Targeted therapy with anlotinib for patient with recurrent glioblastoma

Lv, Yajuan; Zhang, Jiandong; Liu, Fengjun; Song, Meijuan; Hou, Yong; Liang, Ning

doi:10.1097/md.0000000000015749

Cited by 17 publications

(14 citation statements)

References 29 publications

(32 reference statements)

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“…A meta-analysis showed that the combination of bevacizumab and chemotherapy in the treatment of recurrent GBM significantly improved the progression-free survival and objective response rate but did not extend the OS compared with single-agent bevacizumab [18]. In cases in which standard regimens fail for patients with relapsed GBM, targeted therapies are limited [2]. Molecular markers of GBM are needed to improve personalized diagnosis and treatment and to better understand the biology to facilitate the development of new therapies [1].…”

Section: Discussionmentioning

confidence: 99%

“…The preferred treatment for GBM is surgery, and subsequent treatment is a combination of radiotherapy and chemotherapy. For patients with recurrent GBM, targeted therapies are limited [2][3][4]. Molecular markers of GBM are needed to improve personalized diagnosis and treatment and to better understand the biology of the disease to facilitate the development of new therapies [1].…”

Section: Introductionmentioning

confidence: 99%

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Targeted Therapy with Anlotinib for a Patient with an Oncogenic FGFR3-TACC3 Fusion and Recurrent Glioblastoma

et al. 2020

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We describe a case of recurrent glioblastoma treated with anlotinib in this report. The patient was administered anlotinib 12 mg p.o. once every day (days 1-14, with a 21-day cycle) (anlotinib clinical study NCT04004975) and oral temozolomide chemotherapy 100 mg/m 2 (days 1-7, days 15-21, 28-day cycle; 12 cycles). After 2 months of therapy, the patient achieved a partial response that has been maintained for >17 months of follow-up. Molecular characterization confirmed the presence of a TERT promoter mutation, wild-type IDH1/2, an FGFR3-TACC3 fusion, and FGFR3 amplification in the patient. Anlotinib is a multitarget tyrosine kinase inhibitor that was originally designed to inhibit VEGFR2/3, FGFR1-4, PDGFRα/β, and c-Kit. Patients with TERT promoter mutations and highgrade IDH-wild-type glioma have shorter overall survival than patients with IDH-wild-type glioma without TERT promoter mutations. However, this patient had a favorable clinic outcome, and FGFR3-TACC3 fusion may be a new marker for treatment of glioma with anlotinib. The Oncologist 2020;25:1-5 KEY POINTS • This case study is believed to be the first report that FGFR3-TACC3 fusion could be a novel indication to treat recurrent glioblastoma with the drug anlotinib. • This case exhibited an exceptional response (maintained partial response >17 months) after 2-month combined therapy of anlotinib and oral temozolomide chemotherapy. • This case also underscores the importance of molecular diagnosis for clinically complex cases. Tumor tissue-based assessment of molecular biomarkers in brain tumors has been successfully translated into clinical application.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Targeted Therapy with Anlotinib for a Patient with an Oncogenic FGFR3-TACC3 Fusion and Recurrent Glioblastoma

et al. 2020

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“…Lv et al published the rst case report of the administration of 12 mg anlotinib to an rGBM patient. The patient achieved a PR after 26 days, but the tumour progressed in two months [4]. Wang et al reported a recurrent GBM patient with an FGFR-TACC3 fusion who was administered anlotinib 12 mg and temozolomide 100 mg/m 2 .…”

Section: Discussionmentioning

confidence: 99%

“…Anlotinib is a novel tyrosine kinase inhibitor that targets VEGFR1/2/3, PDGFR, FGFR1/2/3/4, c-Kit, and Ret. It has been reported to have a promising effect on tumour control in an rGBM case report [4]. However, as a salvage treatment, failure ultimately occurs.…”

Section: Introductionmentioning

confidence: 99%

Safety and Efficacy of Hypofractionated Stereotactic Radiotherapy with Anlotinib Targeted Therapy for Glioblastoma at First Recurrence: A Preliminary Report

Guan

Gong

et al. 2021

Preprint

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BackgroundThe optimal treatment for recurrent glioblastoma (rGBM) remains uncertain. Hypofractionated stereotactic radiotherapy (HSRT) and anti-vascular endothelial growth factor (VEGF) antibodies (e.g., bevacizumab) have been reported to have a promising survival benefit and acceptable toxicity in recent studies. Anlotinib is a new orally administered tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR) and c-kit. It has dual anti-angiogenic and anti-tumour growth effects. This preliminary study describes our initial experience with HSRT and anlotinib as a salvage treatment for rGBM.MethodsBetween December 2019 and June 2020, rGBM patients treated with HSRT using CyberKnife concurrently with anlotinib were retrospectively analysed. Anlotinib was prescribed at 12 mg daily during HSRT. Adjuvant anlotinib was administered at 12 mg d1-14 every 3 weeks. The primary endpoint was the objective response rate (ORR) determined by the treating investigators using the Response Assessment in Neuro-Oncology (RANO) criteria, and secondary endpoints included overall survival (OS), progression-free survival (PFS) after salvage treatment, and toxicity. Toxicity was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) 5.0.ResultsWe retrospectively reviewed five patients who received salvage HSRT and anlotinib for recurrent GBM.The median planning target volume (PTV) was 26.94 cm3 (5.53–54.41 cm3). The prescribed dose was 25.0 Gy in 5 fractions. The median number of cycles of anlotinib was 9 (4–15) cycles. The median baseline Karnofsky Performance Status (KPS) was 80 (70–90). The follow-up ranged from 4 to 10 months. The ORR was 100%. Three (60%) patients had a best outcome of a partial response (PR), and 2 (40%) achieved a complete response (CR). No patients died or had progressive disease (PD) at the last follow-up. Two patients had grade 2 hand-foot syndrome, which was relieved after dermatologic treatments, and no other grade 3 or higher toxicities were recorded.ConclusionsSalvage HSRT combined with anlotinib showed a favourable outcome and acceptable toxicity for rGBM patients in this preliminary report. A prospective phase II study (NCT04197492) is ongoing to further investigate the value of HSRT combined with anlotinib in rGBM.

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“…The same large scale study identified 9 EGFR-related pathways which can be targeted by FDA-approved drugs such as Anlotinib ( 83 , 84 ). Anlotinib main use in cancer was already established to treat aggressively, drug-resistant tumors such as glioblastoma ( 85 ); Poziotinib ( 86 – 88 ). Other available EGFR-targeting molecules include Dacomitinib ( 89 ) and cationic polyamidoamine dendrimers ( 90 ).…”

Section: Pathway-based Drug Repurposingmentioning

confidence: 99%

Pathway-Based Drug-Repurposing Schemes in Cancer: The Role of Translational Bioinformatics

Hernández‐Lemus

Martínez-García

2021

Front. Oncol.

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Cancer is a set of complex pathologies that has been recognized as a major public health problem worldwide for decades. A myriad of therapeutic strategies is indeed available. However, the wide variability in tumor physiology, response to therapy, added to multi-drug resistance poses enormous challenges in clinical oncology. The last years have witnessed a fast-paced development of novel experimental and translational approaches to therapeutics, that supplemented with computational and theoretical advances are opening promising avenues to cope with cancer defiances. At the core of these advances, there is a strong conceptual shift from gene-centric emphasis on driver mutations in specific oncogenes and tumor suppressors—let us call that the silver bullet approach to cancer therapeutics—to a systemic, semi-mechanistic approach based on pathway perturbations and global molecular and physiological regulatory patterns—we will call this the shrapnel approach. The silver bullet approach is still the best one to follow when clonal mutations in driver genes are present in the patient, and when there are targeted therapies to tackle those. Unfortunately, due to the heterogeneous nature of tumors this is not the common case. The wide molecular variability in the mutational level often is reduced to a much smaller set of pathway-based dysfunctions as evidenced by the well-known hallmarks of cancer. In such cases “shrapnel gunshots” may become more effective than “silver bullets”. Here, we will briefly present both approaches and will abound on the discussion on the state of the art of pathway-based therapeutic designs from a translational bioinformatics and computational oncology perspective. Further development of these approaches depends on building collaborative, multidisciplinary teams to resort to the expertise of clinical oncologists, oncological surgeons, and molecular oncologists, but also of cancer cell biologists and pharmacologists, as well as bioinformaticians, computational biologists and data scientists. These teams will be capable of engaging on a cycle of analyzing high-throughput experiments, mining databases, researching on clinical data, validating the findings, and improving clinical outcomes for the benefits of the oncological patients.

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Targeted therapy with anlotinib for patient with recurrent glioblastoma

Cited by 17 publications

References 29 publications

Targeted Therapy with Anlotinib for a Patient with an Oncogenic FGFR3-TACC3 Fusion and Recurrent Glioblastoma

Targeted Therapy with Anlotinib for a Patient with an Oncogenic FGFR3-TACC3 Fusion and Recurrent Glioblastoma

Safety and Efficacy of Hypofractionated Stereotactic Radiotherapy with Anlotinib Targeted Therapy for Glioblastoma at First Recurrence: A Preliminary Report

Pathway-Based Drug-Repurposing Schemes in Cancer: The Role of Translational Bioinformatics

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