Efficacy of EGFR-TKIs with or without angiogenesis inhibitors in advanced non-small-cell lung cancer: A systematic review and meta-analysis

Chen, Zhaoxin; Jia, Wei Hua; Ma, Xiaoting; Yu, Jing

doi:10.7150/jca.34957

Cited by 12 publications

(9 citation statements)

References 33 publications

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“…Previous meta-analysis studies confirmed the dual pathway inhibitors had a superior effect on progression-free survival than EGFR-TKIs alone in advanced NSCLC [21,22]. Our study provided a real-world treatment response of combination EGFR TKI and antiangiogenesis in adenocarcinoma of the lung with MPE.…”

Section: Discussionsupporting

confidence: 54%

Concurrent Blockade of Endothelial EGFR and VEGF Signaling on Malignant Associated Pleural Fluid Induced Angiogenesis: From Clinic to Bench

et al. 2021

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Malignant-associated pleural fluid (MAPF) represented an unsolved problem in advanced lung cancer. Our previous work characterized increased pleural angiogenesis in lung adenocarcinoma and the propensity of MAPF on endothelial angiogenesis. This study investigated the combined efficacy of the tyrosine kinase inhibitor (gefitinib) and bevacizumab in opposing MAPF-induced angiogenesis. In lung adenocarcinoma patients with malignant pleural effusion (MPE), Kaplan–Meier analysis revealed the benefit of cotreatment with target therapy and bevacizumab. Increased EGFR expression was observed in the pleural microvessels of patients with lung adenocarcinoma both with and without mutations in EGFR. MAPF was obtained from lung adenocarcinoma patients both wild-type and mutant EGFRs. Total and phosphorylated EGFR were upregulated in HUVEC cultured with MAPF. Treatment with gefitinib as an EGFR inhibitor suppressed MAPF-induced endothelial migration and partially attenuated endothelial proliferation in both wild-type and mutant EGFR lung adenocarcinoma. Cotreatment with gefitinib and bevacizumab produced better inhibition of MAPF-induced endothelial angiogenesis than gefitinib alone in the mutant EGFR subgroup. Protein analysis of MAPF-derived exosomes revealed abundant EGFR and p-EGFR components that implied possible transfer to endothelial cells. Concluding Kaplan–Meier analysis and in vitro studies, the results indicated that the addition of bevacizumab on gefitinib treatment could suppress MAPF-induced angiogenesis in lung adenocarcinoma patients.

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Section: Discussionsupporting

confidence: 54%

Concurrent Blockade of Endothelial EGFR and VEGF Signaling on Malignant Associated Pleural Fluid Induced Angiogenesis: From Clinic to Bench

et al. 2021

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“…Thus, our data along with the literature suggests that non-driver mutated patients have poor prognosis and even driver mutated patients would have similar prognosis if exposure to third-generation novel agents is not possible. The outcomes of EGFR-mutated NSCLC treated with first-generation tyrosine kinase inhibitors can be improved by administering either VEGF inhibitors [ 26 ] or with the addition of chemotherapy [ 10 ] or alternatively by substituting it with novel third-generation agents [ 18 ]. Moreover, the results imply that in patients with LMM, the use of agents like osimertinib is warranted.…”

Section: Resultsmentioning

confidence: 99%

Leptomeningeal metastasis from non-small cell lung cancer – a post-hoc analysis from four randomised clinical trials

Patil¹,

Noronha²,

Vallathol³

et al. 2022

ecancer

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Background Leptomeningeal metastasis (LMM) from non-small cell lung cancer (NSCLC) is often an underdiagnosed entity, has a dismal prognosis and has very limited data from low- and middle-income countries. Methods A single-centre study, which included 1148 adult patients diagnosed as NSCLC, with Eastern Oncology Cooperative Group performance status 0–2, as identified from data of four prospective randomised controlled trials. Two trials included patients who had epidermal growth factor sensitive mutations (CTRI/2015/08/006113 and CTRI/2016/08/007149) and the other two included squamous cell carcinoma (CTRI/2013/02/003422) and adenocarcinoma patients (CTRI/2014/08/00484). The key objectives were to estimate the incidence, risk factors, time to development and outcomes for LMM. Results Out of 1148 patients, 36 patients (0.031%; 95%CI: 0.022–0.043) developed leptomeningeal metastasis. In these patients, median time to development of LM was 14.92 months (interquartile range: 7.7–21.84). Among the tested factors, the presence of brain metastasis was the only statistically significant risk factor associated with the development of LMM ( p -value = 0.035). The median overall survival (OS) after the development of LM was 61 days (95%CI: 38.95–83.05). The median OS in driver mutated patients was 66 days (95% CI: 14.74–117.26) versus 51 days (95% CI: 14.5–87.5) ( p -value = 0.201) in non-driver mutated patients. Only 6 (19.4%) out of 31 epidermal growth factor receptor-mutated patients received osimertinib. Patients treated with osimertinib had a median OS of 245 days (95% CI: 215.48–274.52) versus 52 days (95% CI: 22.62–81.38) for those without ( p -value = 0.327). Conclusion The incidence of LMM is low in the Indian population. In our study, there was no single factor which impacted survival in patients who developed LMM. This suggests that the overall prognosis is poor in patients with LMM where access to newer therapeutic modalities is limited.

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“…A phase I study indicated that famitinib plus docetaxel resulted in a partial response (PR) of 23.5% (4/17), stable disease (SD) of 64.7% (11/17), and median prolonged PFS of 4.35 months in famitinib 20 mg group for NSCLC patients, with lower and more manageable grade 3/4 toxicity events 11 . Preclinical and early clinical data (phase I and II trials) have shown that first‐generation EGFR‐TKIs combined with angiogenesis inhibitors are a potential strategy for the treatment of NSCLC 12 . A phase II clinical study indicated that bevacizumab plus erlotinib resulted in a significantly prolonged PFS in patients with EGFR mutation‐positive NSCLC compared to erlotinib monotherapy, with a median PFS (16.0 months vs 9.7 months, p = 0.0015) 13 .…”

Section: Introductionmentioning

confidence: 99%

Third‐generation EGFR inhibitor HS‐10296 in combination with famitinib, a multi‐targeted tyrosine kinase inhibitor, exerts synergistic antitumor effects through enhanced inhibition of downstream signaling in EGFR‐mutant non‐small cell lung cancer cells

Zhang

Quan

et al. 2021

Thoracic Cancer

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Background As a highly heterogeneous disease, lung cancer has a multitude of cellular components and patterns of gene expression which are not dependent on a single mutation or signaling pathway. Thus, using combined drugs to treat lung cancer may be a practical strategy. Methods The combined antitumor effects of HS‐10296, a third‐generation EGFR inhibitor targeting EGFR T790M mutation, with the multitargeted tyrosine kinase inhibitor (TKI) famitinib in non‐small cell lung cancer (NSCLC) were evaluated by in vitro methods such as cell proliferation, apoptosis, angiogenesis assays, and in vivo animal efficacy studies. Results Famitinib strengthened the effects of HS‐10296 on inhibiting proliferation and inducing apoptosis of NSCLC cells, possibly by synergistic inhibition of AKT and ERK phosphorylation. Meanwhile, HS‐10296 significantly potentiated the effects of famitinib on inhibiting the proliferation and migration of HUVEC, which may be through synergistic inhibition of ERK phosphorylation in HUVEC, suggesting that HS‐10296 may improve the inhibition of angiogenesis by famitinib. Moreover, combination of HS‐10296 and famitinib exerted synergistic antitumor activity in NCI‐H1975 and PC‐9 xenograft models, and this effect may be accomplished by synergistic inhibition of phosphorylation of AKT and ERK and tumor angiogenesis in tumor tissues. Conclusions Collectively, our results indicate that HS‐10296 and famitinib exhibit significant synergistic antitumor activity, suggesting that the third‐generation EGFR inhibitor combined with VEGFR inhibitor provides a promising strategy in the treatment of EGFR‐mutant NSCLC.

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Efficacy of EGFR-TKIs with or without angiogenesis inhibitors in advanced non-small-cell lung cancer: A systematic review and meta-analysis

Cited by 12 publications

References 33 publications

Concurrent Blockade of Endothelial EGFR and VEGF Signaling on Malignant Associated Pleural Fluid Induced Angiogenesis: From Clinic to Bench

Concurrent Blockade of Endothelial EGFR and VEGF Signaling on Malignant Associated Pleural Fluid Induced Angiogenesis: From Clinic to Bench

Leptomeningeal metastasis from non-small cell lung cancer – a post-hoc analysis from four randomised clinical trials

Third‐generation EGFR inhibitor HS‐10296 in combination with famitinib, a multi‐targeted tyrosine kinase inhibitor, exerts synergistic antitumor effects through enhanced inhibition of downstream signaling in EGFR‐mutant non‐small cell lung cancer cells

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