regorafenib

Regorafenib



Regorafenib (BAY 73-4506, commercial name Stivarga) is an oral multi-kinase inhibitor developed by Bayer which targets angiogenic, stromal, and oncogenic receptor tyrosine kinase (RTK). Regorafenib shows anti-angiogenic activity due to its dual-targeted VEGFR2-TIE2 tyrosine kinase inhibition. Since 2009 it was studied as a potential treatment option in multiple tumor types.

By 2015 it had 2 US approvals for advanced cancers.

Antiangiogenic treatment approaches have failed to improve outcomes in randomized trials of high-grade astrocytoma. One key mechanism of resistance to antiangiogenic treatment may concern the upregulation of alternative pro-angiogenic pathways. Regorafenib is a potent multikinase inhibitor that may alter some of those pathways.


Tzaridis T, Gepfner-Tuma I, Hirsch S, Skardelly M, Bender B, Paulsen F, Schaub C, Weller J, Schäfer N, Herrlinger U, Tabatabai G. Regorafenib in advanced high-grade glioma: a retrospective bicentric analysis. Neuro Oncol. 2019 Apr 23. pii: noz071. doi: 10.1093/neuonc/noz071. [Epub ahead of print] PubMed PMID: 31089718 1).


In a retrospective study, Kebir et al. investigated the efficacy and radiographic tumor growth patterns of regorafenib in recurrent high-grade astrocytoma.

They screened for patients with a high-grade astrocytoma in whom regorafenib was administered for at least 4 weeks. We assessed treatment efficacy in terms of progression-free survival (PFS), overall survival, and adverse events defined by Common Toxicity Criteria (CTC). In addition, radiographic tumor growth patterns were determined at baseline and recurrence.

A total of 6 patients met the eligibility criteria. The number of recurrences prior to regorafenib varied between 2 and 6. Patients were on regorafenib treatment for at least 4 weeks and maximally 14 weeks. Median PFS was 3.5 months and ranged from 2.0 to 4.0 months. Radiographic response was progressive disease in all patients with an objective response rate of 0%. CTC°3 adverse events were observed in all but one patient. The most common radiographic growth pattern was local with no change in growth pattern at recurrence. An infiltrative tumor growth was not induced in any patient.

This retrospective study indicates the very poor performance of regorafenib in recurrent high-grade astrocytoma with a fairly high number of CTC°3 adverse events. In addition, regorafenib does not seem to bear a potential for infiltrative tumor growth promotion 2).

Side effects


1)
Tzaridis T, Gepfner-Tuma I, Hirsch S, Skardelly M, Bender B, Paulsen F, Schaub C, Weller J, Schäfer N, Herrlinger U, Tabatabai G. Regorafenib in advanced high-grade glioma: a retrospective bicentric analysis. Neuro Oncol. 2019 Apr 23. pii: noz071. doi: 10.1093/neuonc/noz071. [Epub ahead of print] PubMed PMID: 31089718.
2)
Kebir S, Rauschenbach L, Radbruch A, Lazaridis L, Schmidt T, Stoppek AK, Pierscianek D, Stuschke M, Forsting M, Sure U, Keyvani K, Kleinschnitz C, Scheffler B, Glas M. Regorafenib in patients with recurrent high-grade astrocytoma. J Cancer Res Clin Oncol. 2019 Apr;145(4):1037-1042. doi: 10.1007/s00432-019-02868-5. Epub 2019 Feb 28. PubMed PMID: 30820715.
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