Genomic Alterations and the Incidence of Brain Metastases in Advanced and Metastatic NSCLC: A Systematic Review and Meta-Analysis

Gillespie, Conor S; Mustafa, Mohammad; Richardson, George E.; Alam, Ali M; Lee, Keng Siang; Hughes, David; Escriu, Carles; Zakaria, Rasheed

doi:10.1016/j.jtho.2023.06.017

Cited by 18 publications

(14 citation statements)

References 65 publications

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“…New-generation targeted therapies with blood barrier penetration increased the prognosis of brain metastatic NSCLC patients [ 58 ]. 20%–30% with advanced NSCLC were found to have BM at diagnosis [ 131 , 132 ]. Figure 5 shows the distribution of BM according to genetical alterations.…”

Section: Discussionmentioning

confidence: 99%

“…Figure 5 shows the distribution of BM according to genetical alterations. A recent meta-analysis suggests that patients with ALK-positive and EGFR-positive NSCLC had higher rates of BM development than other genomic alterations and wild-type tumors [ 131 ]. Others showed an association with metastasis development in tumors with ROS1, MET, and RET alterations [ 131 ].…”

Section: Discussionmentioning

confidence: 99%

“…A recent meta-analysis suggests that patients with ALK-positive and EGFR-positive NSCLC had higher rates of BM development than other genomic alterations and wild-type tumors [ 131 ]. Others showed an association with metastasis development in tumors with ROS1, MET, and RET alterations [ 131 ]. However, a meta-analysis does not support a higher rate of BM in these cases compared with wild-type cohorts [ 131 ].…”

Section: Discussionmentioning

confidence: 99%

“…Others showed an association with metastasis development in tumors with ROS1, MET, and RET alterations [ 131 ]. However, a meta-analysis does not support a higher rate of BM in these cases compared with wild-type cohorts [ 131 ]. BM are frequent in advanced EGFR-mutated or ALK-rearranged NSCLCs, with an estimated >45% of patients with CNS involvement by 3 years of survival with targeted therapies [ 133 ].…”

Section: Discussionmentioning

confidence: 99%

“… Frequency of oncogenic drivers for East-Asian and Western populations [ 134 ]. Bars are stratified according to proportions of brain metastases (BM) at diagnosis (blue) and BM development after diagnosis (orange) and pan-wild-type for all genetic alterations reported including rare ones (WT, green) [ 131 ]. For visual enhancement low frequencies of ALK, ROS1, RET genetical alterations are presented in a separate figure.…”

Section: Discussionmentioning

confidence: 99%

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Targeted therapeutic options in early and metastatic NSCLC-overview

Gálffy,

Morócz,

Korompay

et al. 2024

Pathol. Oncol. Res.

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The complex therapeutic strategy of non-small cell lung cancer (NSCLC) has changed significantly in recent years. Disease-free survival increased significantly with immunotherapy and chemotherapy registered in perioperative treatments, as well as adjuvant registered immunotherapy and targeted therapy (osimertinib) in case of EGFR mutation. In oncogenic-addictive metastatic NSCLC, primarily in adenocarcinoma, the range of targeted therapies is expanding, with which the expected overall survival increases significantly, measured in years. By 2021, the FDA and EMA have approved targeted agents to inhibit EGFR activating mutations, T790 M resistance mutation, BRAF V600E mutation, ALK, ROS1, NTRK and RET fusion. In 2022, the range of authorized target therapies was expanded. With therapies that inhibit KRASG12C, EGFR exon 20, HER2 and MET. Until now, there was no registered targeted therapy for the KRAS mutations, which affect 30% of adenocarcinomas. Thus, the greatest expectation surrounded the inhibition of the KRAS G12C mutation, which occurs in ∼15% of NSCLC, mainly in smokers and is characterized by a poor prognosis. Sotorasib and adagrasib are approved as second-line agents after at least one prior course of chemotherapy and/or immunotherapy. Adagrasib in first-line combination with pembrolizumab immunotherapy proved more beneficial, especially in patients with high expression of PD-L1. In EGFR exon 20 insertion mutation of lung adenocarcinoma, amivantanab was registered for progression after platinum-based chemotherapy. Lung adenocarcinoma carries an EGFR exon 20, HER2 insertion mutation in 2%, for which the first targeted therapy is trastuzumab deruxtecan, in patients already treated with platinum-based chemotherapy. Two orally administered selective c-MET inhibitors, capmatinib and tepotinib, were also approved after chemotherapy in adenocarcinoma carrying MET exon 14 skipping mutations of about 3%. Incorporating reflex testing with next-generation sequencing (NGS) expands personalized therapies by identifying guideline-recommended molecular alterations.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Targeted therapeutic options in early and metastatic NSCLC-overview

Gálffy,

Morócz,

Korompay

et al. 2024

Pathol. Oncol. Res.

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Integrated whole‐exome and bulk transcriptome sequencing delineates the dynamic evolution from preneoplasia to invasive lung adenocarcinoma featured with ground‐glass nodules

Zhou,

Li,

Liu

et al. 2024

Cancer Medicine

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ObjectiveThe genomic and molecular ecology involved in the stepwise continuum progression of lung adenocarcinoma (LUAD) from adenocarcinoma in situ (AIS) to minimally invasive adenocarcinoma (MIA) and subsequent invasive adenocarcinoma (IAC) remains unclear and requires further elucidation. We aimed to characterize gene mutations and expression landscapes, and explore the association between differentially expressed genes (DEGs) and significantly mutated genes (SMGs) during the dynamic evolution from AIS to IAC.MethodsThirty‐five patients with ground‐glass nodules (GGNs) lung adenocarcinomas were enrolled. Whole‐exome sequencing (WES) and transcriptome sequencing (RNA‐Seq) were conducted on all patients, encompassing both tumor samples and corresponding noncancerous tissues. Data obtained from WES and RNA‐Seq were subsequently analyzed.ResultsThe findings from WES delineated that the predominant mutations were observed in EGFR (49%) and ANKRD36C (17%). SMGs, including EGFR and RBM10, were associated with the dynamic evolution from AIS to IAC. Meanwhile, DEGs, including GPR143, CCR9, ADAMTS16, and others were associated with the entire process of invasive LUAD. We found that the signaling pathways related to cell migration and invasion were upregulated, and the signaling pathways of angiogenesis were downregulated across the pathological stages. Furthermore, we found that the messenger RNA (mRNA) levels of FAM83A, MAL2, DEPTOR, and others were significantly correlated with CNVs. Gene set enrichment analysis (GSEA) showed that heme metabolism and cholesterol homeostasis pathways were significantly upregulated in patients with EGFR/RBM10 co‐mutations, and these patients may have poorer overall survival than those with EGFR mutations. Based on the six calculation methods for the immune infiltration score, NK/CD8+ T cells decreased, and Treg/B cells increased with the progression of early LUAD.ConclusionsOur findings offer valuable insights into the unique genomic and molecular features of LUAD, facilitating the identification and advancement of precision medicine strategies targeting the invasive progression of LUAD from AIS to IAC.

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Immunotherapy for metastatic non–small cell lung cancer: Is it really a no‐brainer?

Young,

Halmos

2024

Cancer

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There is still much progress to be made in understanding the underlying mechanisms of brain metastasis development and its optimal therapy in non–small cell lung cancer (NSCLC); it is very important to expand research in this area because brain metastasis strongly affects patients' quality of life and overall survival. This editorial reviews the available data in the context of a recent meta‐analysis of the pivotal IMpower130, IMpower131, and IMpower150 studies, which explores metastatic epidermal growth factor receptor and anaplastic lymphoma kinase wild‐type NSCLC to determine potential preventative factors and risk factors for the development of brain metastasis, specifically the question of whether immunotherapy (the anti–programmed death ligand 1 antibody, atezolizumab in particular) plays a role in preventing brain metastasis.

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Genomic Alterations and the Incidence of Brain Metastases in Advanced and Metastatic NSCLC: A Systematic Review and Meta-Analysis

Cited by 18 publications

References 65 publications

Targeted therapeutic options in early and metastatic NSCLC-overview

Targeted therapeutic options in early and metastatic NSCLC-overview

Integrated whole‐exome and bulk transcriptome sequencing delineates the dynamic evolution from preneoplasia to invasive lung adenocarcinoma featured with ground‐glass nodules

Immunotherapy for metastatic non–small cell lung cancer: Is it really a no‐brainer?

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