Osimertinib: A Review in Completely Resected, Early-Stage, EGFR Mutation-Positive NSCLC

Frampton, James E.

doi:10.1007/s11523-022-00883-0

Cited by 5 publications

(2 citation statements)

References 42 publications

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“…NSCLC were non-metastatic cases and the extrapolation of our data to metastatic NSCLC remains to be demonstrated. Of notes, the management of early-stage resected NSCLC currently benefits from substantive progress, with growing interest for TKI and ICI in a peri-operative context ( 45 , 46 ).…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic FHITlow/pHER2high signature as a predictive factor of outcome and immunotherapy response in non-small cell lung cancer

et al. 2022

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IntroductionIn recent decades, the development of immunotherapy and targeted therapies has considerably improved the outcome of non-small cell lung cancer (NSCLC) patients. Despite these impressive clinical benefits, new biomarkers are needed for an accurate stratification of NSCLC patients and a more personalized management. We recently showed that the tumor suppressor fragile histidine triad (FHIT), frequently lost in NSCLC, controls HER2 receptor activity in lung tumor cells and that tumor cells from NSCLC patients harboring a FHITlow/pHER2high phenotype are sensitive to anti-HER2 drugs. Here, we sought to identify the transcriptomic signature of this phenotype and evaluate its clinical significance.Materials and methodsWe performed RNA sequencing analysis on tumor cells isolated from NSCLC (n=12) according to FHIT/pHER2 status and a functional analysis of differentially regulated genes. We also investigated the FHITlow/pHER2high signature in The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LUAD) (n=489) and lung squamous cell carcinoma (LUSC) (n=493) cohorts and used the tumor immune dysfunction and exclusion (TIDE) model to test the ability of this signature to predict response to immune checkpoint inhibitors (ICI).ResultsWe showed that up-regulated genes in FHITlow/pHER2high tumors were associated with cell proliferation, metabolism and metastasis, whereas down-regulated genes were related to immune response. The FHITlow/pHER2high signature was associated with the higher size of tumors, lymph node involvement, and late TNM stages in LUAD and LUSC cohorts. It was identified as an independent predictor of overall survival (OS) in LUAD cohort. FHITlow/pHER2high tumors were also predictive of poor response to ICI in both LUAD and LUSC cohorts.ConclusionThese data suggest that ICI might not be a relevant option for NSCLC patients with FHITlow/pHER2high tumors and that anti-HER2 targeted therapy could be a good therapeutic alternative for this molecular subclass with poorer prognosis.

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Section: Discussionmentioning

confidence: 99%

Transcriptomic FHITlow/pHER2high signature as a predictive factor of outcome and immunotherapy response in non-small cell lung cancer

et al. 2022

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“…Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are a targeted first-line treatment for patients with EGFR mutation-positive advanced NSCLC (8)(9)(10)(11). Several studies have shown that EGFR-TKIs as adjuvant therapy improve the prognosis of earlystage patients with EGFR exon 19 deletions and L858R mutations (12)(13)(14). In addition to classical EGFR mutations, atypical EGFR mutations have been identified in 10-30% of patients with NSCLC (15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

Structure-based classification of EGFR mutations in operable pre-invasive and invasive non-small cell lung cancer: a cross-sectional study

Wang¹,

Cao²,

Qin³

et al. 2022

J Thorac Dis

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Background: It has been reported that the structure-based approach for defining functional groups of epidermal growth factor receptor (EGFR) mutations predicts the efficacy of EGFR inhibitors better than the traditional exon-based approach in the advanced stage. However, less is known about this structure-based classification of EGFR mutations in operable early-stage lung adenocarcinoma.Methods: Non-small cell lung cancer (NSCLC) patients with pathological stage I-III or adenocarcinoma in situ (AIS) who had EGFR mutations identified in NGS testing were recruited. Both exon-based and structure-based groupings of EGFR mutations were compared between the AIS and stage I-III patients using Fisher's exact test. Results:In total 1,012 patients including 66 AIS and 946 stage I-III patients were analyzed in the study.A total of 1185 EGFR mutations were identified in the 1,012 NSCLC patients, of whom 84.39% harbored a single EGFR mutation and 15.61% harbored complex EGFR mutations. As expected, L858R was more common than 19del in our population (39.33% vs. 35.67%). Interestingly, concurrent L858R and 19del mutations were identified in 9 patients (0.89%), and all these patients were diagnosed with multiple primary lung cancer. A higher percentage of atypical EGFR mutations was identified in the AIS cohort than in the stage I-III NSCLC cohort (33.33% vs. 21.66%, P=0.03). According to the structure-based classification of EGFR mutations, 86.07%, 7.11%, 5.04%, and 1.78% of the EGFR mutations were classified as classicallike, P-loop and α C-helix compressing (PACC), exon 20 insertions (Ex20ins), and T790M-like mutations, respectively. The composition of EGFR mutations was different between patients <65 and ≥65 years (P=0.0267) but similar between patients with AIS and stage I-III NSCLC (P=0.1436). However, a higher percentage of Ex20ins occurred in younger (<65 years) patients, nonsmoking patients, and patients with AIS (6.7% vs. 2.5%, P=0.003; 5.8% vs. 0.8%, P=0.0107; and 10.6% vs. 4.7%, P=0.0423, respectively).Conclusions: This large cross-sectional study delineated the structure-based classification of EGFR mutations in patients with operable NSCLC. While the traditional exon-based EGFR grouping showed difference between AIS and stage I-III NSCLC cohort, no difference was identified in the structural approach. Which approach had better prediction of targeted therapy efficacy in adjuvant settings warrants further investigation.

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Targeting the EGFR/RAS/RAF signaling pathway in anticancer research: a recent update on inhibitor design and clinical trials (2020–2023)

Hajjo,

Sabbah,

Bardaweel

et al. 2024

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Osimertinib: A Review in Completely Resected, Early-Stage, EGFR Mutation-Positive NSCLC

Cited by 5 publications

References 42 publications

Transcriptomic FHITlow/pHER2high signature as a predictive factor of outcome and immunotherapy response in non-small cell lung cancer

Transcriptomic FHITlow/pHER2high signature as a predictive factor of outcome and immunotherapy response in non-small cell lung cancer

Structure-based classification of EGFR mutations in operable pre-invasive and invasive non-small cell lung cancer: a cross-sectional study

Targeting the EGFR/RAS/RAF signaling pathway in anticancer research: a recent update on inhibitor design and clinical trials (2020–2023)

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