Real‐world clinical analysis in 190 advanced NSCLC patients with uncommon EGFR mutations: A multi‐center study

Qin, Yi; Long, Yaling; Tang, Yuan; Tian, Ye; Li, Juan; Duan, Ping; Luo, Jieyan; Yu, Min; Li, Yanying; Zhou, Xiaojuan; Wang, Ke; Gong, Youling; Peng, Feng; Zhu, Jiang; Liu, Yongmei; Zhou, Lin; Lu, You; Huang, Meijuan

doi:10.1111/cas.15769

Cited by 8 publications

(2 citation statements)

References 46 publications

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“…According to one study, patients with uncommon EGFR mutations are more likely to have MET amplification than T790M mutation after afatinib resistance. In patients with uncommon mutations, the incidence of acquired EGFR T790M mutations was significantly lower than that of 19del and L858R mutations [ 61 ]. Another study with a small sample size suggests that EGFR T790M (11%) and FGFR1 amplification (11%), and MET amplification (11%), followed by CDK4 amplification (7%), PI3KCA activation (7%), RET fusion (4%), and BRAF mutation (4%) may be the main mechanisms of resistance in EGFR G719X/L861Q/S768I patients treated with afatinib [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

Afatinib for the Treatment of NSCLC with Uncommon EGFR Mutations: A Narrative Review

et al. 2023

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Afatinib, the world’s first irreversible ErbB family (containing four different cancer cell epidermal growth factor receptors, including EGFR, HER2, ErbB3, and ErbB4) inhibitor, is a second-generation oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). It can be used as a first-line treatment for locally advanced or metastatic non-small-cell lung cancer (NSCLC) with an EGFR-sensitive mutation or for patients with locally advanced or metastatic squamous lung cancer whose disease progresses during or after platinum-containing chemotherapy. Currently, with the use of third-generation EGFR-TKIs, afatinib is no longer clinically indicated as the first choice for patients with NSCLC who have EGFR-sensitive mutations. However, afatinib showed a considerable inhibitory effect in NSCLC patients with uncommon EGFR mutations (G719X, S768I, and L861Q) according to a combined post hoc analysis of the LUX-Lung2/3/6 trials. With the development of genetic testing technology, the detection rate of uncommon EGFR mutations is increasing. The aim of this paper is to describe in detail the sensitivity of rare EGFR mutations to afatinib and to provide information and a reference for those suffering from advanced NSCLC who have uncommon EGFR mutations.

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Section: Discussionmentioning

confidence: 99%

Afatinib for the Treatment of NSCLC with Uncommon EGFR Mutations: A Narrative Review

et al. 2023

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“…This resistance-inducing mutation is colloquially referred to as a “resistance mutation,” excluding the A763–764insFQEA variant, which accounts for approximately 6% of EGFR exon 20 insertions. Findings from a multicenter trial ( 22 ) reveal that, in the first-line treatment with EGFR-TKIs, patients harboring EGFR exon 20 insertion mutations exhibit a median progression-free survival (mPFS) of 5.7 months and an mOS of 19.0 months. In contrast, non-EGFR exon 20 insertion patients display an mPFS of 9.0 months, and an mOS of 29.9 months.…”

Section: Introductionmentioning

confidence: 99%

The current landscape, advancements, and prospects in the treatment of patients with EGFR exon 20 insertion mutations warrant scientific elucidation

Man,

Sun,

Chen

et al. 2024

Front. Oncol.

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Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations are the third most prevalent mutation in non-small cell lung cancer (NSCLC), following the 19del and L858R mutations. The unique nature of the EGFR ex20ins mutation poses challenges for the effectiveness of first- and second-generation EGFR tyrosine kinase inhibitors (TKIs). As a result, chemotherapy remains the primary and more effective treatment approach. However, with advancements in time and technology, numerous experimental studies have revealed the potential of novel drugs and therapies to have stronger inhibitory effects on EGFR ex20ins mutations. In this comprehensive review, we provide an overview of the current treatment landscape, recent advancements, and the prospects for patients with advanced NSCLC characterized by EGFR ex20ins mutations.

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Efficacy and Safety of Chemotherapy or EGFR‐TKIs as First‐Line Therapy in NSCLC Patients Harboring Non‐Ex 20 Ins Uncommon EGFR Mutations: A Retrospective Study in China

Liao,

Bai,

et al. 2024

Cancer Medicine

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BackgroundUncommon EGFR mutations are a kind of heterogeneous group of mutations with various responses to EGFR‐TKIs and are often excluded from most prospective clinical trials. In this real‐world retrospective study, we retrospectively compared the efficacy and safety of chemotherapy or various generations of EGFR‐TKIs as first‐line therapy in NSCLC Chinese patients harboring non‐ex 20 ins uncommon EGFR mutations.MethodsWe enrolled 139 NSCLC patients with non‐ex 20 ins uncommon EGFR mutations in this study retrospectively. Patients' clinical characteristics and the efficacy and safety of different first‐line therapies were analyzed and compared.ResultsOur data reviewed that for first‐line therapy, NSCLC patients harboring non‐ex 20 ins uncommon EGFR mutations benefited more from EGFR‐TKIs compared with chemotherapy. Afatinib performed with great efficacy for the majority of non‐ex 20 ins uncommon EGFR mutations (N = 43, ORR = 41.86%, mPFS = 13.5 months, mOS = 20.8 months), especially in L861Q mutation (mPFS = 18.4 months). Osimertinib also demonstrated efficacy in patients harboring non‐ex 20 ins uncommon EGFR mutations (N = 36, ORR = 27.78%, mPFS = 10.0 months, mOS = 21.0 months), especially in those without L861Q and G719X mutations (mPFS = 12.1 months). When treated with afatinib, patients harboring non‐ex 20 ins uncommon EGFR mutations should pay attention to the management of safety, especially for gastrointestinal‐related AE and rash, while osimertinib was safer.ConclusionTaking into account both efficacy and safety, afatinib and osimertinib are better choices than chemotherapy and first‐generation EGFR‐TKIs for NSCLC patients with non‐ex 20 ins uncommon EGFR mutations. L861Q showed a trend toward a better response to afatinib, while in those without L861Q and G719X mutations, osimertinib might be a better choice. Safety also should be a concern when choosing EGFR‐TKI for treatment, patients should pay attention to the management of safety when using afatinib while osimertinib is safer.

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Real‐world clinical analysis in 190 advanced NSCLC patients with uncommon EGFR mutations: A multi‐center study

Cited by 8 publications

References 46 publications

Afatinib for the Treatment of NSCLC with Uncommon EGFR Mutations: A Narrative Review

Afatinib for the Treatment of NSCLC with Uncommon EGFR Mutations: A Narrative Review

The current landscape, advancements, and prospects in the treatment of patients with EGFR exon 20 insertion mutations warrant scientific elucidation

Efficacy and Safety of Chemotherapy or EGFR‐TKIs as First‐Line Therapy in NSCLC Patients Harboring Non‐Ex 20 Ins Uncommon EGFR Mutations: A Retrospective Study in China

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