Multi-targeted tyrosine kinase inhibitors as third-line regimen in advanced non-small cell lung cancer: a network meta-analysis

Zhang, Zhonghan; Zhao, Yuanyuan; Lü, Fangli; Hou, Xue; Ma, Yuxiang; Luo, Fan; Zeng, Kangmei; Zhang, Yaxiong; Zhou, Ting; Yang, Yunpeng; Fang, Wenfeng; Huang, Yan; Zhang, Li; Zhao, Hongyun

doi:10.21037/atm.2019.08.51

Cited by 11 publications

(13 citation statements)

References 47 publications

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“…After excluding the effect of dose reduction on PFS, we found that the median PFS of the anlotinib group was still bordering superior to the pazopanib group; this suggests the two agents may differ in their mechanisms of action. Even though preclinical studies have shown the target spectrum of pazopanib and anlotinib are similar (including VEGFR, PDGFR, FGFR, and c-Kit), there are some differences in their efficacy on different targets (29)(30)(31). The frequency and extend of AEs documented in this study also support this idea.…”

Section: Discussionsupporting

confidence: 50%

Target therapy for metastatic alveolar soft part sarcoma: a retrospective study with 47 cases

Liu

Fan

et al. 2020

Ann Transl Med

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Background: Alveolar soft part sarcoma (ASPS) is a translocation-associated soft-tissue tumor resistant to conventional cytotoxic agents. This report aims to compare the efficacy of anlotinib versus pazopanib as targeted monotherapy in metastatic ASPS and to determine the impact of drug dosage reduction on disease control.Methods: Sixteen and 31 patients with metastatic ASPS were respectively treated with anlotinib and pazopanib monotherapy at a single institution. Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were retrieved and compared between both therapeutic arms. Adverse events (AEs) within each group were recorded. Kaplan-Meier survivorship curves computed the impact of drug dosage reduction on PFS.Results: The anlotinib group showed an ORR of 31.2%, compared to 35.5% in the pazopanib arm (P=0.772). Median PFS was 23.6 months [95% confidence interval (CI), 16.2-31.0 months] in patients treated with anlotinib, but dropped to 13.7 months (95% CI, 10.8-16.7 months) in those managed with pazopanib (P=0.023). One (6.3%) patient on anlotinib and 11 (35.5%) on pazopanib developed AEs requiring drug dosage reduction (P=0.029), which significantly reduced patients' PFS in the latter setting (10.5 vs.15.8 months, P=0.012). In patients without dosage reduction, anlotinib showed a bordering advantage than pazopanib on median PFS (24.5 vs. 15.8 months, P=0.112).Conclusions: Compared to pazopanib, anlotinib yielded longer PFS and lower incidence of AEs in ASPS patients. Drug dosage reduction was more frequently encountered with the former agent and affected the disease control.

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Section: Discussionsupporting

confidence: 50%

Target therapy for metastatic alveolar soft part sarcoma: a retrospective study with 47 cases

Liu

Fan

et al. 2020

Ann Transl Med

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“…Various studies on multitarget drugs for respiratory diseases are now in progress. Anlotinib, a relatively novel multitarget TKI for tumor angiogenesis and tumor cell proliferation, is effective as a third-line or beyond treatment for advanced NSCLC [ 64 ]. Entrectinib, another multitarget TKI of TRKA / B / C , ROS1 , and ALK , has been studied in patients with advanced or metastatic solid tumors harboring NTRK1 / 2 / 3 , ROS1 , or ALK gene fusions [ 65 ].…”

Section: Novel Compoundsmentioning

confidence: 99%

Novel Multitarget Therapies for Lung Cancer and Respiratory Disease

2020

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In recent years, multitarget drugs for neurological diseases such as Alzheimer’s disease have been developed and well researched. Many studies have revealed that multitarget drugs are also useful for lung cancer and respiratory diseases. Pemetrexed is a multitargeted antifolate with strong antitumor activity against mesothelioma and lung adenocarcinoma. Crizotinib is an ATP-competitive tyrosine kinase inhibitor that targets c-MET, ROS1, and ALK. Alectinib is known as an ALK inhibitor but also targets LTK, CHEK2, FLT3, PHKG2, and RET. Sorafenib is a tyrosine kinase inhibitor that targets RAF kinase, KIT, VEGFR, PDGFR1β, FLT3, and RET. Nintedanib is a multiple tyrosine kinase inhibitor that targets FGFR, PDGFR, and VEGFR. In this review, we summarize the mechanisms of action of multitarget therapies and report the results of the latest clinical trials.

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“…In recent years, signi cantly improved prognosis has been achieved for lung cancer patients by treatment using small molecular targeted tyrosine kinase inhibitors (TKIs) to target anaplastic lymphoma kinase (ALK), epidermal growth factor receptor (EGFR), and C-ros oncogene 1-receptor tyrosine kinase (ROS1) (1,3,(7)(8)(9)(10). Patients with BM from NSCLC receiving these treatments also showed signi cantly improved survival.…”

Section: Introductionmentioning

confidence: 99%

“…The response rate of brain lesions from NSCLC BM patients with EGFR mutation to rst generation TKIs reached 60.0% − 80.0%, with complete remission (CR) rate of 40.0% and mOS of 15-20 months (11). A meta-analysis study also showed that the rst generation TKIs had signi cant effect on BM in patients with EGFR/ALK gene mutations, with median progression free survival (mPFS) of 7.4 months and mOS of 11.9 months (7,12). Compared with rst generation TKIs, second generation TKIs such as afatinib can simultaneously inhibit several ErbB family members (including EGFR, ErbB3, ErbB4, and human epidermal growth factor receptor-2) (13).…”

Section: Introductionmentioning

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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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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Multi-targeted tyrosine kinase inhibitors as third-line regimen in advanced non-small cell lung cancer: a network meta-analysis

Cited by 11 publications

References 47 publications

Target therapy for metastatic alveolar soft part sarcoma: a retrospective study with 47 cases

Target therapy for metastatic alveolar soft part sarcoma: a retrospective study with 47 cases

Novel Multitarget Therapies for Lung Cancer and Respiratory Disease

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

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