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- Title
Clinical activity and safety of atezolizumab in patients with recurrent glioblastoma.
- Authors
Lukas, Rimas V.; Rodon, Jordi; Becker, Kevin; Wong, Eric T.; Shih, Kent; Touat, Mehdi; Fassò, Marcella; Osborne, Stuart; Molinero, Luciana; O’Hear, Carol; Grossman, William; Baehring, Joachim
- Abstract
Purpose: Glioblastoma is the most common primary malignant brain tumor. No standard treatment exists for recurrent disease. Glioblastoma is associated with an immunosuppressive tumor microenvironment. Immune checkpoint inhibitors, including atezolizumab (anti-programmed death-ligand 1), have demonstrated clinical activity in various cancers. Here, we present the safety and efficacy of atezolizumab in patients with glioblastoma from the phase 1a PCD4989g clinical trial (NCT01375842).Methods: Eligible patients had confirmed recurrent glioblastoma and measurable disease per RANO criteria. Atezolizumab (1200 mg) was administered intravenously every 3 weeks until progression or unacceptable toxicity. Patients were monitored for safety; response was evaluated at least every 6 weeks. Baseline biomarkers were evaluated.Results: All 16 patients enrolled had received prior chemotherapy, and 50% prior bevacizumab. Ten patients (63%) experienced a treatment-related event. No treatment-related grade 4-5 events were reported. All deaths occurred due to progression or during follow-up. One patient experienced a partial response (5.3 months); 3 experienced disease stabilization. The median overall survival was 4.2 months (range 1.2 to 18.8+ months). Association between peripheral CD4+ T cells and efficacy was observed. Two patients with IDH1-mutant tumors and 1 with a POLE-mutant tumor experienced ≥ 16 months survival.Conclusions: Atezolizumab was safe and well tolerated in this group of patients with recurrent glioblastoma. Our preliminary findings suggest that biomarkers, including peripheral CD4+ T cells and hypermutated tumor status, may help guide selection of patients with recurrent glioblastoma who might receive most benefit from atezolizumab therapy, supporting further atezolizumab combination studies in glioblastoma.
- Subjects
GLIOMAS; DISEASE progression; CANCER chemotherapy; BIOLOGICAL tags; HUMAN research subjects
- Publication
Journal of Neuro-Oncology, 2018, Vol 140, Issue 2, p317
- ISSN
0167-594X
- Publication type
Article
- DOI
10.1007/s11060-018-2955-9