Patients with Glioblastoma multiforme (GBM) have a poor prognosis and therapeutic options are scarce after recurrence. Bevacizumab (Bv) is approved for use in this setting with proven benefits in progression-free survival (PFS) but not in overall survival (OS). Arterial hypertension (HT), a well described side effect of Bv, has been proposed as a predictive marker of clinical response in GBM as well as in other neoplasms, though conflicting data is available. This study tried to evaluate the prognostic impact of HT and other factors in recurrent GBM.
Retrospective cohort of adult patients with recurrent GBM treated with a combination of Bv + Irinotecan (BvI) or Lomustine (BvL) between 01/01/2009 and 31/12/2017. Clinical records were analysed. Bv-induced HT was defined as a single evaluation ≥140/90 mmHg during first 3 months of treatment or the need to initiate or increase dose of antihypertensive drugs. OS and PFS were estimated by Kaplan-Meier method and multivariate analysis according to Cox regression; a significant level of 0.05 was chosen to assess the statistical significance.
120 patients were included with male gender predominance (64.2%) and a median age at Bv onsent of 58.7 (27-78 yo). All patients were treated in first line with surgery (complete resection: 61.7%; partial resection: 38.3%) and Stupp protocol. BvI was used in 70.8% (n = 85) and BvL in 29.2% (n = 35) patients. Bv-induced HT was found in 29% of patients (n = 29) and proteinuria (PU) in 15% (n = 18). Median PFS was 4.4 months (mo) (CI 95% 3.5-5.4) and median OS was 7.8 mo (CI 95% 6.8-87). In multivariate analysis (Table), both HT and PU had an impact in PFS. OS was significantly prolonged in patients with HT and in those without corticosteroids (CCS) at Bv.Table: 389P
|PFS (mo)||HR (CI 95%)||OS (mo)||HR (CI 95%)|
|HT||Yes||9.1||HR 1.825 (1.136-2.931), p = 0.013||14||HR 2.726 (1.325-5.608), p = 0.006|
|PU||Yes||6.1||HR 2.341 (1.282-4.275), p = 0.006||-||-|
|CCS at Bv onset||Yes||-||-||6.9||HR 2.022 (1.059-3.860), p = 0.033|
In recurrent GBM patients treated with Bv combinations, HT was significantly related with prolonged PFS and OS. PU and the need for CCS also showed a significant prognostic impact.
Clinical trial identification
Legal entity responsible for the study
Serviço de Oncologia Médica - Centro Hospitalar de São João, EPE.
Has not received any funding.
All authors have declared no conflicts of interest.