&lt;p&gt;Lenvatinib, a molecule with versatile application: from preclinical evidence to future development in anti-cancer treatment&lt;/p&gt;

Capozzi, Monica; Divitiis, Chiara De; Ottaiano, Alessandro; Arx, Claudia von; Scala, Stefania; Tatangelo, Fabiana; Delrio, Paolo; Tafuto, Salvatore

doi:10.2147/cmar.s188316

Cited by 91 publications

(65 citation statements)

References 59 publications

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“… 20 In point of fact, the possible synergistic effect of the LEN/PEM combination might alternatively be in part due to the effect of LEN on the tumor microenvironment. 12 21–23 Interestingly, LEN/PEM combination therapy has demonstrated promising antitumor activity in multiple cancers, including endometrial carcinoma 9 and renal cell carcinoma. 11 …”

Section: Discussionmentioning

confidence: 99%

“… 8–11 In particular, the MKI lenvatinib (LEN), which inhibits Vascular Endothelial Growth Factor Receptor 1-3 (VEGFR 1–3), Fibroblast Growth Factor Receptor 1-4 (FGFR 1–4), Platellet Derived Growth Factor Receptor-α (PDGFR-α), RET, and KIT, has been combined with the anti-PD-1 monoclonal antibody pembrolizumab (PEM) in phase I/II trials. Synergy between LEN and PEM is putatively due to LEN creating a more therapeutically advantageous tumor-immune microenvironment, 12 in part through blockade of immunosuppressive VEGFR signaling. This combination was approved by the United States Food and Drug Administration (FDA) for advanced endometrial carcinoma in 2019, 9 and is currently being studied as a salvage therapy for thyroid cancer, 10 renal cell carcinoma, 11 head and neck cancer, and other solid tumors.…”

Section: Introductionmentioning

confidence: 99%

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Combined lenvatinib and pembrolizumab as salvage therapy in advanced adrenal cortical carcinoma

Bedrose

Miller

Altameemi

et al. 2020

J Immunother Cancer

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BackgroundThere is no effective systemic therapy for metastatic adrenal cortical carcinoma (ACC) after failure of platinum-based chemotherapy. The efficacies of single-agent oral multikinase inhibitors (MKIs) or salvage immune checkpoint inhibitors (CPIs) have been very limited. It is unknown whether combining CPIs, such as pembrolizumab (PEM), with other therapies, such as MKIs, could yield higher response rates in ACC, yet this combination has shown promise in other cancers. Herein, we describe the first case series using PEM in combination with the MKI lenvatinib (LEN) in patients with progressive, metastatic ACC.MethodsA retrospective case series describing the use of LEN/PEM as salvage therapy in patients with progressive/metastatic ACC.ResultsEight patients were treated with the LEN/PEM combination therapy. Half were female, and the median age at time of diagnosis was 38 years (range 21–49). Three (37.5%) patients had hormonally active ACC. The median number of prior lines of systemic therapy was 4 (range 2–9). Six (75%) patients had had disease progression on prior CPIs and five (62.5%) patients had progressed on prior MKI therapy. The median progression-free survival was 5.5 months (95% CI 1.8–not reached) and median duration of therapy was 8.5 months (range 2–22). Two (25%) patients had a partial response, one (12.5%) patient had stable disease, and five (62.5%) patients had progressive disease. None of the eight patients stopped therapy because of adverse events.ConclusionsIn our small cohort of heavily pretreated patients with ACC, the combination of LEN/PEM was associated with objective responses in a subset of patients without significant toxicity. This combination should be formally investigated in phase II clinical trial with robust correlative studies to identify predictors for response.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Combined lenvatinib and pembrolizumab as salvage therapy in advanced adrenal cortical carcinoma

Bedrose

Miller

Altameemi

et al. 2020

J Immunother Cancer

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“…It inhibits VEGF receptor family 1-3, FGFR family 1-4, PDGFRa, TK receptor and RET. As a result, it may modulate the tumour microenvironment and anti-tumour responses [ 39 ]. Thalidomide An anti-angiogenic agent.…”

Section: Discussionmentioning

confidence: 99%

A systematic review of ongoing clinical trials in optic pathway gliomas

et al. 2020

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Introduction Optic pathway gliomas (OPGs), also known as Visual Pathway Gliomas, are insidious, debilitating tumours. They are most commonly WHO grade 1 pilocytic astrocytomas and frequently occur in patients with neurofibromatosis type 1. The location of OPGs within the optic pathway typically precludes complete resection or optimal radiation dosing, hence outcomes remain poor compared to many other low-grade gliomas. The aim of this systematic review was to formulate a comprehensive list of all current ongoing clinical trials that are specifically looking at clinical care of OPGs in order to identify trends in current research and provide an overview to guide future research efforts. Methods This systematic review was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The Cochrane Controlled Register of Trials (CENTRAL) and ClinicalTrials.gov were searched. Inclusion and exclusion criteria were applied and final results were reviewed. Results 501 clinical trials were identified with the search strategy. All were screened and eligible studies extracted and reviewed. This yielded 36 ongoing clinical trials, 27 of which were pharmacological agents in phase I-III. The remaining trials were a mixture of biological agents, radiation optimisation, diagnostic imaging, surgical intervention, and a social function analysis. Conclusion OPG is a complex multifaceted disease, and advances in care require ongoing research efforts across a spectrum of different research fields. This review provides an update on the current state of research in OPG and summarises ongoing trials.

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“…Lenvatinib is another oral small molecule multikinase inhibitor that selectively inhibits tyrosine kinases (e.g., VEGFR1, VEGFR2, VEGFR3), fibroblast growth factor receptor (FGFR1, FGFR2, FGFR3, FGFR4), PDGFR2, FGF and RET to suppress tumor angiogenesis and growth [10]. Lenvatinib has been certified to invoke strong antiangiogenic and anticancer effects and has been approved for the treatment of differentiated thyroid carcinoma [11].…”

Section: First-line Systemic Therapymentioning

confidence: 99%

Molecular targeted and immune checkpoint therapy for advanced hepatocellular carcinoma

Liu

Lin

Zhang

et al. 2019

J Exp Clin Cancer Res

167

132

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Molecular targeted therapy for advanced hepatocellular carcinoma (HCC) has changed markedly. Although sorafenib was used in clinical practice as the first molecular targeted agent in 2007, the SHARPE and Asian-Pacific trials demonstrated that sorafenib only improved overall survival (OS) by approximately 3 months in patients with advanced HCC compared with placebo. Molecular targeted agents were developed during the 10-year period from 2007 to 2016, but every test of these agents from phase II or phase III clinical trial failed due to a low response rate and high toxicity. In the 2 years after, 2017 through 2018, four successful novel drugs emerged from clinical trials for clinical use. As recommended by updated Barcelona Clinical Liver cancer (BCLC) treatment algorithms, lenvatinib is now feasible as an alternative to sorafenib as a first-line treatment for advanced HCC. Regorafenib, cabozantinib, and ramucirumab are appropriate supplements for sorafenib as second-line treatment for patients with advanced HCC who are resistant, show progression or do not tolerate sorafenib. In addition, with promising outcomes in phase II trials, immune PD-1/PD-L1 checkpoint inhibitors nivolumab and pembrolizumab have been applied for HCC treatment. Despite phase III trials for nivolumab and pembrolizumab, the primary endpoints of improved OS were not statistically significant, immune PD-1/PD-L1 checkpoint therapy remains to be further investigated. This review summarizes the development and progression of molecular targeted and immune-based checkpoint therapies in HCC.

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<p>Lenvatinib, a molecule with versatile application: from preclinical evidence to future development in anti-cancer treatment</p>

Cited by 91 publications

References 59 publications

Combined lenvatinib and pembrolizumab as salvage therapy in advanced adrenal cortical carcinoma

Combined lenvatinib and pembrolizumab as salvage therapy in advanced adrenal cortical carcinoma

A systematic review of ongoing clinical trials in optic pathway gliomas

Molecular targeted and immune checkpoint therapy for advanced hepatocellular carcinoma

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