Developments in predictive biomarker testing and targeted therapy in advanced stage non-small cell lung cancer and their application across European countries

The Lancet Regional Health - Europe, Journal Year: 2024, Volume and Issue: 38, P. 100838 - 100838

Published: March 1, 2024

In the past two decades, treatment of metastatic non-small cell lung cancer (NSCLC), has undergone significant changes due to introduction targeted therapies and immunotherapy. These advancements have led need for predictive molecular tests identify patients eligible therapy. This review provides an overview development current application biomarker testing in European with advanced stage NSCLC. Using data from eleven countries, we conclude that recommendations are incorporated national guidelines across Europe, although there differences their comprehensiveness. Moreover, availability recently EMA-approved varies between countries. Unfortunately, routine assessment national/regional rates is limited. As a result, it remains uncertain which proportion NSCLC Europe receive adequate testing. Lastly, Molecular Tumor Boards (MTBs) discussion test results widely implemented, but composition functioning lacking. The establishment MTB can provide framework interpreting rare or complex mutations, facilitating appropriate decision-making, ensuring quality control.

Language: Английский

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From Rarity to Reality: Osimertinib's Promising Horizon in Treating Uncommon EGFR Mutations in Non-Small Cell Lung Cancer

Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 30(15), P. 3128 - 3136

Published: May 20, 2024

In the realm of advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) therapy with tyrosine kinase inhibitors (TKI), addressing optimal treatment for uncommon EGFR mutations like G719X in exon 18, S768I 20, and L861Q 21 remains a pivotal yet challenging frontier. Contrary to well-established efficacy EGFR-TKIs common mutations, these alterations pose unmet medical needs due lack comprehensive evidence. While afatinib, second-generation EGFR-TKI, has received FDA approval patients was based on post-hoc analysis randomized clinical trials. Recent developments include multiple trials investigating both second- third-generation mutations. A noteworthy example is prospective phase II trial osimertinib including landmark UNICORN study, which shown promising results treating Despite various reports afatinib appropriate use TKIs unclear. This review aims consolidate findings from latest focused outlining variations therapeutic specific genetic mutation. By synthesizing findings, we aim guide oncologists toward more informed decisions employing NSCLC other than 20 insertion. Additionally, explore potential strategies tailored patient populations address challenges posed by

Language: Английский

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Roles of SPOCK1 in the Formation Mechanisms and Treatment of Non-Small-Cell Lung Cancer and Brain Metastases from Lung Cancer

OncoTargets and Therapy, Journal Year: 2025, Volume and Issue: Volume 18, P. 35 - 47

Published: Jan. 1, 2025

Lung cancer is a malignant tumor with high morbidity and mortality in China worldwide. Once it metastasizes to the brain, its prognosis very poor. Brain metastases are found about 20% of newly diagnosed non-small-cell lung (NSCLC) patients. About 30% NSCLC patients develop brain during treatment. that positive for EGFR, ALK, ROS1 variations especially likely metastasize brain. SPOCK1 proteoglycan systemic physiological functions. It regulates self-renewal metastasis-initiating cells, invasion metastasis from plays an important role progression treatment resistance, has higher expression metastatic tissues than other tissues. Current treatments include surgery, whole-brain radiotherapy, stereotactic targeted therapy, chemotherapy. involved many signaling pathways, by which influences variety methods. In this paper, progress research on reviewed guide decisions options clinical practice.

Language: Английский

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Research Trends of Tyrosine Kinase Inhibitors in EGFR-Mutated Non-Small Cell Lung Cancer: A Bibliometric Analysis

Drug Design Development and Therapy, Journal Year: 2025, Volume and Issue: Volume 19, P. 1703 - 1719

Published: March 1, 2025

Background: This study seeks to identify research trends and hotspots concerning tyrosine kinase inhibitors (TKIs) for the treatment of epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) through a comprehensive bibliometric analysis. Methods: Publications on TKIs EGFR-mutated NSCLC from 2006 2024 were analyzed using VOSviewer, CiteSpace, R-bibliometrix visualize collaboration, keyword co-occurrences, trends. Results: A total 962 articles analyzed, authored by 7,458 researchers 5,401 institutions across 208 countries. Wu Yi-Long was identified as most prolific author, contributing 30 publications. AstraZeneca emerged industrial leader with 103 articles, while New England Journal Medicine recognized primary journal highest link strength. Keyword co-occurrence analysis revealed significant topics including "gefitinib", "chemotherapy", "open label", "erlotinib." Moreover, burst indicated notable periods increased focus such "osimertinib" "liquid biopsy", suggesting emerging current in NSCLC. Conclusion: highlights NSCLC, emphasizing importance targeted therapies like gefitinib osimertinib future clinical practice enhancement. Keywords: inhibitors, cancer, bibliometrics, VOSviewer

Language: Английский

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Safety and Efficacy of Osimertinib in Patients With Non–Small-Cell Lung Cancer and Uncommon Tumoral Epidermal Growth Factor Receptor Mutations: A Systematic Review and Single-Arm Meta-Analysis

JCO Precision Oncology, Journal Year: 2024, Volume and Issue: 8

Published: Nov. 1, 2024

PURPOSE The activity of osimertinib is not fully characterized in non–small-cell lung cancer (NSCLC) with uncommon epidermal growth factor receptor ( EGFR ) mutations. Therefore, we conducted a systematic review and meta-analysis to assess the safety efficacy patients NSCLC harboring somatic METHODS PubMed, Embase, Cochrane Library were searched for eligible studies reporting mutations defined as any other than exon 19 deletion, L858R T790M mutations, 20 insertion, except when compound. Then, performed pool survival outcomes antitumoral activity, including intracranial (ic) response adverse events. RESULTS Fifteen comprising 594 included. most frequently observed solitary G719X 25% (81/327) L861Q 21% (69/327). common compound 12% (23/192) S768I 11% (22/192). Pooled analysis showed an objective rate (ORR) 51.30% (95% CI, 45.80 56.81), disease control (DCR) 90.11% 86.27 92.96), median progression-free 9.71 months 7.96 11.86), overall 16.79 9.93 28.39). icORR was 45.96% 30.18 62.17), icDCR 95.76% 69.84 100). Osimertinib well tolerated frequency grade 3 or more events 21.77% 6.24 43.33). CONCLUSION demonstrated robust without unanticipated concerns.

Language: Английский

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Rebiopsy Enhances Survival with Afatinib vs. Osimertinib in EGFR Exon 19 Deletion Non-Small Cell Lung Cancer: A Multicenter Study in Taiwan

Current Oncology, Journal Year: 2025, Volume and Issue: 32(1), P. 36 - 36

Published: Jan. 10, 2025

Afatinib and Osimertinib are first-line treatments for EGFR-mutated advanced non-small cell lung cancer (NSCLC), but their comparative efficacies the patient groups that benefit most remain unclear. This multicenter retrospective study evaluated efficacy of in NSCLC patients with EGFR 19del no brain metastases at diagnosis. The primary endpoints were time on treatment (ToT) overall survival (OS). Survival analyses performed three groups: followed by Osimertinib, other therapies, (alone or therapies). Rebiopsy practices, including T790M mutation detection, also analyzed disease progression Afatinib. Among 97 Afatinib-treated 60 Osimertinib-treated patients, showed a significantly longer ToT (23.3 vs. 16.5 months; p = 0.007). Median OS was numerically higher sequential (40.5 34.6 months Osimertinib; 0.473). demonstrated advantages, fewer upon adverse effects. In group, 64% underwent rebiopsy, 39% testing positive subsequently receiving Osimertinib. frequently parenchyma using non-surgical methods. this real-world study, achieved compared to metastases. use trend toward improved OS, highlighting importance rebiopsy identifying mutations guide subsequent therapy.

Language: Английский

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First-line treatment for advanced or metastatic EGFR mutation-positive non-squamous non-small cell lung cancer: a network meta-analysis

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 14

Published: Jan. 15, 2025

Several head-to-head meta-analyses have compared the efficacy and safety of different first-line treatments in patients with EGFR mutation-positive (M+) advanced or metastatic non-squamous non-small cell lung cancer (nsq-NSCLC). However, there is a lack comprehensive evaluation encompassing multiple treatment strategies. Our objective to conduct network meta-analysis that includes various modalities, enabling both direct indirect comparisons for more thorough assessment. We conducted search PubMed, Embase, Cochrane Library, Web Science databases from inception until May 8, 2024, identify eligible randomized controlled trials (RCTs). The primary endpoints were progression-free survival (PFS) overall (OS), while secondary outcomes included response rate (ORR) grade 3 higher adverse events (≥3AEs). Stata 15.0 R 4.3.2 software utilized meta-analysis. A total 30 RCTs, comprising 8654 participants, included. study encompassed following 19 treatments: Chemotherapy; Afatinib; Afatinib + Cetuximab; Apatinib Gefitinib; Befotertinib; Cetuximab Erlotinib; Erlotinib Bevacizumab; Gefitinib Olaparib; Icotinib; Icotinib Lazertinib; Naquotinib; Osimertinib; Osimertinib Chemotherapy. results indicated that, terms PFS, Chemotherapy (SUCRAs: 93.4%) 84.61%) most effective. Regarding OS, Lazertinib 89.72%), 72.07%), 70.74%) emerged as top three options. 92.27%) was associated best ORR improvement. For ≥3AEs, 74.93%) 69.42%) likely choices. Current evidence suggests considering safety, stands out preferred untreated M nsq-NSCLC. Notably, combination chemotherapy demonstrated superior benefits. due limitations number quality studies, these conclusions await further validation through high-quality research. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024562981, identifier CRD42024562981.

Language: Английский

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Rare exon 18 G719A and exon 21 L833V compound EGFR mutations show favorable response to Third-Generation TKI Furmonertinib: A case report and literature review

Investigational New Drugs, Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

Language: Английский

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Updates on the treatment of epidermal growth factor receptor‐mutant non–small cell lung cancer

Cancer, Journal Year: 2025, Volume and Issue: 131(S1)

Published: March 15, 2025

This review provides a comprehensive update on the evolving landscape of treatment for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations, particularly focusing advances in precision medicine and overcoming acquired resistance. Initial success first-generation EGFR tyrosine kinase inhibitors (TKIs) EGFR-mutated NSCLC has paved way oncology subsequent development third-generation TKIs, current standard care as first-line therapy advanced stage NSCLC. Furthermore, combinational approach TKI chemotherapy or amivantamab was associated prolonged progression-free survival. The role TKIs also been investigated locally early NSCLC, including perioperative neoadjuvant settings. However, most patients experience resistance, resistance mechanism is quite complex heterogeneous, highlighting importance tailored therapeutic approaches. Overall, this underscores dynamic treatment, emphasizing need personalized strategies to optimize patient outcomes.

Language: Английский

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Development of a lung immune prognostic index-based nomogram model for predicting overall survival and immune-related adverse events in non-small cell lung cancer patients treated with sintilimab

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: May 8, 2025

Background Sintilimab, a programmed cell death protein-1 (PD-1) inhibitor, has shown efficacy in non-small lung cancer (NSCLC), though response heterogeneity persists. Previous studies suggest that the Lung Immune Prognostic Index (LIPI) may predict prognosis and immune-related adverse events (irAEs) immunotherapy. This study aimed to develop validate LIPI-based nomograms for predicting overall survival (OS) irAEs NSCLC patients treated with sintilimab. Methods Multicenter data stratified 356 into training, internal validation, external validation cohorts. Propensity score matching (PSM) balanced baseline characteristics. Multivariable Cox regression identified OS predictors, were constructed using significant variables. Model performance was evaluated via concordance index (C-index), time-dependent receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA). Kaplan-Meier assessed risk stratification. Results Independent prognostic factors include clinical stage, treatment lines, LIPI scores albumin level. Among them, stage IV (hazard ratio [HR]=1.725, 95% confidence interval [CI] 1.529-1.902), line ≥2 (HR=1.302, 95%CI: 1.125-1.569), intermediate (HR=1.736, 1.586-1.925), poor (HR=1.568, CI: 1.361-1.637) level≥35 (HR=1.802, 1.698-2.023) OS. The prediction model demonstrated excellent discrimination across all cohorts, AUCs maintaining 0.770-0.850 1–2 year predictions. Consistent observed (C-index: training=0.778, validation=0.793, validation=0.790). For prediction, predictors included age, sex, Eastern Cooperative Oncology Group status (ECOG PS), scores. Similarly, showed robust (AUCs 0.754-0.835 predictions; C-index: training=0.805, validation=0.825, validation=0.775). Both significantly outperformed single-variable predictions analyses. DCA confirmed superior net benefit. Conclusion effectively predicted sintilimab-treated patients, offering valuable tools personalized decision-making.

Language: Английский

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