Nivolumab for patients with recurrent glioblastoma progressing on bevacizumab: a retrospective case series

A single institution retrospective evaluation of nivolumab following disease progression on bevacizumab in adults with recurrent glioblastoma (GBM) with an objective of determining progression free survival (PFS). There is no accepted therapy for recurrent GBM after failure of bevacizumab. 16 adults, ages 52-72 years (median 62), with recurrent GBM were treated. All patients had previously been treated with surgery, concurrent radiotherapy and temozolomide, and post-radiotherapy temozolomide. Bevacizumab (with or without lomustine) was administered to all patients at first recurrence. Patients were treated with nivolumab only (3 mg/kg) once every 2 weeks at second recurrence. One cycle of nivolumab was defined as 2 treatments. Neurological evaluation was performed bi-weekly and neuroradiographic assessment every 4 weeks. A total of 37 treatment cycles (median 2) were administered of nivolumab in which there were 14 Grade 2 adverse events (AEs) and Grade 3 AEs in two patients. No Grade 4 or 5 AEs were seen. Following 1 month of nivolumab, seven patients demonstrated progressive disease and discontinued therapy. No patient demonstrated a response though nine patients demonstrated neuroradiographic stable response. Survival in the entire cohort ranged from 2 to 6 months with a median of 3.5 months (CI 2.8, 4.2). Median and 6-month PFS at 6 months was 2.0 months (range 1-5 months; CI 1.3, 2.7) and 0% respectively. Nivolumab salvage therapy demonstrated no survival advantage in patients with recurrent bevacizumab refractory GBM emphasizing a continued unmet need in neuro-oncology.