Oncogenic alterations in advanced NSCLC: a molecular super-highway

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Feb. 12, 2024

Lung cancer ranks among the most common cancers world-wide and is first cancer-related cause of death. The classification lung has evolved tremendously over past two decades. Today, non-small cell (NSCLC), particularly adenocarcinoma, comprises a multitude molecular oncogenic subsets that change both prognosis management disease.Since targeted alteration identified in 2004, with epidermal growth factor receptor (EGFR), there been unprecedented progress identifying targeting new alterations. Almost decades experience have allowed scientists to elucidate biological function drivers understand often overcome basis acquired resistance mechanisms. targetable alterations are approximately 60% adenocarcinoma patients Western populations 80% Asian populations. Oncogenic largely enriched non-smokers, east Asians, younger patients, though each its own patient phenotype.The current landscape druggable targets includes EGFR, anaplastic lymphoma kinase (ALK), v-raf murine sarcoma viral oncogene homolog B (BRAF), ROS proto-oncogene 1 (ROS1), Kirstin rat virus (KRAS), human 2 (HER2), c-MET (MET), neurotrophic tyrosine (NTRK), rearranged during transfection (RET), neuregulin (NRG1). In addition these known targets, others including Phosphoinositide 3-kinases (PI3K) fibroblast (FGFR) garnered significant attention subject numerous ongoing trials.In this era personalized, precision medicine, it paramount importance identify or potential patient. development therapy mirrored by diagnostic progress. Next generation sequencing offers high-throughput, speed breadth entire genomes regions DNA RNA. It for identification majority unique window into novel alterations, de novo mechanisms.In review, we discuss approach advanced NSCLC, focusing on driver through their pathophysiology, management, future perspectives. We also explore shortcomings hurdles encountered rapidly evolving field.

Language: Английский

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Unveiling the Landscape of Uncommon EGFR Mutations in NSCLC-A Systematic Review

Journal of Thoracic Oncology, Journal Year: 2024, Volume and Issue: 19(7), P. 973 - 983

Published: March 16, 2024

Language: Английский

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The study of primary and acquired resistance to first-line osimertinib to improve the outcome of EGFR-mutated advanced Non-small cell lung cancer patients: the challenge is open for new therapeutic strategies

Critical Reviews in Oncology/Hematology, Journal Year: 2024, Volume and Issue: 196, P. 104295 - 104295

Published: Feb. 20, 2024

The development of targeted therapy in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients has radically changed their clinical perspectives. Current first-line standard treatment for advanced disease is commonly considered third-generation tyrosine kinase inhibitors (TKI), osimertinib. study primary and acquired resistance to front-line osimertinib one the main burning issues further improve patients' outcome. Great heterogeneity been depicted terms duration benefit pattern progression this might be related molecular factors including subtypes EGFR mutations concomitant genetic alterations. Acquired can categorized into two classes: EGFR-dependent EGFR-independent mechanisms specific have demonstrated. purpose manuscript provide a comprehensive overview literature about osimertinib, from perspective therefore relationship emerging therapeutic approaches.

Language: Английский

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Uncommon EGFR Compound Mutations in Non-Small Cell Lung Cancer (NSCLC): A Systematic Review of Available Evidence

Current Oncology, Journal Year: 2022, Volume and Issue: 29(1), P. 255 - 266

Published: Jan. 9, 2022

Compound epidermal growth factor receptor (EGFR) mutations represent a heterogeneous subgroup of non-small cell lung cancer (NSCLC) patients with uncommon EGFR mutations. We conducted systematic review to investigate the available data on this patients’ subgroup. Overall, we found high heterogeneity in incidence compound (4–26% total mutant cases), which is dependent different testing methods adopted and specific considered. In addition, relative distinct subclasses identified reported extreme variability studies. Preclinical clinical data, excluding de novoEGFR exon 20 p.T790M mutations, show good responses tyrosine kinase inhibitors (TKIs) (combined common mutations: response rate (RR) ≥ 75% either first- or second-generation TKIs; combined plus uncommon: RR 40–80% 100% first-generation TKIs afatinib, respectively; 20–70%, ~80% ~75% TKIs, afatinib osimertinib, respectively). are consistent supporting use treating taking into account sensitivity profile accompanying for selecting most adequate TKI individual patients.

Language: Английский

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First-Line Osimertinib for Previously Untreated Patients With NSCLC and Uncommon EGFR Mutations

JAMA Oncology, Journal Year: 2023, Volume and Issue: 10(1), P. 43 - 43

Published: Nov. 22, 2023

Non-small cell lung cancer (NSCLC) with uncommon EGFR mutations is a rare subgroup, composing 14% of all mutations.

Language: Английский

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The potential of lazertinib and amivantamab combination therapy as a treatment strategy for uncommon EGFR-mutated NSCLC

Cell Reports Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 101929 - 101929

Published: Jan. 1, 2025

Language: Английский

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Pragmatic Randomized Study of Afatinib Versus Chemotherapy for Patients With Non–Small Cell Lung Cancer With Uncommon Epidermal Growth Factor Receptor Mutations: ACHILLES/TORG1834

Journal of Clinical Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

PURPOSE To our knowledge, the ACHILLES/TORG1834 trial is first randomized study comparing afatinib and chemotherapy in patients with non–small cell lung cancer (NSCLC) harboring sensitizing uncommon epidermal growth factor receptor ( EGFR ) mutations. METHODS This randomized, open-label was performed at 51 Japanese institutions recruited treatment-naïve nonsquamous NSCLC mutations, excluding exon 20 insertions T790M Patients were randomly assigned 2:1 to receive (30 or 40 mg orally, treating physician's discretion) a combination of platinum (cisplatin carboplatin) pemetrexed, followed by pemetrexed maintenance. The primary end point progression-free survival (PFS). Secondary points included objective response rate (ORR), overall survival, safety. A prespecified interim analysis planned provide clinically meaningful information promptly, along crossover recommendation if necessary. RESULTS total 109 enrolled between March 2019 February 2023. In analysis, Data Safety Monitoring Committee recommended early termination. median PFS significantly longer receiving than those undergoing (10.6 v 5.7 months; hazard ratio, 0.421 [95% CI, 0.251 0.706]; P = .0010). ORRs similar across population among participants major (G719X, L861Q, S768I), compound, other mutations (61.7%, 55.8%, 72.7%, 60.0%, respectively). most common grade 3 higher adverse events diarrhea, paronychia, rash for afatinib, appetite loss nausea chemotherapy. CONCLUSION Afatinib should be considered standard initial therapy

Language: Английский

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Clinical Outcomes of Afatinib Versus Osimertinib in Patients With Non-Small Cell Lung Cancer With Uncommon EGFR Mutations: A Pooled Analysis

The Oncologist, Journal Year: 2023, Volume and Issue: 28(6), P. e397 - e405

Published: April 28, 2023

Abstract Background The purpose of this analysis was to investigate the effectiveness afatinib compared that osimertinib in patients with non-small cell lung cancer (NSCLC) who harbored uncommon epidermal growth factor receptor (EGFR) mutations. Methods A PubMed database-based literature review conducted retrieve related studies. Patients harboring EGFR mutations besides deletion exon 19 (19del) and point mutation L858R were included analysis. primary outcome events objective response rate (ORR) progression-free survival (PFS). Propensity score matching (PSM) at a ratio 1:1 used between groups control confounding factors. Uncommon categorized into 4 groups: insertion 20 (ex20ins), non-ex20ins single mutations, compound 19del or L858R, without L858R. Results After PSM, 71 either group matched. had an ORR 60.6%, slightly higher than group’s (50.3%), difference not statistically significant (P = .610). However, showed significantly superior PFS benefit (11.0 vs. 7.0 months, P .044). In addition, yield best PFS, following treatment (ORR: 76.7%, mPFS: 14.1 months) 68.8%, 15.1 months). Moreover, there no terms cohort treated osimertinib, regardless whether brain metastases. Conclusions Both displayed favorable clinical activities toward Afatinib more profound durable although efficacy advantage observed.

Language: Английский

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EGFR exon 20 insertion mutations and ERBB2 mutations in lung cancer: a narrative review on approved targeted therapies from oral kinase inhibitors to antibody-drug conjugates

Translational Lung Cancer Research, Journal Year: 2023, Volume and Issue: 12(7), P. 1590 - 1610

Published: July 1, 2023

This review will provide an overview of

Language: Английский

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Perioperative Treatment Strategies in EGFR-Mutant Early-Stage NSCLC: Current Evidence and Future Challenges

Journal of Thoracic Oncology, Journal Year: 2023, Volume and Issue: 19(2), P. 199 - 215

Published: Sept. 30, 2023

Language: Английский

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