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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Debate on first-line treatment strategies in advanced non-small cell lung cancer with EGFR mutation: An expert panel meeting by the Italian Association of Thoracic Oncology (AIOT)

Lung Cancer, Journal Year: 2025, Volume and Issue: 201, P. 108100 - 108100

Published: Jan. 24, 2025

Language: Английский

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Osimertinib in the Treatment of Epidermal Growth Factor Receptor-Mutant Early and Locally Advanced Stages of Non-Small-Cell Lung Cancer: Current Evidence and Future Perspectives

Cancers, Journal Year: 2025, Volume and Issue: 17(4), P. 668 - 668

Published: Feb. 16, 2025

The treatment of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) patients was dramatically revolutionized by the introduction EGFR tyrosine kinase inhibitors in clinical practice, both advanced and locally advanced/early stages. present work focuses on osimertinib use early NSCLC Phase 3 trials have supported as new standard care, adjuvant setting disease. ADAURA study reported an overall survival (OS) advantage for completely resected stage II-IIIA EGFR-mutant tumors, while LAURA proved a statistically significant benefit progression-free (PFS) delay central nervous system metastasis development treated with maintenance after concurrent chemoradiotherapy In neoadjuvant setting, data osimertinib’s efficacy are conflicting; therefore, Neo-ADAURA is evaluating safety alone or combination chemotherapy II-IIIB common mutations. We discuss several issues that need to be clarified, such drug uncommon mutations, long-term impact survival, management resistance mechanisms. Moreover, we report studies trying identify potential biomarkers response, circulating tumor DNA (ctDNA), aim selecting who will most from osimertinib.

Language: Английский

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Furmonertinib in uncommon EGFR‐mutated non‐small cell lung cancer with central nervous system metastases: A retrospective cohort study

International Journal of Cancer, Journal Year: 2025, Volume and Issue: unknown

Published: April 29, 2025

Abstract Uncommon EGFR mutations constitute 10%–20% of all in non‐small cell lung cancer (NSCLC), forming a molecularly distinct and clinically heterogeneous subgroup. This retrospective cohort study evaluated the efficacy safety furmonertinib managing central nervous system (CNS) metastases among NSCLC patients with uncommon (excluding exon 20 insertion variants). Thirty‐one eligible treated at Affiliated Brain Hospital Nanjing Medical University between March 2022 August 2024 were enrolled. Serial cerebrospinal fluid (CSF) samples subjected to next‐generation sequencing for circulating tumor DNA (ctDNA) profiling. Clinical endpoints included CNS objective response rate (ORR), disease control (DCR), intracranial progression‐free survival (iPFS), overall (OS), parameters. The demonstrated ORR 38.7% (95% CI, 21.8%–57.8%) DCR 64.5% 45.4%–80.8%), median iPFS 6.97 months. Median OS remained immature data cutoff. A total 21 leptomeningeal had baseline EGFR‐mutant ctDNA detected their CSF, analysis indicating responses corresponded decreased or cleared abundance. Longitudinal CSF monitoring representative case significant temporal correlation molecular radiographic/clinical improvement. profile was favorable, no grade ≥4 adverse events treatment‐related mortality. These findings suggest that provides meaningful activity acceptable toxicity NSCLC, particularly when integrated dynamics as potential pharmacodynamic biomarker. highlights therapeutic implications third‐generation EGFR‐TKIs defined subpopulations.

Language: Английский

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Current management of uncommon EGFR mutations in non-small cell lung cancer

Current Problems in Cancer, Journal Year: 2024, Volume and Issue: 49, P. 101064 - 101064

Published: Feb. 3, 2024

Language: Английский

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