Novel Combination of Therapeutic Approaches in Advanced NSCLC with EGFR Activating Mutations DOI Open Access
Danilo Rocco, Luigi Della Gravara,

Maria Cristina Boccia

et al.

Targets, Journal Year: 2024, Volume and Issue: 2(3), P. 237 - 249

Published: Sept. 7, 2024

The vast majority of advanced NSCLC cases are histologically represented by adenocarcinomas. EGFR activating mutations (exon 19 deletions, exon 21 L858R substitutions, 20 insertions) represent one the most common druggable alterations. Since erlotinib’s FDA approval in 2013, EGFR-TKIs have a staple EGFR+ treatment, with osimertinib representing latest major FDA-approved third-generation EGFR-TKI. In recent years, however, several preclinical data highlighted promising results regarding combination therapies involving plus chemotherapy, and various clinical trials confirmed these results. addition, 2021, amivantamab was first mAb for treatment patients; according to some extremely up-to-date trials, chemotherapy is also associated superior Therefore, this paper aims provide comprehensive review both bases evidence patients.

Language: Английский

Unveiling the Landscape of Uncommon EGFR Mutations in NSCLC-A Systematic Review DOI Creative Commons
Maxime Borgeaud, Kaushal Parikh, Giuseppe Luigi Banna

et al.

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

Published: March 16, 2024

Language: Английский

Citations

24
The changing treatment landscape of EGFR-mutant non-small-cell lung cancer DOI
Fei Zhou, Haoyue Guo, Yang Xia

et al.

Nature Reviews Clinical Oncology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 29, 2024

Language: Английский

Citations

10
The potential of lazertinib and amivantamab combination therapy as a treatment strategy for uncommon EGFR-mutated NSCLC DOI Creative Commons
Seung Yeon Oh, Sewon Park, Seo-Young Lee

et al.

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

Published: Jan. 1, 2025

Language: Английский

Citations

1
Detection of Overlooked Rare EGFR Mutations in Non‐small Cell Lung Cancer Using Multigene Testing DOI Creative Commons

N. Shiraishi,

Takayuki Takahama, Kazuko Sakai

et al.

Thoracic Cancer, Journal Year: 2025, Volume and Issue: 16(3)

Published: Feb. 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

Language: Английский

Citations

1
Pragmatic Randomized Study of Afatinib Versus Chemotherapy for Patients With Non–Small Cell Lung Cancer With Uncommon Epidermal Growth Factor Receptor Mutations: ACHILLES/TORG1834 DOI
Satoru Miura, Hiroshi Tanaka, Toshihiro Misumi

et al.

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

Citations

1
Evolving Precision First-Line Systemic Treatment for Patients with Unresectable Non-Small Cell Lung Cancer DOI Open Access
Tianhong Li, Weijie Ma,

Ebaa Al-Obeidi

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(13), P. 2350 - 2350

Published: June 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

Language: Английский

Citations

5
From Rarity to Reality: Osimertinib's Promising Horizon in Treating Uncommon EGFR Mutations in Non-Small Cell Lung Cancer DOI
Akito Fukuda, Yusuke Okuma

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

Citations

4
Advances in the Study of Interstitial Lung Disease Risk in Non-Small Cell Lung Cancer with EGFR-TKI Combination Therapy DOI

子钰 郭

Advances in Clinical Medicine, Journal Year: 2025, Volume and Issue: 15(03), P. 1817 - 1823

Published: Jan. 1, 2025

Language: Английский

Citations

0
Osimertinib vs. Afatinib in 1L therapy of atypical EGFR-mutated metastatic non-small cell lung cancer (mNSCLC): A multi-institution, real-world survival analysis DOI Creative Commons
Adam Barsouk, Omar Elghawy,

Alan G. Watts

et al.

Lung Cancer, Journal Year: 2025, Volume and Issue: 203, P. 108551 - 108551

Published: April 19, 2025

Language: Английский

Citations

0
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 DOI
Jonathan N. Priantti, Yu Fujiwara, Francisco Cézar Aquino de Moraes

et al.

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

Citations

3