Efficacy and safety of afatinib for non-small-cell lung cancer: state-of-the-art and future perspectives

Sartori, Giulia; Belluomini, Lorenzo; Lombardo, Francesca; Avancini, Alice; Trestini, Ilaria; Vita, Emanuele; Tregnago, Daniela; Menis, Jessica; Bria, Emilio; Milella, Michèle; Pilotto, Sara

doi:10.1080/14737140.2020.1776119

Cited by 9 publications

(13 citation statements)

References 90 publications

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“…49 The safety profile in patients with squamous NSCLC is consistent with the known safety profile of afatinib, and includes diarrhoea, skin toxicities, fatigue and stomatitis as the most common side effects. 50 Overall, the incidence of adverse events was similar in the afatinib and erlotinib arms ( (Figure 1). Six patients required a dose reduction to 30 mg and three required a further reduction to 20 mg.…”

Section: Afatinib In Squamous Non-small Cell Lung Cancer: the Lux-lung 8 Trialmentioning

confidence: 82%

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Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in the Treatment of Patients with Non-small Cell Lung Cancer of Squamous Histology: Focus on Afatinib

Reguart¹,

Reyes²

2021

Oncology &Amp; Haematology

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Section: Afatinib In Squamous Non-small Cell Lung Cancer: the Lux-lung 8 Trialmentioning

confidence: 82%

“…of the patients (Table 3). 50 Mutations were detected in EGFR, HER2, ErbB3 (HER3), and ErbB4 (HER4), with each mutation being report in approximately 5-6% of patients. One patient had EGFR, HER2, and ErbB3 (HER3) mutations, and two patients had ErbB3 (HER3) and ErbB4 (HER4) mutations.…”

Section: Squamous Non-small Cell Lung Cancer: Erbb Pathway Dysregulationmentioning

confidence: 99%

Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in the Treatment of Patients with Non-small Cell Lung Cancer of Squamous Histology: Focus on Afatinib

Reguart¹,

Reyes²

2021

Oncology &Amp; Haematology

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“…Although targeted drugs have achieved enormous success in treating NSCLC, new chemotherapy is needed since the emerged drug resistance always hinders curative effects. 36 The fungal toxin (+)-chaetocin demonstrated strong antineoplastic activities against the tested lung large cell carcinoma cell lines H460 and H661 at submicromolar concentrations. Further research demonstrated that (+)-chaetocin effectively induced H460 apoptosis at 10-30 nM concentrations, while cell deaths occurred directly at 60 nM concentrations due to DNA duplication errors.…”

Section: Discussionmentioning

confidence: 97%

Marine toxin (+)‐chaetocin‐induced apoptosis of lung large cell carcinoma cell lines through cell cycle arrest via CDKN1A expression and replicative stress

Qian

Cao

2022

Clinical and Translational Dis

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“…Afatinib is an irreversibly mutant EGFR-TKI and the first-line FDA-approved treatment for locally advanced or metastatic NSCLC ( 6 ). While afatinib achieves superior efficacy in progression-free survival (PFS) and overall survival (OS) compared with conventional chemotherapy in NSCLC, progression inevitably occurs after EGFR TKI treatment for acquired resistance, which presents challenges in the treatment of NSCLC ( 7 , 8 ).…”

Section: Introductionmentioning

confidence: 99%

Identification and Validation of Afatinib Potential Drug Resistance Gene BIRC5 in Non-Small Cell Lung Cancer

Zhu

Zhou

et al. 2021

Front. Oncol.

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IntroductionResistance to second-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), afatinib, is the most significant challenge in the clinical management of non-small cell lung cancer (NSCLC), and the underlying mechanisms remain unclear.MethodsGenomic signatures that may confer afatinib resistance in NSCLC were identified via data mining of public databases and integrative bioinformatic analyses. Furthermore, acquired afatinib-resistant lung adenocarcinoma cell lines (HCC827 AR) were established by long-term exposure under afatinib in vitro for stepwise escalation. The expression of baculovirus IAP repeat protein 5 (BIRC5) was detected by western blot, and cellular viability of HCC827 AR was determined by CCK8.ResultsThrough integrative bioinformatic analyses of public datasets, overexpression of baculovirus IAP repeat protein 5 (BIRC5) was identified in both afatinib-resistant NSCLC cells and tissues, and BIRC5 overexpression was positively correlated with lymph node metastasis as well as pathological stage in NSCLC. Furthermore, NSCLC patients with BIRC5 overexpression showed poor survival outcomes. Immune infiltration analysis suggested that BIRC5 expression was significantly inversely correlated with tumor-infiltrating cell numbers and immune biomarker expression in NSCLC. The functions of genes co-expressed with BIRC5 were mainly enriched in cell cycle mitotic phase transition, double-strand break repair, and negative regulation of the cell cycle process signaling pathway. In addition, overexpression of BIRC5 protein was detected in afatinib-resistant cells by western blot, while BIRC5-expressing cells treated with BIRC5 inhibitor, YM155, were sensitive to afatinib.ConclusionsIn this study, we showed that overexpression of BIRC5 resulted in resistance to afatinib in NSCLC and BIRC5-specific inhibitors may overcome the resistant phenotype, indicating that dysregulation of the apoptotic cell death pathway may be the key mechanism underlying TKI resistance in the development of NSCLC.

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Efficacy and safety of afatinib for non-small-cell lung cancer: state-of-the-art and future perspectives

Cited by 9 publications

References 90 publications

Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in the Treatment of Patients with Non-small Cell Lung Cancer of Squamous Histology: Focus on Afatinib

Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in the Treatment of Patients with Non-small Cell Lung Cancer of Squamous Histology: Focus on Afatinib

Marine toxin (+)‐chaetocin‐induced apoptosis of lung large cell carcinoma cell lines through cell cycle arrest via CDKN1A expression and replicative stress

Identification and Validation of Afatinib Potential Drug Resistance Gene BIRC5 in Non-Small Cell Lung Cancer

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