Rebound tumour progression after the cessation of bevacizumab therapy in patients with recurrent high-grade glioma

Abstract

After withdrawal of bevacizumab in patients with recurrent high-grade glioma, we have observed a rapid tumour re-growth or "rebound" radiographic phenomenon with accelerated clinical decline. We retrospectively reviewed 11 patients treated at the Henry Ford Hermelin Brain Tumor Center with recurrent high-grade glioma who demonstrated a rebound progression pattern after the discontinuation of bevacizumab. The original tumour area-of-enhancement increased by a mean of 158%, when compared to the rebound magnetic resonance imaging. After rebound, no patients (0/8) showed a response to next-line treatments that did not include bevacizumab. The median survival of those re-treated with bevacizumab was 149 and 32 days for those who received other regimens. Abrupt discontinuation of bevacizumab after recurrence often leads to a dramatic rebound phenomenon and rapid clinical decline. Slow tapering of the bevacizumab dose after tumour progression may prevent this from occurring and improve responsiveness to next-line therapies.

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“…It could act by sequestering VEGF-A in the blood and/or tumor interstitium or induce normalization of VEGF-A concentration in these compartments (14). Despite initial efficacy, the withdrawal of bevacizumab can be associated to rapid tumor regrowth or a "rebound" phenomenon with accelerated clinical decline in patients (15,16). Moreover, in case of tumor progression under bevacizumab, salvage chemotherapy has been quite inefficient, suggesting the emergence of a treatment-resistant phenotype (17).…”

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“…Another interesting observation is the acceleration of tumor progression after discontinuation bevacizumab due to resistance in some tumors, supporting the notion that an agent can be beneficial even after the anatomical progression (Zuniga et al, 2010), (Cacheux et al, 2008).…”

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“…The second is accelerated tumor progression after cessation of the anti-VEGF, bevacizumab in particular, which is endorsed by several preclinical and observational studies. 9,10,14 The third issue is evidence supporting the continuation of bevacizumab beyond progression in the second-line. 13 Therefore, defining a particular group of patients who can safely discontinue bevacizumab after proven tumor response is necessary and may help to solve these issues.…”