EGFR-TKI Combined with Pemetrexed versus EGFR-TKI Monotherapy in Advanced EGFR-Mutated NSCLC: A Prospective, Randomized, Exploratory Study

Gu, Weiguang; Zhang, Hua; Lu, Yiyu; Li, Minjing; Yang, Shuang; Liang, Jing; Ye, Zhijian; Li, Zhihua; He, Minhong; Shi, Xiaoliang; Wang, Fei; You, Dong Gil; Gu, Weizhong; Feng, Weineng

doi:10.4143/crt.2022.1438

Cited by 5 publications

(5 citation statements)

References 34 publications

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“…The Kaplan-Meier methodology and the Cox proportional hazards model have been extensively used to analyze the OS and PFS across studies, comparing treatments such as camrelizumab with carboplatin and paclitaxel, brigatinib versus alectinib, and durvalumab with or without tremelimumab versus chemotherapy. These methods provide precise estimates of the survival time and assess the relative risks of events such as disease progression or death [46][47][48]62,67].…”

Section: Findings Of the Studiesmentioning

confidence: 99%

“…Regarding the blinding of participants and personnel (performance bias), many studies were evaluated as having a high risk due to the open nature of many clinical trials, which exposes them to possible performance bias. This includes the studies by Garon et [45,[47][48][49]51,52,54,62,64,66,69,70,[73][74][75][76][77][78][79]. The concern around unblinding in open clinical trials underscores a significant issue, as both the researchers and participants are aware of the assigned treatments, potentially influencing the outcomes and adherence to treatment.…”

Section: Risk Of Bias Assessmentmentioning

confidence: 99%

“…Conversely, studies with an unclear risk lacked detailed reporting, while a high risk indicated insufficient transparency, potentially undermining the study's validity. [45,[47][48][49]51,52,54,62,64,66,69,70,[73][74][75][76][77][78][79]. Allocation concealment (selection bias) was primarily rated as low risk, indicating that the allocation process was sufficiently concealed to reduce selection bias in most studies.…”

Section: Risk Of Bias Assessmentmentioning

confidence: 99%

“…al., 2021; Yang et al, 2023; G. Lo Russo et al, 2022; Garon et al, 2023; Si et al, 2021; Jiang et al, 2021; Zhang et al, 2024; Kim et al, 2022; Peters et al, 2022; Shi et al, 2022; Papadimitrakopoulou et al, 2020; Park et al, 2021; Gu et al, 2023; Zhong et al, 2023; Nomura et al, 2020; West et al, 2022; Lo Russo et al, 2023; Zhou et al, 2023; Sakai et al, 2020a; Redman et al, 2020; Hirsch et al, 2022; Schuler et al, 2020; Gadgeel et al, 2022; Ramalingam et al, 2022; Song et al, 2022; Anagnostou et al, 2023; and Park et al, 2020, were evaluated as having a low risk for random sequence generation (selection bias), suggesting thorough and well-documented randomization procedures[45,[47][48][49]51,52,54,62,64,66,69,70,[73][74][75][76][77][78][79].…”

mentioning

confidence: 99%

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Identification and Application of Emerging Biomarkers in Treatment of Non-Small-Cell Lung Cancer: Systematic Review

Restrepo,

Martínez Guevara,

Pareja López

et al. 2024

Cancers

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Non-small-cell lung cancer (NSCLC) comprises approximately 85% of all lung cancer cases, often diagnosed at advanced stages, which diminishes the effective treatment options and survival rates. This systematic review assesses the utility of emerging biomarkers—circulating tumor DNA (ctDNA), microRNAs (miRNAs), and the blood tumor mutational burden (bTMB)—enhanced by next-generation sequencing (NGS) to improve the diagnostic accuracy, prognostic evaluation, and treatment strategies in NSCLC. Analyzing data from 37 studies involving 10,332 patients from 2020 to 2024, the review highlights how biomarkers like ctDNA and PD-L1 expression critically inform the selection of personalized therapies, particularly beneficial in the advanced stages of NSCLC. These biomarkers are critical for prognostic assessments and in dynamically adapting treatment plans, where high PD-L1 expression and specific genetic mutations (e.g., ALK fusions, EGFR mutations) significantly guide the use of targeted therapies and immunotherapies. The findings recommend integrating these biomarkers into standardized clinical pathways to maximize their potential in enhancing the treatment precision, ultimately fostering significant advancements in oncology and improving patient outcomes and quality of life. This review substantiates the prognostic and predictive value of these biomarkers and emphasizes the need for ongoing innovation in biomarker research.

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Section: Findings Of the Studiesmentioning

confidence: 99%

Section: Risk Of Bias Assessmentmentioning

confidence: 99%

Section: Risk Of Bias Assessmentmentioning

confidence: 99%

mentioning

confidence: 99%

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Identification and Application of Emerging Biomarkers in Treatment of Non-Small-Cell Lung Cancer: Systematic Review

Restrepo,

Martínez Guevara,

Pareja López

et al. 2024

Cancers

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“…PEM is used in patients with LUAD who cannot receive targeted therapy due to its low toxicity and low adverse effects. Moreover, it is more suitable for older patients with poor general conditions and has shown advantages in second-line therapy after failure of EGFR-tyrosine kinase inhibitor treatment [ 7 , 8 ]. However, acquired resistance to PEM frequently occurs after use for approximately 2–5 months.…”

Section: Introductionmentioning

confidence: 99%

SP3-induced Timeless transcription contributes to cell growth of lung adenocarcinoma cells

Tian,

Du,

Yang

et al. 2024

PLoS ONE

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Background Timeless is well-known for its key role in replication checkpoints. Recent studies reveal the involvement of Timeless and specificity protein (SP) 1 in human malignancies. However, no evidence proved the interaction between SP3 and Timeless in lung adenocarcinoma (LUAD). Methods The expression and clinical significance of Timeless were analyzed using the LUAD dataset downloaded from the Cancer Genome Atlas (TCGA). Lentivirus-mediated Timeless knockdown in A549 cells was used to examine the role of Timeless in cell proliferation and pemetrexed (PEM) resistance. Transcription factors (TFs) bound to the Timeless promoter were identified by DNA pull-down technology with HPLC-MS/MS analysis and analyzed by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Dual-luciferase reporter assay was used to determine the activity of SP3 in Timeless transcription. Results Timeless was overexpressed in LUAD samples, and it could serve as a potential diagnostic or prognostic biomarker for LUAD patients. shTimeless-mediated knockdown of Timeless reduced cell viability and proliferation and sensitized PEM-resistant A549 cells to PEM. Four fragments (F1: 1–373 bp), (F2: 374–962 bp), (F4: 1274–1645 bp), and (F5: 1646-2000bp) were confirmed as the TF binding profiles of the Timeless promoter. KEGG analysis showed that the TFs bound to the Timeless promoter had relevance to spliceosome, RNA transport, and mRNA surveillance pathways. SP3 promoted the transcription of Timeless via the F2 fragment (374–962 bp) binding motif. Conclusion Upregulation of Timeless mediated by SP3 promotes LUAD cell proliferation, providing evidence to support that targeting the SP3/Timeless axis may be a potential therapeutic strategy against LUAD.

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Concomitant genomic features stratify prognosis to patients with advanced EGFR mutant lung cancer

Liang,

Xu,

Jiang

et al. 2024

Molecular Carcinogenesis

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This study aimed to explore the clinical significance of genomics features including tumor mutation burden (TMB) and copy number alteration (CNA) for advanced EGFR mutant lung cancer. We retrospectively identified 1378 patients with advanced EGFR mutant lung cancer and next‐generation sequencing tests from three cohorts. Multiple co‐occurring genomics alternations occurred in a large proportion (97%) of patients with advanced EGFR mutant lung cancers. Both TMB and CNA were predictive biomarkers for these patients. A joint analysis of TMB and CNA found that patients with high TMB and high CNA showed worse responses to EGFR‐TKIs and predicted worse outcomes. TMBhighCNAhigh, as a high‐risk genomic feature, showed predictive ability in most of the subgroups based on clinical characteristics. These patients had larger numbers of metastatic sites, and higher rates of EGFR copy number amplification, TP53 mutations, and cell‐cycle gene alterations, which showed more potential survival gain from combination treatment. Furthermore, a nomogram based on genomic features and clinical features was developed to distinguish prognosis. Genomic features could stratify prognosis and guide clinical treatment for patients with advanced EGFR mutant lung cancer.

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EGFR-TKI Combined with Pemetrexed versus EGFR-TKI Monotherapy in Advanced EGFR-Mutated NSCLC: A Prospective, Randomized, Exploratory Study

Abstract: We aimed to evaluate whether the addition of pemetrexed is effective in improving progression free survival in EGFR-mutated patients with or without concomitant alterations. Materials and Methods

Cited by 5 publications

References 34 publications

Identification and Application of Emerging Biomarkers in Treatment of Non-Small-Cell Lung Cancer: Systematic Review

Identification and Application of Emerging Biomarkers in Treatment of Non-Small-Cell Lung Cancer: Systematic Review

SP3-induced Timeless transcription contributes to cell growth of lung adenocarcinoma cells

Concomitant genomic features stratify prognosis to patients with advanced EGFR mutant lung cancer

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