Role of a second chemotherapy in recurrent malignant glioma patients who progress on bevacizumab

¹ Division of Cancer Neurology, Department of Neurology, and Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Dana-Farber/Brigham and Women's Hospital; Harvard Medical School; Boston, MA, USA
² Massachusetts General Hospital Biostatics Center, Boston, MA, USA
³ Center for Neuro-Oncology, Dana-Farber/Brigham and Women's Cancer Center, Dana-Farber/Brigham and Women's Hospital, Boston, MA, USA
⁴ Division of Cancer Neurology, Department of Neurology, Dana-Farber/Brigham and Women's Cancer Center, Dana-Farber/Brigham and Women's Hospital; Harvard Medical School; Boston, MA, USA

^* To whom correspondence should be addressed. E-mail: pwen{at}partners.org.

	Abstract

Objective: Bevacizumab is a humanized monoclonal antibody against vascular endothelial growth factor (VEGF) that has efficacy in recurrent malignant gliomas, particularly in combination with irinotecan. However, responses are rarely durable. Continuation of bevacizumab in combination with another chemotherapeutic agent may demonstrate some activity.

Methods: Retrospective review of 54 patients with recurrent malignant gliomas who progressed on a bevacizumab-containing regimen and were then treated with an alternate bevacizumab-containing regimen. All patients received bevacizumab 5-10 mg/kg IV every 2 weeks alone or in combination with an additional chemotherapeutic agent, such as irinotecan. There was no limit on the number of prior therapies. Clinical characteristics and outcomes were reviewed. Tumor progression was determined by a combination of clinical status and radiographic changes.

Results: Patient characteristics were 33 men, 21 women; median age 50 years (range 23 to 72); median KPS 80 prior to the first bevacizumab-containing regimen and 70 prior to the second regimen; median prior chemotherapy regimens including the first bevacizumab-containing regimen was 3 (range 2 to 5). Median progression-free survival (PFS) on first bevacizumab-containing regimen was 124 days (95% CI, 87 to 154). Six-month progression-free survival (6M-PFS) was 33%. Median PFS on the second bevacizumab-containing regimen was 37.5 days (95% CI, 34 to 42). 6M-PFS was 2%. 10 patients on the first regimen and 12 patients on the second regimen suffered grade 3/4 toxicities.

Conclusions: Patients with malignant gliomas who progress despite a bevacizumab-containing regimen rarely respond to a second bevacizumab-containing chemotherapeutic regimen. In these patients alternate therapies should be considered.

Key Words: High grade glioma, Bevacizumab, Malignant glioma

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