Tivozanib, a highly potent and selective inhibitor of VEGF receptor tyrosine kinases, for the treatment of metastatic renal cell carcinoma

Jacob, Allen; Shook, Jaret; Hutson, Thomas E.

doi:10.2217/fon-2020-0443

Cited by 14 publications

(10 citation statements)

References 49 publications

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“…Tivozanib (Fotivda), formerly known as AV-951 or KRN-951, is an oral, potent, selective VEGFR TKI with a weak off-target effect [ 10 ]. The inhibitory effect on VEGFRs is stronger compared to other previously used TKIs in metastatic renal-cell carcinoma (mRCC) [ 11 ]. However, tivozanib can also inhibit c-kit, which is eight times less sensitive to tivozanib compared to VEGFR 1, 2, and 3.…”

Section: Reviewmentioning

confidence: 99%

Current Status of Tivozanib in the Treatment of Patients With Advanced Renal Cell Carcinoma

Sakellakis¹,

Zakopoulou²

2023

Cureus

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The introduction of tyrosine kinase inhibitors (TKIs) against vascular endothelial growth factor receptors (VEGFRs) has transformed the therapeutic landscape for patients with advanced renal cell carcinoma (RCC). However, dose reductions and interruptions are frequently needed due to limited toxicity, mostly from offtarget effects. Tivozanib is a potent, selective VEGFR TKI with weak off-target effects. TIVO-1 and TIVO-3 were randomized controlled phase 3 trials that investigated the efficacy and safety of tivozanib versus sorafenib as initial targeted therapy and after failing two previous lines (including targeted therapy), respectively. Tivozanib did not confer any survival advantage, but it significantly increased progression-free survival, response rates, and the duration of responses with a superior safety profile. Although results from subgroup analysis need to be interpreted cautiously, tivozanib demonstrated superiority after two previous lines of VEGFR TKIs or after axitinib, another selective VEGFR inhibitor. Tivozanib also demonstrated durable activity after therapy with an immune-checkpoint inhibitor, while an ongoing study investigating the combination of tivozanib/nivolumab has shown promising preliminary results regarding efficacy and safety. In conclusion, tivozanib was recently added to our therapeutic armamentarium against advanced RCC. Ongoing rational therapeutic combinations of tivozanib will determine the optimal setting in which the maximum benefit can be derived.

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Section: Reviewmentioning

confidence: 99%

Current Status of Tivozanib in the Treatment of Patients With Advanced Renal Cell Carcinoma

Sakellakis¹,

Zakopoulou²

2023

Cureus

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“…In the KEYNOTE 426 study, the pembrolizumab–axitinib combination showed superiority over sunitinib in terms of OS, PFS, and ORR [ 17 ]. However, the follow-up of the study data presented at the ASCO Annual Meeting 2020 showed a lack of maintenance in good-risk patients in terms of PFS and OS, with no significant differences between both combination and monotherapy after 23 months [ 31 ].…”

Section: Combination Therapy Versus Tki Alone In Selected Patient Subgroupsmentioning

confidence: 99%

Combination Therapy in Renal Cell Carcinoma: the Best Choice for Every Patient?

et al. 2021

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Purpose of Review Therapeutic alternatives to treat metastatic renal cell carcinoma (mRCC) are increasing, and combination therapies, including antiangiogenic agents and tyrosine kinase/mTOR/immune checkpoint inhibitors, are identified as the gold standard driven by the results of recent clinical studies. Nevertheless, the real-world RCC population is very heterogeneous, with categories of patients not represented in the enrolled trial population who may not benefit more from these treatments. The purpose of this expert review is to assess the rationale on which tyrosine kinase alone may still be a viable first-line treatment option for some subgroups of patients with mRCC. Recent Findings The first-line treatment with tyrosine kinase inhibitor monotherapy can still be considered an effective tool for addressing selected mRCCs, as highlighted by the successful outcome in a range of subjects such as favorable-risk patients, the ones suffering from autoimmune diseases, those with pancreatic or lung metastases, or previously undergoing organ transplantation and elderly subjects. Summary Some selected categories of patients may still benefit from monotherapy with TKI, and smart sequential therapies can also be considered instead of a combination strategy. Tyrosine kinase inhibitors can also act as immune modulator agents, boosting the immune response to facilitate and potentiate the therapeutic effectiveness of subsequent immunotherapy.

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“…Herein, enzalutamide is an anti-androgen that delays the progression of advanced prostate cancer for about 8 months, [90] whereas tivozanib is an anti-angiogenic agent blocking the tumor blood supply. [91] The main goal of this study is to determine whether the combination of these two drugs is more effective in delaying the progression of disease than using enzalutamide alone. The dose of the combination study is tivozanib daily oral for 21 days followed by 7 days break and enzalutamide daily oral for 28 days.…”

Section: Progress Of Clinical Investigations Of Anti-angiogenic Agents As Mono-or Combination Therapymentioning

confidence: 99%

Recent Anti‐angiogenic Drug Discovery Efforts To Combat Cancer

et al. 2021

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The process of angiogenesis promotes tumor growth and metastatic spreading and angiogenesis inhibition has therapeutic efficacy in many preclinical models. The discovery of pathways mediating tumor angiogenesis, in particular VEGFs and their receptors, paved the way to the development of antiangiogenic drugs to translate into clinic as anti-cancer agents. However, dozens of anti-angiogenic drugs have been approved and routinely used under clinical practice. However, with the compelling preclinical evidence demonstrating anti-cancer activity, therapeutic benefits in patients remained modest. Recent progress in understanding the biology of tumor angiogenesis and their molecular mechanisms opened a new prospect for improving therapeutic strategies. An emergent approach to improve efficacy and avoid resistance is to hit multiple angiogenesis pathways and or administration in combination with other anticancer agents. In this review, we have highlighted some of the emerging aspects and discussed new antiangiogenic drug discovery in the past five years.

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Tivozanib, a highly potent and selective inhibitor of VEGF receptor tyrosine kinases, for the treatment of metastatic renal cell carcinoma

Cited by 14 publications

References 49 publications

Current Status of Tivozanib in the Treatment of Patients With Advanced Renal Cell Carcinoma

Current Status of Tivozanib in the Treatment of Patients With Advanced Renal Cell Carcinoma

Combination Therapy in Renal Cell Carcinoma: the Best Choice for Every Patient?

Recent Anti‐angiogenic Drug Discovery Efforts To Combat Cancer

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