Icotinib is as efficacious as gefitinib for brain metastasis of EGFR mutated non-small-cell lung cancer

Liu, Kejun; Jiang, Guanming; Zhang, Ailing; Li, Zhuanghua

doi:10.1186/s12885-020-6543-y

Cited by 11 publications

(9 citation statements)

References 45 publications

(46 reference statements)

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“…Overall, 4 clinical trials [17,18] and 4 retrospective analyses [19][20][21][22][23][24][25][26][27] were reviewed (Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…Another first-generation TKI, Icotinib, approved and distributed exclusively in China, has been retrospectively compared to Gefitinib in a limited series of metastatic NSCLC patients [21]. The intracranial PFS (iPFS) was not statistically different between patients treated with either Icotinib (n = 21) or Gefitinib (n = 22) (8.4 vs. 10.6 months, P = 0.17), nor were ORR and AEs.…”

Section: Comparison Between First-generation Tkismentioning

confidence: 99%

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A Comparison Between First-, Second- and Third-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients with Non-Small-Cell Lung Cancer and Brain Metastases

Caponnetto

Cantale²,

Friedlaender

et al. 2021

JMP

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Patients with non-small-cell lung cancer (NSCLC), harboring Epidermal Growth Factor Receptor (EGFR) mutations, are more susceptible to brain metastases (BM). Comparisons of the efficacy of different-generation EGFR-tyrosine kinase inhibitors (TKI) on BMs from NSCLC are currently limited. We identified studies comparing different EGFR-TKIs for NSCLC through Pubmed literature search and selected those with neurological outcome data. By two retrospective analyses, Erlotinib showed longer neurological time-to-progression (30 months vs. 15.8 months, P = 0.024) and reduced the risk of central nervous system (CNS) progression (Hazard Ratio (HR) 0.25; 95% CI, 0.08–0.81; P = 0.021) compared to Gefitinib. In a phase 2b randomized trial, 16% of patients with BMs had a similar Progression Free Survival (PFS) (HR 0.76, 95% CI 0.41–1.44) or Overall Survival (OS) (HR 1.16, 95% CI 0.61–2.21) with Afatinib versus Gefitinib; a lower risk of developing subsequent BMs with Afatinib than Gefitinib (HR 0.49; 95% CI 0.34–0.71; P < 0.001) was reported by a retrospective study. A randomized phase 3 trial proved that patients with BMs treated with Osimertinib had longer PFS (HR 0.47, 95% CI 0.30–0.74) and OS (HR 0.79, 95% CI 0.61–1.01) than with Gefitinib, and lower incidence of CNS progression (6% vs. 15%, respectively). Although there is limited evidence, differences in CNS activity may exist between EGFR-TKIs.

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“…Overall, 4 clinical trials [17,18] and 4 retrospective analyses [19][20][21][22][23][24][25][26][27] were reviewed (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Section: Comparison Between First-generation Tkismentioning

confidence: 99%

A Comparison Between First-, Second- and Third-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients with Non-Small-Cell Lung Cancer and Brain Metastases

Caponnetto

Cantale²,

Friedlaender

et al. 2021

JMP

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“…In recent years, the clinical effect of EGFR-TKIs in the treatment of patients with NSCLC has gradually attracted attention, and several clinical trials have proven their effectiveness (Ballard et al, 2016;Wang et al, 2017;Su et al, 2018;Saida et al, 2019;Yomo et al, 2019;Yun et al, 2019;Dai et al, 2020). A retrospective study (Liu et al, 2020) compared the efficacy of first-generation icotinib and gefitinib against EGFR-mutated NSCLC brain metastases. There was no significant difference in the intracranial overall response rate (ORR) and disease control rate between the groups.…”

Section: Discussionmentioning

confidence: 99%

Experimental Study of Almonertinib Crossing the Blood-Brain Barrier in EGFR-Mutant NSCLC Brain Metastasis and Spinal Cord Metastasis Models

Zhang

Niu

et al. 2021

Front. Pharmacol.

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Roughly one third of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)-sensitive mutated (EGFRm) tumors experience disease progression through central nervous system (CNS) metastases during treatment. Although EGFR-TKIs have been reported to be favored in some patients with EGFRm NSCLC CNS metastases, novel EGFR-TKIs with proven efficacy in CNS pathologies are clinically needed.To investigate whether almonertinib, a novel third-generation EGFR-TKI for NSCLC, can cross the blood-brain barrier (BBB) and deliver treatment for EGFR-mutant NSCLC brain metastases and spinal cord metastases, we constructed NSCLC brain metastasis and spinal cord metastasis models in vivo to observe the anti-tumor effects of almonertinib. Using ABCB1-MDCK and BCRP-MDCK monolayer cells as the in vitro study model, the effects of transport time and drug concentration on the apparent permeability coefficient of almonertinib and its active metabolite, HAS-719, were investigated. The results of this study show that almonertinib can significantly inhibit PC9 brain and spinal cord metastases. Pharmacokinetic studies in mice revealed that almonertinib has good BBB penetration ability, whereas the metabolite HAS-719 does not easily penetrate the BBB. Early clinical evidence of almonertinib activity in patients with EGFRm-advanced NSCLC and brain metastases has also been reported. In conclusion, almonertinib easily penetrates the BBB and inhibits advanced NSCLC brain and spinal cord metastases.

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“…First-generation EGFR-TKIs (gefitinib, erlotinib, and icotinib) and second-generation EGFR-TKIs (afatinib and dacomitinib) have poor BBB permeability and provide a higher ORR of approximately 60% of intracranial lesions in NSCLC CNS metastasis compared with that of WBRT with or without chemotherapy (ORR < 40%) [60][61][62][63][64]. Studies on EGFR-TKIs in patients with NSCLC CNS metastasis show that pulsed high-dose erlotinib or gefitinib can increase the drug concentration in the CSF [65,66] and effectively induce tumor cell apoptosis [67].…”

Section: Targeted Therapy With Egfr Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

Research Progress and Challenges in the Treatment of Central Nervous System Metastasis of Non-Small Cell Lung Cancer

Wang

Guo

et al. 2021

Cells

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Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors and has high morbidity and mortality rates. Central nervous system (CNS) metastasis is one of the most frequent complications in patients with NSCLC and seriously affects the quality of life (QOL) and overall survival (OS) of patients, with a median OS of untreated patients of only 1–3 months. There are various treatment methods for NSCLC CNS metastasis, including surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy, which do not meet the requirements of patients in terms of improving OS and QOL. There are still many problems in the treatment of NSCLC CNS metastasis that need to be solved urgently. This review summarizes the research progress in the treatment of NSCLC CNS metastasis to provide a reference for clinical practice.

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Icotinib is as efficacious as gefitinib for brain metastasis of EGFR mutated non-small-cell lung cancer

Cited by 11 publications

References 45 publications

A Comparison Between First-, Second- and Third-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients with Non-Small-Cell Lung Cancer and Brain Metastases

A Comparison Between First-, Second- and Third-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients with Non-Small-Cell Lung Cancer and Brain Metastases

Experimental Study of Almonertinib Crossing the Blood-Brain Barrier in EGFR-Mutant NSCLC Brain Metastasis and Spinal Cord Metastasis Models

Research Progress and Challenges in the Treatment of Central Nervous System Metastasis of Non-Small Cell Lung Cancer

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