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J Neurooncol. 2018 Nov;140(2):317-328. doi: 10.1007/s11060-018-2955-9. Epub 2018 Aug 2.

Clinical activity and safety of atezolizumab in patients with recurrent glioblastoma.

Author information

1
Department of Neurology, Northwestern University, 710 N. Lake Shore Drive, Abbott Hall 1114, Chicago, IL, 60611, USA. rimas.lukas@nm.org.
2
Department of Neurology, University of Chicago, Chicago, USA. rimas.lukas@nm.org.
3
Vall D'Hebron Institute of Oncology, Barcelona, Spain.
4
Yale School of Medicine, New Haven, USA.
5
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA.
6
Sarah Cannon Research Institute, Nashville, USA.
7
Gustave Roussy, Villejuif, France.
8
Genentech, Inc., South San Francisco, USA.
9
F. Hoffmann-La Roche Ltd., Basel, Switzerland.

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.

KEYWORDS:

Atezolizumab; Glioblastoma (GBM); Programmed death-ligand 1 (PD-L1); Tumor mutational burden (TMB)

PMID:
30073642
DOI:
10.1007/s11060-018-2955-9
[Indexed for MEDLINE]

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