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. 2019 Apr;145(4):1037-1042.
doi: 10.1007/s00432-019-02868-5. Epub 2019 Feb 28.

Regorafenib in patients with recurrent high-grade astrocytoma

Sied Kebir  1   2   3   4 , Laurel Rauschenbach  3   4   5 , Alexander Radbruch  6 , Lazaros Lazaridis  1   3   4 , Teresa Schmidt  1   3   4 , Ann-Kathrin Stoppek  1   3   4 , Daniela Pierscianek  3   4   5 , Martin Stuschke  7 , Michael Forsting  6 , Ulrich Sure  3   4   5 , Kathy Keyvani  8 , Christoph Kleinschnitz  9 , Björn Scheffler  2   3   4 , Martin Glas  10   11   12   13
Affiliations

Regorafenib in patients with recurrent high-grade astrocytoma

Sied Kebir et al. J Cancer Res Clin Oncol. 2019 Apr.

Abstract

Purpose: Antiangiogenic treatment approaches have failed to improve outcome 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. In this retrospective study, we investigated efficacy and radiographic tumor growth patterns of regorafenib in recurrent high-grade astrocytoma.

Methods: We screened for patients with 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.

Results: A total of 6 patients met 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.

Conclusions: This retrospective study indicates a 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.

Keywords: Astrocytoma; Glioblastoma; High-grade glioma; Regorafenib.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
a Progression-free survival. b Waterfall plot showing the change in tumor size (as measured according to RANO criteria) at follow-up MRI (contrast-enhanced T1) compared to baseline prior to regorafenib onset. c Transition plot visualizing how tumor growth pattern changed from baseline (before regorafenib) to recurrence (while under regorafenib). Distant tumor growth was induced in one patient only. Other than that local growth pattern was the dominant with no change at recurrence. D diffuse
Fig. 2
Fig. 2
Exemplary tumor recurrence on regorafenib treatment as evidenced on MRI (contrast-enhanced T1 sequence) is shown for a patient, where tumor size increased 453% as compared to baseline
See this image and copyright information in PMC

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