Phase II study of anlotinib for treatment of advanced soft tissues sarcomas.

Chi, Yihebali; Sun, Yongkun; Cai, Jianqiang; Yao, Yang; Hong, Xin; Fang, Zhiwei; Sun, Ping; Wang, Guowen; Wu, Qiong; Qu, Guofan; Wang, Shusen; Song, Jin-Xin; Yu, Jianchun; Lu, Yuefeng; Zhu, Xiaoyang; Niu, Xiaohui; Zhou, He

doi:10.1200/jco.2016.34.15_suppl.11005

Cited by 20 publications

(18 citation statements)

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“…The progression-free rate at 12 weeks was 57.23%, median PFS was 5.63 months, and ORR was 11.45%. The drug showed a particular activity in patients with ASPS; the progression-free rate at 12 weeks was 76.92% in this group, similarly as in the case of sunitinib [26].…”

Section: Anlotinibsupporting

confidence: 58%

Advances in systemic treatment of advanced soft tissue sarcomas

Dudzisz-Śledź

Rogala

2019

Oncol Clin Pract

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Systemic treatment in soft tissue sarcoma (STS) is an important element of therapy in a disease eligible for combined treatment with a radical intention and is the basis for the treatment of an unresectable or metastatic disease. The possibilities of treating STS are limited and for many years progress in this area was minor and the main drugs used in this indication were and still remain anthracyclines and alkylating agents. Clinical trials with new drugs are difficult for STS due to the heterogeneity of these tumours and due to their rare occurrence. Over the past two decades, there have been tested many substances in this indication, including molecularly targeted drugs. Great success was imatinib in the treatment of gastrointestinal stromal tumours (GIST). Other drugs in STS have been tested and approved for use, e.g. sunitinib and regorafenib in the treatment of GIST, pazopanib in the treatment of non-GIST STS, trabectedin and olaratumab in the treatment of STS. First reports on the effectiveness of immunotherapy in the treatment of rare subtypes of STS are also available.

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Section: Anlotinibsupporting

confidence: 58%

Advances in systemic treatment of advanced soft tissue sarcomas

Dudzisz-Śledź

Rogala

2019

Oncol Clin Pract

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“…Considering that anlotinib induced tumors to shrink in soft tissue sarcomas in a phase I study, a multicenter, single-arm, phase II study subsequently explored anlotinib activity in patients with advanced STS who had failed previous conventional treatments [ 42 ]. The enrolled patients had malignant fibrous histiocytoma (MFH), liposarcoma, leiomyosarcoma (LMS), synovial sarcoma (SS), or other sarcomas, but not rhabdomyosarcoma (RMS), chondrosarcoma, or GIST STS.…”

Section: Therapeutic Efficacy Of Anlotinibmentioning

confidence: 99%

Anlotinib: a novel multi-targeting tyrosine kinase inhibitor in clinical development

et al. 2018

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Anlotinib is a new, orally administered tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptors (PDGFR), and c-kit. Compared to the effect of placebo, it improved both progression-free survival (PFS) and overall survival (OS) in a phase III trial in patients with advanced non-small-cell lung cancer (NSCLC), despite progression of the cancer after two lines of prior treatments. Recently, the China Food and Drug Administration (CFDA) approved single agent anlotinib as a third-line treatment for patients with advanced NSCLC. Moreover, a randomized phase IIB trial demonstrated that anlotinib significantly prolonged the median PFS in patients with advanced soft tissue sarcoma (STS). Anlotinib also showed promising efficacy in patients with advanced medullary thyroid carcinoma and metastatic renal cell carcinoma (mRCC). The tolerability profile of anlotinib is similar to that of other tyrosine kinase inhibitors that target VEGFR and other tyrosine kinase-mediated pathways; however, anlotinib has a significantly lower incidence of grade 3 or higher side effects compared to that of sunitinib. We review the rationale, clinical evidence, and future perspectives of anlotinib for the treatment of multiple cancers.

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“…Anlotinib is approved by CFDA for indication of NSCLC in 2018. One ongoing phase II trial suggested that anlotinib is also highly active against a broad spectrum of soft tissue sarcomas . In our study, we performed preclinical experiments demonstrating the therapeutic effects of anlotinib at the cellular level and in animal models to show that anlotinib may be a candidate targeted drug for patients with advanced osteosarcoma.…”

Section: Introductionmentioning

confidence: 99%

“…One ongoing phase II trial suggested that anlotinib is also highly active against a broad spectrum of soft tissue sarcomas. 21 In our study, we performed preclinical experiments demonstrating the therapeutic effects of anlotinib at the cellular level and in animal models to show that anlotinib may be a candidate targeted drug for patients with advanced osteosarcoma. Additionally, we identified the molecular mechanism through which anlotinib exerts its effects, a topic that should be investigated further in upcoming clinical trials of therapies for osteosarcoma.…”

Section: Introductionmentioning

confidence: 99%

Anlotinib, a novel small molecular tyrosine kinase inhibitor, suppresses growth and metastasis via dual blockade of VEGFR2 and MET in osteosarcoma

Wang

Sun

Jiang

et al. 2019

Intl Journal of Cancer

105

108

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Osteosarcoma is the most common primary malignant bone tumor in children and adolescents, with highly aggressive behavior and early systemic metastasis. The survival rates for osteosarcoma remain unchanged over the past two decades. Studies aiming to find new or alternative therapies for patients with refractory osteosarcoma are urgently needed. Anlotinib, a novel multi‐targeted tyrosine kinase inhibitor (TKI), has exhibited encouraging clinical activity in NSLCC and soft tissue sarcoma, whereas its effect on osteosarcoma has not been studied. In our study, we investigated the anti‐tumor activity and underlying mechanism of anlotinib in osteosarcoma. Various in vitro and in vivo models of human osteosarcoma were used to determine the anti‐proliferative, anti‐angiogenesis and anti‐metastasis efficacy of anlotinib. Our results showed that anlotinib suppressed tumor growth and increased the chemo‐sensitivity of osteosarcoma. In addition, anlotinib inhibited migration and invasion in osteosarcoma cells. Furthermore, in order to explore the anti‐tumor mechanism of anlotinib, phospho‐RTK antibody arrays were performed. These analyses confirmed that anlotinib suppressed the phosphorylation of MET, VEGFR2 and the downstream signaling pathway activation. Moreover, we demonstrated that anlotinib blocked hepatocyte growth factor (HGF)‐induced cell migration, invasion and VEGF‐induced angiogenesis. Notably, a 143B‐Luc orthotopic osteosarcoma model further showed that anlotinib significantly inhibited growth and lung metastasis of implanted tumor cells. Our preclinical work indicates that anlotinib acts as a novel inhibitor of VEGFR2 and MET that blocks tumorigenesis in osteosarcoma, which could be translated into future clinical trials.

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Phase II study of anlotinib for treatment of advanced soft tissues sarcomas.

Cited by 20 publications

References 0 publications

Advances in systemic treatment of advanced soft tissue sarcomas

Advances in systemic treatment of advanced soft tissue sarcomas

Anlotinib: a novel multi-targeting tyrosine kinase inhibitor in clinical development

Anlotinib, a novel small molecular tyrosine kinase inhibitor, suppresses growth and metastasis via dual blockade of VEGFR2 and MET in osteosarcoma

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