Progression-free and overall survival in patients with recurrent Glioblastoma multiforme treated with last-line bevacizumab versus bevacizumab/lomustine

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Progression-free and overall survival in patients with recurrent Glioblastoma multiforme treated with last-line bevacizumab versus bevacizumab/lomustine D. H. Heiland1 • W. Masalha1 • P. Franco1 • M. R. Machein1 • A. Weyerbrock1 Received: 17 June 2015 / Accepted: 19 November 2015 / Published online: 27 November 2015 Springer Science+Business Media New York 2015 Abstract Bevacizumab (BEV) is widely used for treatment of patients with recurrent glioblastoma multiforme (GBM). 1-(2-Chlorethyl)-cyclohexyl-nitrosourea (CCNU, lomustine) monotherapy is an approved chemotherapeutical option for recurrent GBM. Recent evidence demonstrated a survival benefit of combined treatment with BEV and CCNU in patients with a first recurrence of GBM. We examined the outcome of recurrent GBM patients with BEV monotherapy versus BEV/CCNU therapy when used as last-line therapy. 35 patients with recurrent GBM treated between 2010 and 2014 were included in this retrospective study. Progression-free and overall survival was determined with reference to the beginning of BEV or BEV/ CCNU therapy and initial diagnosis. 17 patients received BEV monotherapy, 18 patients received combined BEV and CCNU therapy. The impact of parameters such as IDH mutation, MGMT promoter methylation, tumor localization, histology and the number of surgeries were included in a multivariate ANOVA analysis. Furthermore, Karnofsky performance score (KPS), neurological function and toxicity were assessed. BEV/CCNU treatment led to an extension of PFS (6.11 months; 95 % CL 3.41–12.98 months; log-rank p = 0.00241) and OS (6.59 months; 95 % CL 5.51–16.3 months; log-rank p = 0.0238) of 2 months compared to BEV monotherapy. This survival advantage was independent of histology, IDH mutation status or the number of previous surgeries. Neurological function, KPS and toxicity were not significantly different between both treatment groups. Last-line therapy with BEV/CCNU results in a longer PFS and OS compared to BEV monotherapy and is well-tolerated. These findings confirm the role of these agents in the treatment of recurrent GBM and are in line with other studies. Keywords Glioblastoma multiforme Bevacizumab CCNU Tumor recurrence Last-line therapy Introduction Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults with an incidence of 3–4 cases per 100.000 people [9]. In spite of the best available treatment, the prognosis for patients with recurrent GBM is poor, with a median survival of 25–40 weeks [6, 11, 12, 25, 28]. Previous studies have identified genetic aberrations in glioblastomas that are used to classify tumors into different subgroups according to their molecular signature [4, 18, 19, 27] with the purpose of finding new targets for personalized therapy. Despite of this, no breakthrough treatment options have been developed to improve the medical management of glioblastoma so far [30].The firstline therapy of GBM is the surgical resection followed by adjuvant chemoradiation with temozolomide (TMZ) as described by Stupp et al. [23]. In the case of recurrent GBM, several therapeutic options are depicted in the literature, although no consensus has been reached. The most common treatment strategies for recurrent GBM include dose-escalation regimens of TMZ [29]. Similar to TMZ therapy, CCNU (Lomustine), an alkylating nitrosurea drug, can be administered at initial diagnosis or at tumor recurrence. In a meta-analysis including 12 studies of a nitrosurea-containing regimen, however, did not demonstrate a survival benefit as a monotherapy or combined with TMZ [22]