Role of anlotinib-induced CCL2 decrease in anti-angiogenesis and response prediction for nonsmall cell lung cancer therapy

Lü, Jun; Zhong, Hua; Chu, Tianqing; Zhang, Xueyan; Li, Rong; Sun, Jiayuan; Zhong, Runbo; Yang, Yuqin; Alam, Mohammad Shah; Lou, Yu‐Qing; Xu, Jianlin; Zhang, Yanwei; Wu, Jun; Li, Xiaowei; Zhao, Xiaodong; Li, Kai; Lu, Liming; Han, Baohui

doi:10.1183/13993003.01562-2018

Cited by 72 publications

(63 citation statements)

References 36 publications

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“…There were some studies con rmed that the expression level of VEGF in tumor is negatively related to poor prognosis (41). As a new type of small molecule and multitargeting TKI, anlotinib mainly acts through the VEGF pathway to exert an anti-tumor role (39,42). In 2020, oncologists from the European Cancer Research Institute suggested that anlotinib has intracranial activity and could control intracranial tumors.…”

Section: Discussionmentioning

confidence: 99%

“…CRT can increase the permeability of the BBB, and increase drug concentration in the central nervous system (33). Anlotinib normalizes the blood vessels in a metastatic tumor, improves the internal microenvironment of the tumor, restores the normal permeability of the blood vessels, and plays a synergistic role with CRT to enhance radiosensitivity and reduce brain edema (8,(41)(42)(43)(44). However, further work is required to determine whether the combination of anlotinib and CRT is better than CRT alone for patients with BM from lung cancer who failed to respond to multi-line chemotherapy or were resistant to treatment with EGFR/ALK-TKIs.…”

Section: Discussionmentioning

confidence: 99%

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Therapeutic effect of cranial radiotherapy with or without anlotinib treatment for lung cancer patients with brain metastasis and non-EGFR/ALK-TKIs indication

Liu

et al. 2020

Preprint

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Background: Cranial radiotherapy (CRT) is the main treatment for lung malignant tumor with brain metastasis (BM) and lacking EGFR/ALK-TKIs indication. For non-small cell lung cancer with BM, anlotinib can improve progression free survival (PFS). We retrospectively analyzed the clinical effects of anlotinib + CRT versus CRT alone.Methods: In patients with lung cancer (adenocarcinoma, squamous carcinoma, or small cell carcinoma) with BM and non-EGFR/ALK-TKIs indication, the overall survival (OS) and PFS of anlotinib + CRT treatment versus CRT treatment alone were separately calculated and compared. The Cox proportional hazards model was used to analyze the independent prognostic factors for intracranial PFS (iPFS) and OS. All confounding factors were adjusted, including age, gender, Karnofsky Performance Status (KPS) score, smoking history, physiological characteristics, T/N stage, histology, metastases, and pathological characteristics. Subgroup analysis for iPFS and OS was performed to assess the effects on BM of treatment pattern.Results: The study included 100 patients with BM at baseline and the follow-up data. Of the 100 patients, 67 patients received CRT treatment alone and 33 patients received CRT + anlotinib treatment. The overall response rates of the CRT + anlotinib group and the CRT alone group were 90.91% and 83.58%, respectively. There was significantly more iPFS in the CRT + anlotinib group compared to CRT alone (median iPFS [miPFS]: 9.0 vs 3.0 months; hazard ratio [HR] 1.59; 95% confidence interval [CI] 1.01-2.52; p = 0.038). The OS, extracranial PFS (ePFS), and systematic PFS (sPFS) of CRT + anlotinib group were longer than those of the CRT alone group, but there was no significant statistical difference (median OS [mOS]: 9.0 vs 7.0 months, HR 1.17, 95% CI 0.74-1.85; median ePFS [mePFS]: 9.0 vs 7.0 months, HR 1.23, 95% CI 0.72-2.11; median sPFS [msPFS]: 7.0 vs 4.0 months, HR 1.37, 95% CI 0.82-2.30). The Cox proportional hazards model analysis revealed that age was an independent prognostic factor of iPFS (HR 1.65, 95% CI 1.05-2.59, p = 0.03). Age (HR 1.74, 95% CI 1.09-2.77, p = 0.02) and KPS score (HR 1.88, 95% CI 1.17-3.01, p = 0.01) were identified as independent prognostic factors of OS. Further subgroup analysis of iPFS showed that when the number of BM in the CRT + anlotinib group was less than or equal to three lesions (≤ 3), the miPFS (12.0 months) was significantly longer than that for CRT alone (> 3) (3.0 months), for CRT alone (≤ 3) (3.0 months), and for CRT + anlotinib (> 3) (7.0 months) (p = 0.014). The OS of the CRT + anlotinib group (≤ 3) (mOS 37.0 months) was much longer than that in CRT alone (> 3) (mOS 6.0 months), CRT alone (≤ 3) (mOS 7.5 months), and CRT + anlotinib (> 3) (mOS 8.5 months) groups, but this difference was not statistically significant (p = 0.051).Conclusion: Anlotinib can improve the survival of patients with lung cancer BM, with better efficacy of a combined treatment of anlotinib + CRT compared to that of CRT alone, especially for the iPFS of patients with BM ≤ 3.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Therapeutic effect of cranial radiotherapy with or without anlotinib treatment for lung cancer patients with brain metastasis and non-EGFR/ALK-TKIs indication

Liu

et al. 2020

Preprint

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“…Anlotinib-induced inhibition of angiogenesis and proliferative signaling contributed to the phenomenon [6,7]. Molecular mechanism study suggested the targets of anlotinib include CCL2 signaling pathway, receptor tyrosine kinases vascular endothelial growth (VEGFR) signaling pathway, endothelial growth factor receptor (EGFR) signaling pathway, broblast growth factor receptor (FGFR) signaling pathway, and so on [8,9]. The characteristics of this multi-target tyrosine kinase inhibitor (TKI) make a great di cult for clinical biomarker screening.…”

Section: Introductionmentioning

confidence: 99%

Plasma Proteomics Analysis for Screening Anlotinib Responders in Non-small Cell Lung Cancer

Lü¹,

Zhang²,

Zhang³

et al. 2020

Preprint

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Background Anlotinib has been demonstrated to be effective in advanced non-small cell lung cancer (NSCLC) patients. The underlying value of proteomics for anlotinib study remains unclear. Methods In this study, plasma samples from 28 anlotinib-treated NSCLC patients (including 14 responders and 14 non-responders) were performed proteomics analysis. LC-MS/MS analysis was performed on those samples with different time points including baseline, best response and progression disease. Bioinformatics analysis was performed to understand the underlying value of those differential proteins. Results Proteomics analysis suggested the differential proteins from responders after anlotinib administration potential play a role in the molecular mechanism characterization and biomarker screening. The differential proteins between responders and non-responders at baseline mainly contribute to biomarker screening. Integrative analysis indicated 43 proteins could be used as underlying biomarkers for clinical practice. Lastly, we selected ARHGDIB and demonstrated that it has potential predictive value for anlotinib. Conclusions This study not only offered the first insight that the proteomic technology potentially be used for anlotinib molecular mechanism characterization, but also provided a basis for anlotinb biomarker screening via proteomics in the future.

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“…One study showed that anlotinib could induce protective autophagy, related to anti-angiogenic property of multikinase inhibitor anlotinib (6). Lu et al (7) believe that anlotinib-induced serum CCL2 level decreases were associated with the benefits of PFS and OS in refractory advanced NSCLC patients.…”

Section: Introductionmentioning

confidence: 99%

Bronchopleural fistula in squamous cell lung cancer following anlotinib treatment: A case report

Wei

et al. 2019

mol clin onc

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Anlotinib is a multi-target tyrosine kinase inhibitor and has been approved for the treatment of patients with advanced non-small cell lung cancer. The most common adverse events of this treatment include hypertension, fatigue, thyroid-stimulating hormone elevation, hypertriglyceridemia, hand-foot syndrome and hypercholesterolemia. The present study reported the case of a 69-year-old man with squamous cell lung cancer that experienced disease progression following first-line and second-line chemotherapy. Subsequently, anlotinib was administered as a third-line therapy. Following the second cycle of oral targeted therapy, the patient was admitted to the hospital with a one-week history of chest tightnesss, shortness of breath and cough bloodstained sputum and necrosis. Computed tomography scan showed: Bronchopleural fistula (BPF) complicating lung cancer. However, symptoms were not relieved following anti-infective treatment and the patient subsequently died of respiratory failure. To the best of our knowledge, this is the first case of bronchopleural fistula associated with the use of anlotinib in a patient with squamous cell lung cancer.

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Role of anlotinib-induced CCL2 decrease in anti-angiogenesis and response prediction for nonsmall cell lung cancer therapy

Abstract: The underlying molecular mechanisms and predictive biomarkers of anlotinib benefitting NSCLC patients are still unclear. In this study, anlotinib-induced CCL2 decrease contributes to a novel insight for its anti-angiogenesis mechanism and responsive prediction.

Cited by 72 publications

References 36 publications

Therapeutic effect of cranial radiotherapy with or without anlotinib treatment for lung cancer patients with brain metastasis and non-EGFR/ALK-TKIs indication

Therapeutic effect of cranial radiotherapy with or without anlotinib treatment for lung cancer patients with brain metastasis and non-EGFR/ALK-TKIs indication

Plasma Proteomics Analysis for Screening Anlotinib Responders in Non-small Cell Lung Cancer

Bronchopleural fistula in squamous cell lung cancer following anlotinib treatment: A case report

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