutation types (exon 19 deletion or L858R) and brain metastasis status (with or without brain metastases). There was no significant difference in median OS between the A + T and TKI alone groups ( HR = 0.933 ; P = 0.551 ) regardless of EGFR mutation type. The ORR for A + T combination therapy was significantly increased compared to TKI monotherapy in exon 19 deletion subgroups ( RR = 0.774 ; P = 0.008 ). There was no difference in the positive rates of acquired T790M mutation between the two groups ( RR = 0.967 ; P = 0.846 ). More patients in the TKI alone group received a variety of subsequent systemic treatments than those in the A + T group ( RR = 0.881 ; P = 0.002 ). Conclusion. Addition of antiangiogenic inhibitors to first-line EGFR-TKI therapy significantly reduced the risk of disease progression for patients with advanced EGFR-mutant NSCLC regardless of EGFR mutation type and brain metastasis status. The lack of OS benefit may be explained by differences in subsequent treatments rather than drug resistance mechanisms.

Systematic review and network meta-analysis of first-line therapy for advanced EGFR-positive non-small-cell lung cancer

2019 ◽  
Vol 15 (24) ◽  
pp. 2857-2871 ◽  
Author(s):  
Jacob Franek ◽  
Joseph C Cappelleri ◽  
Kelly A Larkin-Kaiser ◽  
Keith D Wilner ◽  
Rickard Sandin
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Clinical Efficacy ◽  
Cell Lung Cancer ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Free Survival

Here, we compare the relative clinical efficacy of EGFR-targeted tyrosine kinase inhibitors ( EGFR TKIs) for EGFR-positive advanced non-small-cell lung cancer (NSCLC). The authors systematically searched 11 electronic databases from January 2004 to August 2018 for randomized controlled trials measuring clinical efficacy of first-line TKI therapies. Clinical efficacy outcomes included overall survival and progression-free survival. Bayesian network meta-analysis was used to assess the relative efficacy of first-line EGFR TKIs for overall survival and progression-free survival. This network meta-analysis showed that dacomitinib and osimertinib resulted in improved efficacy outcomes compared with afatinib, erlotinib and gefitinib. Both osimertinib and dacomitinib should be considered as standard first-line treatment options for patients diagnosed with advanced EGFR-positive non-small-cell lung cancer.

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 Prognostic value of the common tumour-infiltrating lymphocyte subtypes for patients with non-small cell lung cancer: A meta-analysis

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242173
Author(s):  
Benchao Chen ◽  
Heng Li ◽  
Chao Liu ◽  
Xudong Xiang ◽  
Shuting Wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Small Cell ◽  
High Density ◽  
Small Cell Lung ◽  
Free Survival ◽  
Tumour Nest ◽  
Disease Specific

Background Many previous studies have revealed that tumour-infiltrating lymphocytes (TILs) are significantly associated with prognosis in various tumours. However, this finding remains controversial in non-small cell lung cancer (NSCLC). We performed this meta-analysis systematically to evaluate the prognostic value of TILs in NSCLC. Methods The references were collected by searching the PubMed, EMBASE and Web of Science databases. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were summarized using random or fixed effects models to evaluate the association between TILs and NSCLC survival outcomes. Results A total of 45 interrelated studies were eligible that included 11,448 patients. Pooled analysis showed that a high density of TILs indicated a better overall survival (HR = 0.80, 0.70–0.89) and progression-free survival (HR = 0.73, 0.61–0.85) for patients with NSCLC; a high density of CD3+ TILs in the tumour nest indicated a better overall survival (HR = 0.84, 0.69–0.99) and disease-specific survival (HR = 0.57, 0.34–0.80); a high density of CD4+ TILs in the tumor nest indicated a favourable overall survival (HR = 0.86, 0.76–0.96); a high density of CD8+ TILs indicated a favourable overall survival (HR = 0.995, 0.99–1.0), progression-free survival (HR = 0.52, 0.34–0.71), disease-free survival (HR = 0.64, 0.43–0.85), relapse/recurrence-free survival (HR = 0.42, 0.18–0.67) and disease-specific survival (HR = 0.56, 0.35–0.78); and a high density of CD20+ TILs in the tumour nest indicated a favourable overall survival (HR = 0.65, 0.36–0.94). However, a high density of Foxp3+ TILs in the tumour stroma indicated a worse relapse/recurrence-free survival (HR = 1.90, 1.05–2.76) in NSCLC. Conclusions Our meta-analysis confirmed that high densities of TILs, CD3+TILs, CD4+TILs, CD8+TILs and CD20+TILs in the tumour nest are favourable prognostic biomarkers for patients with NSCLC, and Foxp3+TILs in the tumour stroma are a poor prognostic biomarker.

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