scholarly journals Chinese Herbal Medicine Combined With First-Generation EGFR-TKIs in Treatment of Advanced Non-Small Cell Lung Cancer With EGFR Sensitizing Mutation: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yan Lu ◽  
Chenbing Sun ◽  
Lijing Jiao ◽  
Yu Liu ◽  
Yabin Gong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
First Generation ◽  
Advanced Nsclc ◽  
Meta Analysis ◽  
Acquired Resistance ◽  
Small Cell ◽  
Small Cell Lung ◽  
Chinese Herbal ◽  
Nsclc Patients ◽  
Egfr Tkis

Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. First-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) significantly improve prognosis of advanced NSCLC patients harboring EGFR sensitizing mutation. However, acquired resistance to EGFR-TKIs limits the good outcomes. Chinese herbal medicine (CHM) has been used for NSCLC patients receiving EGFR-TKIs for more than 10°years as an adjuvant treatment.Methods: Studies were searched from China BioMedical Literature, Chinese National Knowledge Infrastructure, Cqvip Database, Wanfang Database, MEDLINE (PubMed), EMBASE (Ovid), Google Scholar, and Cochrane Library from inception to March, 2021. Randomized controlled clinical trials (RCT) comparing EGFR-TKIs + CHM (TKIs + CHM) versus EGFR-TKIs with/without placebo (TKIs ± placebo) in participants with advanced NSCLC harboring EGFR sensitizing mutation were included in this study. Two authors screened all references, assessed the risk of bias and extracted data independently. Data were summarized using hazard ratio (HR) and risk ratios (RR), with 95% confidence intervals (CI) for binary outcomes. Meta-analysis was performed using random effects model. Overall quality of evidence was assessed using GRADE.Results: A total of 9 RCTs (1137 participants, 581 in the TKIs + CHM group and 556 in the TKIs ± placebo group) were included in this review. Only first-generation EGFR-TKIs were included. Most trials included used oral CHM preparations to tonify Qi and/or Yin. Treatment lasted from enrollment until disease progression (PD) or intolerable adverse events (AE). Combination of CHM with EGFR-TKIs improved median progression-free survival (mPFS) (HR,0.59; 95% CI, 0.52–0.68; P < 0.00001) and objective response rate (ORR) (RR, 1.23; 95% CI, 1.13–1.34; P < 0.00001) compared with used of EGFR-TKIs ± placebo. CHM reduced AE associated with EGFR-TKIs such as cutaneous toxicity (RR, 0.58; 95% CI, 0.46–0.73; P < 0.00001) and diarrhea (RR, 0.43; 95% CI, 0.30–0.60; P < 0.00001).Conclusion: Combination therapy of CHM and EGFR-TKIs significantly delays acquired resistance while improving ORR to EGFR-TKIs. Furthermore, CHM reduces AE induced by EGFR-TKIs. More international multi-centered, double-blinded, placebo-controlled, well-designed clinical trials are needed in future research.

ERK Inhibitor ASN007 Effectively Overcomes Acquired Resistance to EGFR Inhibitor in Non-small Cell Lung Cancer

2021 ◽  
Author(s):  
Bo Mi Ku ◽  
Jae Yeong Heo ◽  
Jinchul Kim ◽  
Jong-Mu Sun ◽  
Se-Hoon Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Acquired Resistance ◽  
Small Cell ◽  
Erk Signaling ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
Egfr Tki ◽  
Egfr Tkis

Abstract The emergence of acquired resistance limits the long-term efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs). Thus, development of effective strategies to overcome resistance to EGFR-TKI is urgently needed. Multiple mechanisms to reactivate ERK signaling have been successfully demonstrated in acquired resistance models. We found that in EGFR mutant non-small cell lung cancer (NSCLC) patients, acquired resistance to EGFR-TKIs was accompanied by increased activation of ERK. Increased ERK activation was also found in in vitro models of acquired EGFR-TKI resistance. ASN007 is a potent selective ERK1/2 inhibitor with promising antitumor activity in cancers with BRAF and RAS mutations. ASN007 treatment impeded tumor cell growth and the cell cycle in EGFR-TKI-resistant cells. In addition, combination treatment with ASN007 and EGFR-TKIs synergistically decreased the survival of resistant cells, enhanced induction of apoptosis, and effectively inhibited the growth of erlotinib-resistant xenografts, providing the preclinical rationale for testing combinations of ASN007 and EGFR-TKIs in EGFR-mutated NSCLC patients. This study emphasizes the importance of targeting ERK signaling in maintaining the long-term benefits of EGFR-TKIs by overcoming acquired resistance.

Chinese Herbal Medicine for Advanced Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

2018 ◽  
Vol 46 (05) ◽  
pp. 923-952 ◽  
Author(s):  
Xia-Wei Zhang ◽  
Wei Liu ◽  
Hong-Li Jiang ◽  
Bing Mao
Keyword(s):  
Lung Cancer ◽  
Survival Rate ◽  
Herbal Medicine ◽  
T Lymphocyte ◽  
Meta Analysis ◽  
Small Cell ◽  
Efficacy And Safety ◽  
Small Cell Lung ◽  
Chinese Herbal ◽  
Egfr Tkis

Chinese herbal medicine (CHM) has been widely used in the treatment of advanced non-small-cell lung cancer (NSCLC), but their efficacy and safety remain controversial. We sought to comprehensively aggregate and evaluate the available evidence on the efficacy and safety of the combination treatment with CHM and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in NSCLC patients. Our exhausted and systematical searching strategy yielded 64 related randomized controlled trials involving 4384 patients. Compared with EGFR-TKIs therapy alone, meta-analysis showed significant differences favoring the combination treatment in progression-free survival ([Formula: see text]), median survival time ([Formula: see text]), one-year survival rate ([Formula: see text]), two-year survival rate ([Formula: see text]), probability of severe toxicities ([Formula: see text]), objective response rate ([Formula: see text]), Karnofsky performance status ([Formula: see text]), and improvement in percentage of CD3[Formula: see text] T lymphocyte ([Formula: see text]) and CD4[Formula: see text] T lymphocyte ([Formula: see text]). Though these results require further confirmation, they are prone to show a potential therapeutic value of CHM in improving the clinical effect, overcoming the drug resistance and toxicities as an adjunctive therapy to EGFR-TKIs.

scholarly journals PD-(L)1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer Patients with High PD-L1 Expression: A Network Meta-Analysis

2021 ◽  
Vol 10 (7) ◽  
pp. 1365
Author(s):  
Margarita Majem ◽  
Manuel Cobo ◽  
Dolores Isla ◽  
Diego Marquez-Medina ◽  
Delvys Rodriguez-Abreu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Meta Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Potential Biomarker ◽  
Nsclc Patients

Programmed cell death-ligand 1 (PD-L1) has emerged as a potential biomarker for selection of patients more likely to respond to immunotherapy and as a prognostic factor in non-small cell lung cancer (NSCLC). In this network meta-analysis, we aimed to evaluate the efficacy of first-line anti-PD-(L)1 monotherapy in advanced NSCLC patients with high PD-L1 expression (≥50%) compared to platinum-based chemotherapy. We also evaluated efficacy outcomes according to tumor mutational burden (TMB). To that end, we conducted a systematic review. Six clinical trials with 2111 patients were included. In head-to-head comparisons, immunotherapy showed a significant improvement in progression-free survival (PFS: HRpooled = 0.69, 95% CI: 0.52–0.90, p = 0.007), overall survival (OS: HRpooled = 0.69, 95% CI: 0.61–0.78; p < 0.001) and overall response rate (ORR) (Risk ratio (RR)pooled = 1.354, 95% CI: 1.04–1.762, p = 0.024). In the assessment of relative efficacy for PFS through indirect comparisons, pembrolizumab (results from KEYNOTE-024) ranked highest followed by cemiplimab and atezolizumab, with statistical significance determined for some of the drugs. In terms of OS, cemiplimab ranked highest followed by atezolizumab and pembrolizumab, although non-significant OS was determined for these drugs. In conclusion, PD-(L)1 inhibitor monotherapy improves efficacy outcomes in the first line setting of advanced NSCLC patients with high PD-L1 expression. Evaluations with longer follow up are still needed to determine the superiority of any specific drug.

scholarly journals Prognostic value of TP53 concurrent mutations for EGFR- TKIs and ALK-TKIs based targeted therapy in advanced non-small cell lung cancer: a meta-analysis

2020 ◽  
Author(s):  
Kang Qin ◽  
Helei Hou ◽  
Yu Liang ◽  
Xiaochun Zhang
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Tp53 Mutation ◽  
Advanced Nsclc ◽  
Meta Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Tp53 Mutations ◽  
Egfr Tkis

Abstract Background The prognostic significance of TP53 concurrent mutations in patients with epidermal growth factor receptor (EGFR)- or anaplastic lymphoma kinase (ALK)- mutated advanced non–small-cell lung cancer (NSCLC) who received EGFR-tyrosine kinase inhibitors (TKIs) or ALK-TKIs based targeted therapy remains controversial. Therefore, the present meta-analysis was performed to investigate the association between TP53 concurrent mutations and prognosis of patients with advanced NSCLC undergoing EGFR-TKIs or ALK-TKIs treatments. Methods Eligible studies were identified by searching the online databases PubMed, Embase, Medline, The Cochrane library and Web of Science. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to clarify the correlation between TP53 mutation status and prognosis of patients. This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results In total, 15 studies with 1342 patients were included for final analysis. Overall, concurrent TP53 mutation was associated with unfavorable progression-free survival (PFS) (HR=1.88, 95%CI: 1.59-2.23, p<0.001, I2=0.0%, P=0.792) and overall survival (OS) (HR=1.92, 95%CI: 1.55-2.38, p<0.001, I2=0.0%, P=0.515). Subgroup analysis based on type of targeted therapy (EGFR-TKIs or ALK-TKIs, pathological type of cancer (adenocarcinoma only or all NSCLC subtypes) and line of treatment (first-line only or all lines) all showed that TP53 mutations was associated with shorter survivals of patients with EGFR-TKIs or ALK-TKIs treatments. Particularly, in patients with first-line EGFR-TKIs treatment, significantly poorer prognosis was observed in patients with TP53 concurrent mutations (pooled HR for PFS: 1.69, 95% CI 1.25-2.27, P<0.001, I2=0.0%, P=0.473; pooled HR for OS: 1.94, 95% CI 1.36-2.76, P<0.001, I2=0.0%, P=0.484). Begg’s funnel plots and Egger’s tests indicated no significant publication bias in this study. Conclusions This meta-analysis indicated that concurrent TP53 mutations was a negative prognostic factor and associated with poorer outcomes of patients with EGFR-TKIs or ALK-TKIs treatments in advanced NSCLC. In addition, our study provided evidence that TP53 mutations might be involved in primary resistance to EGFR-TKIs treatments in patients with sensitive EGFR mutations in advanced NSCLC.

scholarly journals Prognostic value of TP53 concurrent mutations for EGFR- TKIs and ALK-TKIs based targeted therapy in advanced non-small cell lung cancer: a meta-analysis

2020 ◽  
Author(s):  
Kang Qin ◽  
Helei Hou ◽  
Yu Liang ◽  
Xiaochun Zhang
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Tp53 Mutation ◽  
Advanced Nsclc ◽  
Meta Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Tp53 Mutations ◽  
Egfr Tkis

Abstract Background The prognostic significance of TP53 concurrent mutations in patients with epidermal growth factor receptor (EGFR)- or anaplastic lymphoma kinase (ALK)- mutated advanced non–small-cell lung cancer (NSCLC) who received EGFR-tyrosine kinase inhibitors (TKIs) or ALK-TKIs based targeted therapy remains controversial. Therefore, the present meta-analysis was performed to investigate the association between TP53 concurrent mutations and prognosis of patients with advanced NSCLC undergoing EGFR-TKIs or ALK-TKIs treatments. Methods Eligible studies were identified by searching the online databases PubMed, Embase, Medline, The Cochrane library and Web of Science. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to clarify the correlation between TP53 mutation status and prognosis of patients. This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results In total, 15 studies with 1342 patients were included for final analysis. Overall, concurrent TP53 mutation was associated with unfavorable progression-free survival (PFS) (HR=1.88, 95%CI: 1.59-2.23, p<0.001, I2=0.0%, P=0.792) and overall survival (OS) (HR=1.92, 95%CI: 1.55-2.38, p<0.001, I2=0.0%, P=0.515). Subgroup analysis based on type of targeted therapy (EGFR-TKIs or ALK-TKIs, pathological type of cancer (adenocarcinoma only or all NSCLC subtypes) and line of treatment (first-line only or all lines) all showed that TP53 mutations was associated with shorter survivals of patients with EGFR-TKIs or ALK-TKIs treatments. Particularly, in patients with first-line EGFR-TKIs treatment, significantly poorer prognosis was observed in patients with TP53 concurrent mutations (pooled HR for PFS: 1.69, 95% CI 1.25-2.27, P<0.001, I2=0.0%, P=0.473; pooled HR for OS: 1.94, 95% CI 1.36-2.76, P<0.001, I2=0.0%, P=0.484). Begg’s funnel plots and Egger’s tests indicated no significant publication bias in this study. Conclusions This meta-analysis indicated that concurrent TP53 mutations was a negative prognostic factor and associated with poorer outcomes of patients with EGFR-TKIs or ALK-TKIs treatments in advanced NSCLC. In addition, our study provided evidence that TP53 mutations might be involved in primary resistance to EGFR-TKIs treatments in patients with sensitive EGFR mutations in advanced NSCLC.

Radiotherapy with continued EGFR-TKIs for oligoprogressive disease in non-small cell lung cancer: A real-world study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20640-e20640
Author(s):  
Fang Wu ◽  
Sixuan Wu ◽  
Chunhong Hu
Keyword(s):  
Lung Cancer ◽  
Prognostic Factors ◽  
Advanced Nsclc ◽  
Cox Regression ◽  
Small Cell ◽  
Small Cell Lung ◽  
T790m Mutation ◽  
Nsclc Patients ◽  
Egfr Mutated ◽  
Egfr Tkis

e20640 Background: Almost all epidermal growth factor recept (EGFR)-mutated non-small-cell lung cancer (NSCLC) will develop tyrosine kinase inhibitors (TKIs) resistance. The treatment of oligoprogression is debatable after TKIs resistance. We conducted a real-world retrospective study to evaluate the efficacy of radiotherapy and continuation of TKIs in advanced NSCLC patients with oligoprogressive disease after EGFR-TKIs. Methods: From January 2011 to January 2019, we retrospectively analyzed EGFR-mutated NSCLC patients with oligoprogression in our institution. 33 patients were treated by radiotherapy and continuation of TKIs after oligoprogression. We used Kaplan-Meier and Cox regression model to analyse the prognostic factors of median progression-free survival (PFS) and median overall survival (OS) from the time of oligoprogression. Variables we selected for analyses included gender, age, smoking status, performance status (PS) score, stage at initial diagnosis, initial resectable, radiotherapy dose, EGFR mutation type, number of metastasis, sites of radiation, T790M status and the time of oligometastasis to radiotherapy. Results: 33 patients develop resistance to EGFR-TKIs at a median time of 11.0 months. The mPFS and mOS were 6.5 (95%CI, 1.4-11.6) and 21.8 (95%CI, 14.8-28.8) months, respectively. T790M mutation was tested in nine patients, four of which were mutation negative and five were positive. The mPFS was 15.5 (95%CI, 7.4-23.6) months in T790M mutation positive patients and 6.0 (95%CI, 0-14.0) months in negative patients. The mPFS in patients who started radiotherapy within or beyond 1 month after oligometastasis was 10.8 months (95% CI, 4.9-16.7 months) and 5.3 months (95% CI, 2.4-8.2 months). Cox regression model showed no variables significantly correlated with PFS difference. Univariate analysis identified female patients have longer OS (P = 0.038). The results of Multivariate analysis indicated that there was no OS-related prognostic factors. Conclusions: Radiotherapy with continued TKIs is an efficacious treatment option in advanced NSCLC patients with oligoprogressive disease after EGFR-TKIs. T790M mutation is a common mutation in NSCLC patients with oligoprogression. Gender was prognostic factors for OS. Moreover, there was a better prognosis in patients with T790M mutation positive or radiotherapy within 1 month after oligometastasis. However, this was not statistically significant. Larger sample size studies are needed to validate these clinical results.

scholarly journals ERK inhibitor ASN007 effectively overcomes acquired resistance to EGFR inhibitor in non‐small cell lung cancer

2022 ◽  
Author(s):  
Bo Mi Ku ◽  
Jae Yeong Heo ◽  
Jinchul Kim ◽  
Jong-Mu sun ◽  
Se-Hoon Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Acquired Resistance ◽  
Small Cell ◽  
Erk Signaling ◽  
Small Cell Lung ◽  
Nsclc Patients ◽  
Egfr Tki ◽  
Egfr Tkis

SummaryThe emergence of acquired resistance limits the long-term efficacy of EGFR tyrosine kinase inhibitors (EGFR TKIs). Thus, development of effective strategies to overcome resistance to EGFR TKI is urgently needed. Multiple mechanisms to reactivate ERK signaling have been successfully demonstrated in acquired resistance models. We found that in EGFR mutant non-small cell lung cancer (NSCLC) patients, acquired resistance to EGFR TKIs was accompanied by increased activation of ERK. Increased ERK activation was also found in in vitro models of acquired EGFR TKI resistance. ASN007 is a potent selective ERK1/2 inhibitor with promising antitumor activity in cancers with BRAF and RAS mutations. ASN007 treatment impeded tumor cell growth and the cell cycle in EGFR TKI-resistant cells. In addition, combination treatment with ASN007 and EGFR TKIs significantly decreased the survival of resistant cells, enhanced induction of apoptosis, and effectively inhibited the growth of erlotinib-resistant xenografts, providing the preclinical rationale for testing combinations of ASN007 and EGFR TKIs in EGFR-mutated NSCLC patients. This study emphasizes the importance of targeting ERK signaling in maintaining the long-term benefits of EGFR TKIs by overcoming acquired resistance.

scholarly journals Adjuvant EGFR-TKIs for Patients With Resected EGFR-Mutant Non-Small Cell Lung Cancer: A Meta-Analysis of 1,283 Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Rui-Lian Chen ◽  
Ling-Ling Sun ◽  
Yang Cao ◽  
Han-Rui Chen ◽  
Jing-Xu Zhou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Lower Risk ◽  
Meta Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Egfr Mutant ◽  
Nsclc Patients ◽  
Egfr Tkis

BackgroundCisplatin-based chemotherapy was previously considered as the standard adjuvant therapy for improved overall survival (OS) in patients with non-small cell lung cancer (NSCLC) after surgery. However, the benefit was limited due to high risks of recurrence and adverse events. In the present study, the efficacy of adjuvant epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for EGFR-mutant patients after surgery was investigated using the latest updated data.MethodsThis meta-analysis included a comprehensive range of relevant studies identified from database searches. Disease-free survival (DFS) and OS with hazard ratios (HRs) were calculated using random-effect or fixed-effect models. Subgroup analysis was also performed.ResultsA total of seven randomized clinical trials were included in the meta-analysis and involved 1,283 NSCLC patients harboring EGFR mutations. In resected EGFR-mutant NSCLC patients, adjuvant EGFR-TKIs were significantly better than chemotherapy in terms of DFS (HR: 0.41; 95%CI: 0.24–0.70, P = 0.001), without showing any benefit in OS (HR: 0.72; 95%CI: 0.37–1.41, P = 0.336). No significant difference in DFS was observed between patients with EGFR exon 19 deletion and those with L858R mutation. Resected EGFR-mutant NSCLC patients treated with osimertinib experienced improved DFS and a lower risk of brain recurrence than those treated with gefitinib or erlotinib. Adjuvant EGFR-TKIs reduced the risk of bone and lung relapse, without decreasing the risk of local recurrence and liver relapse.ConclusionThis meta-analysis shows that adjuvant EGFR-TKI therapy could significantly prolong DFS in patients with resected EGFR-mutant NSCLC. Treatment with osimertinib showed improved DFS with a lower risk of brain recurrence than treatment with gefitinib or erlotinib for resected disease.

scholarly journals Prognostic value of TP53 concurrent mutations for EGFR- TKIs and ALK-TKIs based targeted therapy in advanced non-small cell lung cancer: a meta-analysis

2019 ◽  
Author(s):  
Kang Qin ◽  
Helei Hou ◽  
Yu Liang ◽  
Xiaochun Zhang
Keyword(s):  
Lung Cancer ◽  
Targeted Therapy ◽  
Tp53 Mutation ◽  
Advanced Nsclc ◽  
Meta Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Tp53 Mutations ◽  
Egfr Tkis

Abstract Background The prognostic significance of TP53 concurrent mutations in patients with epidermal growth factor receptor (EGFR)- or anaplastic lymphoma kinase (ALK)- mutated advanced non–small-cell lung cancer (NSCLC) who received EGFR-tyrosine kinase inhibitors (TKIs) or ALK-TKIs based targeted therapy remains controversial. Therefore, the present meta-analysis was performed to investigate the association between TP53 concurrent mutations and prognosis of patients with advanced NSCLC undergoing EGFR-TKIs or ALK-TKIs treatments. Methods Eligible studies were identified by searching the online databases PubMed, Embase, Medline, The Cochrane library and Web of Science. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to clarify the correlation between TP53 mutation status and prognosis of patients. This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results In total, 15 studies with 1342 patients were included for final analysis. Overall, concurrent TP53 mutation was associated with unfavorable progression-free survival (PFS) (HR=1.88, 95%CI: 1.59-2.23, p<0.001, I2=0.0%, P=0.792) and overall survival (OS) (HR=1.92, 95%CI: 1.55-2.38, p<0.001, I2=0.0%, P=0.515). Subgroup analysis based on type of targeted therapy (EGFR-TKIs or ALK-TKIs, pathological type of cancer (adenocarcinoma only or all NSCLC subtypes) and line of treatment (first-line only or all lines) all showed that TP53 mutations was associated with shorter survivals of patients with EGFR-TKIs or ALK-TKIs treatments. Particularly, in patients with first-line EGFR-TKIs treatment, significantly poorer prognosis was observed in patients with TP53 concurrent mutations (pooled HR for PFS: 1.69, 95% CI 1.25-2.27, P<0.001, I2=0.0%, P=0.473; pooled HR for OS: 1.94, 95% CI 1.36-2.76, P<0.001, I2=0.0%, P=0.484). Begg’s funnel plots and Egger’s tests indicated no significant publication bias in this study. Conclusions This meta-analysis indicated that concurrent TP53 mutations was a negative prognostic factor and associated with poorer outcomes of patients with EGFR-TKIs or ALK-TKIs treatments in advanced NSCLC. In addition, our study provided evidence that TP53 mutations might be involved in primary resistance to EGFR-TKIs treatments in patients with sensitive EGFR mutations in advanced NSCLC.

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