Effect of Anlotinib as a Third-Line or Further Treatment on Overall Survival of Patients With Advanced Non–Small Cell Lung Cancer

Han, Baohui; Li, Kai; Wang, Qiming; Zhang, Li; Shi, Jianhua; Wang, Zhehai; Cheng, Ying; He, Jianxing; Shi, Yuankai; Zhao, Yupei; Yu, Hui; Zhao, Yang; Chen, Weiqiang; Luo, Yi; Wu, Lin; Wang, Xiuwen; Pirker, Robert; Kang, Nan; Jin, Fang; Dong, Jian; Li, Baolan; Sun, Yan

doi:10.1001/jamaoncol.2018.3039

Cited by 416 publications

(456 citation statements)

References 25 publications

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“…It was shown to have antitumor activity in squamous carcinoma. 10,11 Expression of VEGF-C in the primary TSCC was a strong indicator for cervical lymph node metastases. 12 In human OTSCC samples, low MMP-8 in combination with high VEGF-C was an independent predictor of poor cancer-specific survival.…”

Section: Discussionmentioning

confidence: 97%

“…Anlotinib is a novel TKI targeting the vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet‐derived growth factor receptor (PDGFR), and c‐Kit. It was shown to have antitumor activity in squamous carcinoma . Expression of VEGF‐C in the primary TSCC was a strong indicator for cervical lymph node metastases .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Satisfactory short‐term outcome after anlotinib and docetaxel chemotherapy in tongue cancer with N3 cervical lymph node metastasis: A case report

Deng

Zhong

Tan

et al. 2019

Clinical Case Reports

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Satisfactory short‐term outcome after anlotinib and docetaxel chemotherapy in tongue cancer with N3 cervical lymph node metastasis: A case report

Deng

Zhong

Tan

et al. 2019

Clinical Case Reports

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“…4,5 The ALTER-0303 trial (NCT02388919) showed anlotinib significantly improved overall survival and quality of life in advanced non-small cell lung cancer (NSCLC). 6,7 Anlotinib was approved for advanced NSCLC in the third-line or further therapy in China. This study summarizes adverse event management in the ALTER-0303 trial.…”

Section: Introductionmentioning

confidence: 99%

Management of anlotinib‐related adverse events in patients with advanced non‐small cell lung cancer: Experiences in ALTER‐0303

Zhang

Wang

et al. 2019

Thoracic Cancer

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Background Anlotinib is an oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor, fibroblast growth factor receptor, platelet‐derived growth factor receptor, and stem cell factor receptor (c‐Kit). In the phase III ALTER‐0303 trial (Clinical Trial Registry ID: NCT 02388919), anlotinib significantly improved overall survival versus placebo in advanced non‐small cell lung cancer patients who had received at least two previous chemotherapy and epidermal growth factor receptor/anaplastic lymphoma kinase targeted therapy regimens. This study summarized adverse event management in this trial. Methods Patients were randomized (2:1) to anlotinib or placebo up to progression or intolerable toxicity. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 and managed by investigators. Key strategies for preventing and managing the most common adverse events included patient education, supportive care, and dose modification. Results Between February 2015 and August 2016, 294 patients received anlotinib. A total of 170 (57.8%) patients received antihypertensive medications for hypertension, 53 (18.0%) patients received levothyroxine for hypothyroidism, 24 (8.2%) patients received fibrates for hypertriglyceridemia, 11 (3.7%) patients took cortisone cream for hand‐foot syndrome, and 38 (12.9%) patients received anti‐diarrheal medications for diarrhea. Dose reduction and drug discontinuation were required in 24 (8.16%) and 31 (10.54%) patients in the anlotinib group, respectively. Conclusion Anlotinb‐related adverse events could be controlled by patient education, prophylactic measures, early and active intervention, and dose modification.

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“…On May 9, 2018, the State Food and Drug Administration (CFDA) officially approved the third line therapy program for terminal non-small-cell carcinoma (NSCLC) patients with anlotinib hydrochloride [26,27] . Anlotinib had approved anti-tumor for several cancers, such as AMTC, MRCC, NSCLC, and ASTS [28,29].…”

Section: Discussionmentioning

confidence: 99%

“…Anlotinib had approved anti-tumor for several cancers, such as AMTC, MRCC, NSCLC, and ASTS [28,29]. Currently, most researches focus on the anti-angiogenic effect of drugs on tumor cells and the therapeutic effect on non-small cell carcinoma [9,10,26,27]. However, relevant data indicated that the effect of anlotinib on the proliferation and apoptosis of drug-resistant cells in colorectal cancer is still rarely reported.…”

Section: Discussionmentioning

confidence: 99%

Anlotinib overcomes multiple drug resistant of the colorectal cancer cells via inactivating PI3K/AKT pathway

Lan

Zhao

Shang

et al. 2019

Preprint

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Background: Anlotinib is a multi-tyrosine kinase inhibitor that has been reported to have activity against colorectal cancer. However, the functional mechanisms whereby anlotinib mediates against deadly drug-resistant colorectal cancer (CRC) has not been fully describedspecifically, the potential mechanisms that inhibit proliferation and induce apoptosis remain largely unknown. Methods:MTT assays were used to detect cell viability and calculate the resistance index. Colony formation was used to evaluate the proliferation of resistant cells. DAPI staining was used to detect cell apoptosis morphologically. Annexin V-FITC with PI staining was used to detect early and late-stage apoptosis of cells. Cell cycle distribution was determined by Flow cytometry. Transwell assays were performed to examine the ability of migration and invasion. Cyclin D1 Survivin, CDK4, Bcl-2, Bax and changes of PI3K/AKT pathway were detected by Western blotting. Compared as a single agent or combined with anlotinib or LY294002, PI3K inhibitor (LY294002) was used to verify whether it inhibited drug-resistant CRC cells by lowering PI3K/AKT. Results: HCT-8/5-FU cells showed multiple drug resistance. Drug resistance index of 5-FU, ADM and DDP were 390.27, 2.55 and 4.57, respectively. Anlotinib was shown to inhibit cell viability on HCT-8/5-FU and HCT-8 cells for 24 h and 48 h in a dosage-and time-dependent pattern. Compared with 48 h, intervened with anlotinib (0 μM, 10 μM, 20 μM and 40 μM) for 24 h, the HCT-8/5-FU cells were sensitive to anlotinib, and their sensitivity was greater than that of the parent cell line (HCT-8) at 24 h. Further, anlotinib inhibited the number of cloned cells significantly and had a significant inhibitory effect on cell cycle, mainly by blocking G1 transferring to S phase. Moreover, anlotinib could down-regulate the expression of survivin, cyclin D1, CDK4, caspase-3, Bcl-2, MMP-2, vimentin, MMP-9, and N-cadherin, while up-regulating cleaved-caspase-3, Bax and E-cadherin. Anlotinib inhibited the activity of the PI3K/AKT pathway and induced apoptosis in HCT-8/5-FU cells. Using LY294002, a specific PI3K inhibitor, our experiment found anlotinib can inhibit drug-resistant CRC cells by reducing PI3K and p-AKT activity-induce apoptosis.Conclusions: Anlotinib inhibited the proliferation , metastasis and induced apoptosis of HCT-8 / 5-FU cells ; and the mechanism could be that anlotinib overcomes multiple drug resistant of the colorectal cancer cells via inactivating PI3K/AKT pathway .

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Effect of Anlotinib as a Third-Line or Further Treatment on Overall Survival of Patients With Advanced Non–Small Cell Lung Cancer

Abstract: ClinicalTrials.gov identifier: NCT02388919.

Cited by 416 publications

References 25 publications

Satisfactory short‐term outcome after anlotinib and docetaxel chemotherapy in tongue cancer with N3 cervical lymph node metastasis: A case report

Satisfactory short‐term outcome after anlotinib and docetaxel chemotherapy in tongue cancer with N3 cervical lymph node metastasis: A case report

Management of anlotinib‐related adverse events in patients with advanced non‐small cell lung cancer: Experiences in ALTER‐0303

Anlotinib overcomes multiple drug resistant of the colorectal cancer cells via inactivating PI3K/AKT pathway

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