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

Journal of Thoracic Oncology, Год журнала: 2024, Номер 19(7), С. 973 - 983

Опубликована: Март 16, 2024

Язык: Английский

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The changing treatment landscape of EGFR-mutant non-small-cell lung cancer

Nature Reviews Clinical Oncology, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 29, 2024

Язык: 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, Год журнала: 2025, Номер unknown, С. 101929 - 101929

Опубликована: Янв. 1, 2025

Язык: Английский

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Detection of Overlooked Rare EGFR Mutations in Non‐small Cell Lung Cancer Using Multigene Testing

Thoracic Cancer, Год журнала: 2025, Номер 16(3)

Опубликована: Фев. 1, 2025

ABSTRACT Background Recognizing rare molecular variants of driver mutations poses a challenge in precision oncology, particularly for treatment non‐small cell lung cancer (NSCLC). In this study, we aimed to determine whether Oncomine Dx Target Test Multi‐CDx System (ODxTT), the most widely used genetic test NSCLC Japan, potentially overlooks druggable EGFR mutations. Materials and Methods Among 418 patients who underwent testing using ODxTT at our hospital, 267 were diagnosed with adenocarcinoma. No reported 82 these cases. For cases, searched exons 18–21 by examining binary alignment map file. Once mutation was identified, its pathological significance evaluated ClinVar database had overlooked any actionable Results Mutations 19 18 identified six four respectively. Three, six, none detectable Cobas Mutation v2, Lung Cancer Compact Panel, Amoy Dx, Of 10 patients, five subsequently treated TKI; three showed partial response, one stable disease, progressive disease. Conclusions failed identify mutations, accounting 12.2% (10/82) cases initially as not carrying Therefore, comprehensive genomic profiling should be actively performed early high clinical suspicion

Язык: Английский

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Lung Cancer: Targeted Therapy in 2025

Current Oncology, Год журнала: 2025, Номер 32(3), С. 146 - 146

Опубликована: Март 2, 2025

Lung cancer treatment has changed in the last twenty years since discovery of EGFR mutations. In this article, we will review current state art for non-small cell lung (NSCLC) actionable genomic alterations (AGA). AGAs are mostly found adenocarcinomas, a subtype cancers. We focus on mutations, ALK fusions, ROS1 BRAF V600E MET exon 14-skipping RET KRAS G12C ERBB2 mutations (also called HER2 mutations), and NTRK fusions. also touch key toxicities associated with these medications. Treatments available metastatic stage, but discuss adjuvant therapy as well stage III post-chemoradiotherapy cancer.

Язык: 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, Год журнала: 2025, Номер unknown

Опубликована: Апрель 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

Язык: 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, Год журнала: 2024, Номер 30(15), С. 3128 - 3136

Опубликована: Май 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

Язык: Английский

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Evolving Precision First-Line Systemic Treatment for Patients with Unresectable Non-Small Cell Lung Cancer

Cancers, Год журнала: 2024, Номер 16(13), С. 2350 - 2350

Опубликована: Июнь 26, 2024

First-line systemic therapy for patients with advanced or metastatic non-small cell lung cancer (NSCLC) has rapidly evolved over the past two decades. First, molecularly targeted a growing number of

Язык: Английский

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Activity of osimeRTInib in non-small-cell lung Cancer with UNcommon epidermal growth factor receptor mutations: retrospective Observational multicenter study (ARTICUNO)

ESMO Open, Год журнала: 2024, Номер 9(6), С. 103592 - 103592

Опубликована: Июнь 1, 2024

•Largest dataset of NSCLC with uncommon EGFR alterations treated osimertinib.•Best outcomes compound uncommon–common mutations and G719X, L861X, or S768I.•Heterogeneous activity rarer mutations; no response at E709 residue.•Confirmed in the central nervous system, intracranial ORR 58%.•Amplification MET, TP53 mutations, E709K are putative mechanisms resistance. BackgroundOsimertinib represents standard care for treatment advanced non-small-cell lung cancer (NSCLC) harboring classical epidermal growth factor receptor (EGFR) constituting 80%-90% all alterations. In remaining cases, an assorted group (uEGFR) can be detected, which confer variable sensitivity to previous generations inhibitors, overall lower therapeutic activity. Data on osimertinib this setting limited strongly warranted.Patients methodsThe ARTICUNO study retrospectively evaluated data from patients uEGFR 21 clinical centers between August 2017 March 2023. analysis was carried out a descriptive aim. Investigators collected according RECIST version 1.1 criteria. The median duration response, progression-free survival (mPFS), were estimated by Kaplan–Meier method.ResultsEighty-six identified. Patients 'major' uEGFR, that is, S768I (n = 51), had rate (ORR) mPFS 50% 9 months, respectively. Variable registered cases 'minor' 27), 31% 4 Among seven exon 20 insertions, 14%, while best outcome among including least one mutation 13). Thirty presented brain metastases (BMs) 58% Amplification emerged after failure 18 available rebiopsy.ConclusionThe confirms especially those major even presence BMs. Alterations residue associated resistance osimertinib. Osimertinib warranted. method. Eighty-six rebiopsy.

Язык: Английский

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Expert consensus on the use of third-generation EGFR-TKIs in EGFR-mutated advanced non-small cell lung cancer with various T790M mutations post-resistance to first-/second-generation EGFR-TKIs

Therapeutic Advances in Medical Oncology, Год журнала: 2024, Номер 16

Опубликована: Янв. 1, 2024

Third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have emerged as the mainstay of treatment for advanced EGFR-mutant non-small cell lung cancer (NSCLC), effectively overcoming problems acquired threonine-to-methionine (T790M) mutations associated with first- or second-generation TKIs. Evidence from several studies suggests that these agents, including osimertinib and aumolertinib, also show potential benefits in T790M-negative unknown populations, particularly those brain metastases, where high permeability blood-brain barrier allows effective control intracranial lesions. Despite encouraging results, further high-quality research, prospective trials, is warranted to fully elucidate efficacy profiles third-generation TKIs NSCLC patients after second-line TKI failure. The present expert consensus highlights evolving role EGFR-TKIs therapeutic resistance optimizing patient outcomes.

Язык: Английский

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