Uncommon EGFR mutations in non-small-cell lung cancer: A systematic literature review of prevalence and clinical outcomes

John, Thomas; Taylor, Aliki; Wang, Huifen; Eichinger, Christian; Freeman, Caroline; Ahn, Myung‐Ju

doi:10.1016/j.canep.2021.102080

Cited by 24 publications

(31 citation statements)

References 73 publications

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“…In the present study, we found a higher frequency of the p.L861X mutation with 35.3% and 14.7% of cases carrying the p.L861Q and the p.L861R, respectively. In a recent study, John et al reported that the prevalence of uncommon EGFR mutations varied between 1.0% and 18.2% in Asia and South America [ 37 ]. According to this study, the most frequently reported uncommon mutations were G719X (0.9–4.8%), exon 20 insertions (0.8–4.2%), L861X (0.5–3.5%), and S768I (0.5–2.5%).…”

Section: Discussionmentioning

confidence: 99%

Predominance of the Rare EGFR Mutation p.L861Q in Tunisian Patients with Non-Small Cell Lung Carcinoma

Abdelmaksoud‐Dammak

Ammous-Boukhris

Saadallah-Kallel

et al. 2022

Genes

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Objectives: Several new cancer therapies targeting signaling pathways involved in the growth and progression of cancer cells were developed as personalized medicine. Our study aimed to identify epidermal growth factor receptor (EGFR) mutations for TKI treatment in non-small-cell lung cancer (NSCLC) Tunisian patients. Methods: Analysis of the TKI sensitivity mutations in exons 18 to 21 of the EGFR gene and exon 15 of the B-raf gene was performed in 79 formalin fixed-paraffin embedded (FFPE) NSCLC samples using pyrosequencing. Results: EGFR mutations were detected in 34 cases among 79 (43%), with the predominance of the L861Q in exon 21 found in 35.3% of the cases (12 out of 34). Deletions in exon 19 were found in 8 cases (23.5%), and only one young male patient had the T790M mutation. Three patients harbored composite EGFR mutations (p.E746_A750del/p.L861R, p.E746_S752>V/p.S768I, and p.G719A/p.L861Q). Furthermore, the EGFR mutated status was significantly more frequent in female patients (p = 0.019), in non-smoker patients (p = 0.008), and in patients with metastasis (p = 0.044). Moreover, the B-raf V600E was identified in 5 EGFR negative patients among 39 analyzed samples (13.15%). Conclusion: The p.L861Q localized in exon 21 of the EGFR gene was the most common mutation identified in our patients (35.3%), whereas the “classic” EGFR mutations such as Del19 and p.L858R were found in 23.5% and 11.7% of the cases, respectively. Interestingly, most of p.L861X mutation-carrying patients showed good response to TKI treatment. Altogether, our findings suggest a particular distribution of the EGFR-TKIs sensitivity mutations in Tunisian NSCLC patients.

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Section: Discussionmentioning

confidence: 99%

Predominance of the Rare EGFR Mutation p.L861Q in Tunisian Patients with Non-Small Cell Lung Carcinoma

Abdelmaksoud‐Dammak

Ammous-Boukhris

Saadallah-Kallel

et al. 2022

Genes

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“…First- to third-generation EGFR tyrosine kinase inhibitors (TKIs) approved in NSCLC patients harboring activating EGFR mutations demonstrated only limited efficacy with an ORR <10% in the EGFR Exon20ins population. 7 , 10 , 11 Additionally, those patients have a dismal prognosis and inferior PFS compared to classical EGFR-mutated NSCLC patients (14 versus 2 months, P < 0.0001). 11 …”

Section: Egfr Exon 20 Insertions In Nsclcmentioning

confidence: 97%

“… 4 , 5 EGFR Exon20ins mutations are detected in ∼0.1%-4% of the NSCLC cases. 6 , 7 While common EGFR mutations are more frequently diagnosed in Asian patients compared to Caucasian ones, no such distribution is found in EGFR Exon20ins patients. 8 Female gender and smoking status (never smoker) seem to be associated with EGFR Exon20ins mutations.…”

Section: Egfr Exon 20 Insertions In Nsclcmentioning

confidence: 98%

Will CHRYSALIS turn into a butterfly?

Fuereder

2022

ESMO Open

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“…Numerous clinical trials have proved that, compared to conventional platinum-based chemotherapy, epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) produce better objective response rates (ORR) and progression-free survival (PFS), as well as overall survival (OS) (Mitsudomi et al, 2010;Zhou et al, 2011;Wu et al, 2014;Yang et al, 2014;Paz-Ares et al, 2017;Soria et al, 2018;Ramalingam et al, 2020). Additionally, other types of EGFR mutations, called uncommon EGFR mutations (ucm-EGFRms), were also been found, and account for approximately 10%-15% of EGFR mutations (Russo et al, 2019;John et al, 2022). Owing to the very small sample size and a high degree of heterogeneity, the effectiveness of EGFR-TKIs in patients having um-EGFRms remains uncertain (Russo et al, 2019;Zhang et al, 2020;John et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, other types of EGFR mutations, called uncommon EGFR mutations (ucm-EGFRms), were also been found, and account for approximately 10%-15% of EGFR mutations (Russo et al, 2019;John et al, 2022). Owing to the very small sample size and a high degree of heterogeneity, the effectiveness of EGFR-TKIs in patients having um-EGFRms remains uncertain (Russo et al, 2019;Zhang et al, 2020;John et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

Insensitivity to T790M mutation? A pooled analysis of outcomes following osimertinib for the treatment of NSCLC patients harboring uncommon epidermal growth factor receptor mutation

Wang

et al. 2022

Front. Pharmacol.

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Background: In this pooled analysis, the aim was to investigate the clinicopathological characteristics of patients with uncommon epidermal growth factor receptor (EGFR) (ucm-EGFRms) along with their treatment responses and survival following osimertinib treatment.Methods: Univariate chi-square analysis was conducted to analyze the correlation between clinical characteristics, EGFR mutation type, and treatment response, and the Kaplan-Meier method was applied for survival analysis. Univariate logistic regression model and Cox proportional hazards model were performed to compare the efficacy and prognosis in subgroup analysis.Results: Seventy-two NSCLC patients in total were included in this pooled analysis. The objective response rate (ORR) for osimertinib treatment was 57.0%, with a median PFS of 7.1 months. Twenty-eight patients received osimertinib as first-line therapy with an ORR of 67.9%, which was higher than that in patients who received osimertinib as second- or later-line therapy, and their response rate was 50%, nevertheless, no statistically significant differences were found (p = 0.139). However, patients who received first-line osimertinib showed a more significant PFS benefit than those who received second- or later-line therapy (mPFS: 16.8 months vs 6.0 months HR: 2.453, 95%CI: 1.285-4.682, p =0.004). Subgroup analysis showed that patients with a single, non-ex20ins, ucm-EGFRm displayed a superior efficacy advantage and favorable survival benefit following osimertinib treatment, with an ORR of 68.8% and an mPFS at 15.1 months. By contrast, patients with a multiple ucm-EGFRm that contain T790M exhibited the worst outcome of osimertinib treatment, with an ORR of 47.6% and an mPFS of only 3.6 months, respectively.Conclusion: Patients with um-EGFRms exhibit favorable but inconsistent responses and survival outcomes following osimertinib treatment, which is closely related to the mutation pattern and cooccurring partner mutant genes. Administering osimertinib for the treatment of patients with um-EGFRm might be considered an effective treatment option in some circumstances.

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Uncommon EGFR mutations in non-small-cell lung cancer: A systematic literature review of prevalence and clinical outcomes

Cited by 24 publications

References 73 publications

Predominance of the Rare EGFR Mutation p.L861Q in Tunisian Patients with Non-Small Cell Lung Carcinoma

Predominance of the Rare EGFR Mutation p.L861Q in Tunisian Patients with Non-Small Cell Lung Carcinoma

Will CHRYSALIS turn into a butterfly?

Insensitivity to T790M mutation? A pooled analysis of outcomes following osimertinib for the treatment of NSCLC patients harboring uncommon epidermal growth factor receptor mutation

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