Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors and Lung Cancer: History, Epidemiology, and Market Outlook

Miles, Brittany; Mackey, James

doi:10.7759/cureus.13470

Cited by 5 publications

(4 citation statements)

References 19 publications

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“…Of note, in our study, 26 patients (13.5% of those tested) had tumors harboring the T790M mutation in the same tissue sample used for EGFR mutation analysis; despite a very few amount of mutated alleles being detected by NGS assay, such a subset of patients presented a consistently worse prognosis in comparison with cases who did not had the T790M variant. The EGFR-T790M mutation alone accounts for up to 50% of resistances in TKIs, which affect the majority of patients within the first year of treatment, and is considered quite rare at diagnosis, being the main mechanism of acquired (or secondary) drug resistance [ 14 – 16 ]. In this sense, our data show that, even if such a mutation is present at sub-clonal level in about one tenth of cases at the time of diagnosis, it may somehow affect the tumor behavior by causing intrinsic (or primary) drug resistance and inducing poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

Global prognostic impact of driver genetic alterations in patients with lung adenocarcinoma: a real-life study

et al. 2022

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Background Advanced lung adenocarcinoma (LAC) is one of the most lethal malignancies worldwide. The aim of this study was to evaluate the global survival in a real-life cohort of patients with LAC harboring driver genetic alterations. Methods A series of 1282 consecutive Sardinian LAC patients who underwent genetic testing from January 2011 through July 2016 was collected. Molecular tests were based on the clinical needs of each single case (EGFR-exon18/19/21, ALK, and, more recently, BRAF-exon15), and the availability of tissue (KRAS, MET, and presence of low-frequency EGFR-T790M mutated alleles at baseline). Results The mean follow-up time of the patients was 46 months. EGFR, KRAS, and BRAF mutations were detected in 13.7%, 21.3%, and 3% of tested cases, respectively; ALK rearrangements and MET amplifications were found respectively in 4.7% and 2% of tested cases. As expected, cases with mutations in exons 18–21 of EGFR, sensitizing to anti-EGFR tyrosine kinase inhibitors (TKIs) agents, had a significantly longer survival in comparison to those without (p < 0.0001); conversely, KRAS mutations were associated with a significantly lower survival (p = 0.0058). Among LAC patients with additional tissue section available for next-generation sequencing (NGS)-based analysis, 26/193 (13.5%) patients found positive for even low-rate EGFR-T790M mutated alleles at baseline were associated with a highly significant lower survival in comparison to those without (8.7 vs. 47.4 months, p < 0.0001). Conclusions In addition to its predictive value for addressing targeted therapy approaches, the assessment of as more inclusive mutation analysis at baseline may provide clues about factors significantly impacting on global survival in advanced LAC patients.

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Section: Discussionmentioning

confidence: 99%

Global prognostic impact of driver genetic alterations in patients with lung adenocarcinoma: a real-life study

et al. 2022

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“…Patients with non‐small cell lung cancer (NSCLC) typically present with advanced‐stage disease at diagnosis and have poor prognoses. However, the introduction of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has revolutionized the management of EGFR ‐mutated advanced NSCLC, and they are currently recommended as the first‐line treatment of choice in several international guidelines 2,3 . Clinical trials and real‐world evidence have shown that EGFR‐TKIs significantly improve progression‐free (PFS) and overall (OS) survival compared to historical standard platinum‐based chemotherapy in patients with EGFR ‐mutated advanced NSCLC 4,5 .…”

Section: Introductionmentioning

confidence: 99%

“…However, the introduction of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has revolutionized the management of EGFR ‐mutated advanced NSCLC, and they are currently recommended as the first‐line treatment of choice in several international guidelines. 2 , 3 Clinical trials and real‐world evidence have shown that EGFR‐TKIs significantly improve progression‐free (PFS) and overall (OS) survival compared to historical standard platinum‐based chemotherapy in patients with EGFR ‐mutated advanced NSCLC. 4 , 5 In addition, previous studies have shown that EGFR‐TKIs significantly reduce the symptomatic burden and improve the quality of life of affected patients.…”

Section: Introductionmentioning

confidence: 99%

Survival outcomes of east Asian patients with advanced non‐small cell lung cancer treated with first‐line EGFR tyrosine kinase inhibitors: A network meta‐analysis of real‐world evidence

Chang,

Huang,

Tseng

et al. 2023

Thoracic Cancer

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BackgroundThe comparative efficacies of different generation tyrosine kinase inhibitors (TKIs) in epidermal growth factor receptor (EGFR)‐mutated advanced non‐small cell lung cancer (NSCLC) remain largely unknown. Moreover, whether one EGFR‐TKI confers superior survival remains unclear, especially in East Asians. We conducted a network meta‐analysis (NMA) comparing the survival outcomes of East Asian patients with advanced NSCLC treated with first‐line EGFR‐TKIs.MethodsThe NMA included observational real‐world evidence studies on adult patients with EGFR‐mutated advanced NSCLC who received first (gefitinib and erlotinib), second (afatinib), or third (osimertinib) generation EGFR‐TKIs as frontline therapy. Studies were identified through an online bibliographic search of Medline articles in the PubMed, SCOPUS, Web of Science, and Cochrane Library databases.ResultsFor overall survival (OS), afatinib had significantly better hazard ratios (HRs) than osimertinib (HR: 0.46, 95% confidence interval [CI]: 0.23–0.91), gefitinib (HR: 0.56, 95% CI: 0.43–0.72), and erlotinib (HR: 0.71, 95% CI: 0.54–0.92). For progression‐free survival (PFS), afatinib had significantly better HRs than gefitinib (HR: 0.45, 95% CI: 0.36–0.56) and erlotinib (HR: 0.63, 95% CI: 0.49–0.81). Moreover, afatinib was most likely to achieve the longest OS (81.3%), followed by erlotinib (13%), osimertinib, and gefitinib. Furthermore, afatinib was most likely to achieve the longest PFS (48.3%), followed by osimertinib (34.9%) and erlotinib.ConclusionsThis real‐world evidence shows that afatinib confers better survival than other first‐line EGFR‐TKIs in East Asian patients with advanced NSCLC.

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“…Lung adenocarcinoma (LUAD) is the main subtype of NSCLC, accounting for about 60% of all NSCLC cases ( 1 - 3 ). Many potential therapeutic targets and corresponding targeted drugs have been discovered and applied in clinics for the treatment of LUAD, including epidermal growth factor receptor (EGFR), fibroblast growth factor receptor, and insulin-like growth factor ( 4 - 6 ). Nevertheless, there is an urgent need to discover more potential and effective target genes in LUAD to further improve the treatment strategy.…”

Section: Introductionmentioning

confidence: 99%

PTS is activated by ATF4 and promotes lung adenocarcinoma development via the Wnt pathway

Ma¹,

Wang²,

Li³

et al. 2022

Transl Lung Cancer Res

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Background: The effects and mechanism of 6-pyruvoyl-tetrahydropterin synthase (PTS) on lung adenocarcinoma (LUAD) were studied in LUAD cells and mice with subcutaneously transplanted tumors. Methods: PTS level in tissues and cells was tested by immunohistochemistry, western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). The impacts of PTS on cell viability, proliferation, apoptosis, invasion, and migration were determined by Cell Counting Kit-8 (CCK-8), colony formation assay, flow cytometry, transwell assay, and wound healing assay, respectively. The Cancer Genome Atlas (TCGA) analysis and dual luciferase assay were conducted to predict and verify the relationship between PTS and activating transcription factor 4 (ATF4). A mouse model was established by subcutaneous injection with cancer cells. Tumor volume was calculated as V = ab 2 /2. Ki67 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were used to measure cell proliferation and apoptosis in tumors.Results: PTS was highly expressed in LUAD. Higher PTS level was correlated with late clinical stages and poor survival of patients. Down-regulation of PTS inhibited the viability and proliferation and induced apoptosis of LUAD cells. PTS was activated by ATF4, and up-regulation of ATF4 reversed the inhibitory effect of PTS silencing on LUAD cells. Silencing of PTS inhibited the Wnt pathway. Down-regulation of PTS inhibited tumor growth in mice.Conclusions: PTS was highly expressed in LUAD. PTS was activated by ATF4 and promoted LUAD development via the Wnt pathway.

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Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors and Lung Cancer: History, Epidemiology, and Market Outlook

Cited by 5 publications

References 19 publications

Global prognostic impact of driver genetic alterations in patients with lung adenocarcinoma: a real-life study

Global prognostic impact of driver genetic alterations in patients with lung adenocarcinoma: a real-life study

Survival outcomes of east Asian patients with advanced non‐small cell lung cancer treated with first‐line EGFR tyrosine kinase inhibitors: A network meta‐analysis of real‐world evidence

PTS is activated by ATF4 and promotes lung adenocarcinoma development via the Wnt pathway

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