Clinical activity and safety of atezolizumab in patients with recurrent glioblastoma
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).
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.
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.
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.
KeywordsAtezolizumab Glioblastoma (GBM) Programmed death-ligand 1 (PD-L1) Tumor mutational burden (TMB)
We thank the patients, their families, and the clinical study site investigators and staff. We also thank Daniel Chen, Gregg Fine, and Cathi Ahearn, of Genentech, Inc., and Helene Cauwel, of Cytel, for their contributions to the study. The authors also thank Dr Roger Stupp for critical review of the manuscript. Medical writing assistance for this manuscript was provided by Minna Balbas, PhD, of Health Interactions, Inc, and funded by F. Hoffmann-La Roche, Ltd. Dr. Lukas is supported by P50CA221747 SPORE for Translational Approaches to Brain Cancer.
This work was supported by F. Hoffmann-La Roche, Ltd.
Compliance with ethical standards
Conflict of interest
RVL has received support from Roche-Genentech for meeting travel to present study results, honoraria for advisory boards for AstraZeneca, Abbvie, and Ziopharm and honoraria for medical editing for EBSCO publishing, Medlink Neurology, and American Physician Institute. JR has received honoraria for advisory boards from Novartis, Lilly, Orion, Servier, and Peptomyc, and has received research funding from Bayer and Novartis. JB has received honoraria for advisory boards from BMS. MF is an employee of, and has stock options with Roche-Genentech, and has stock options and a patent with Aduro BioTech. CO and LM are employees of, and have stock options with Roche-Genentech. SO is an employee of Roche-Genentech. WG, MT, ETW, KS and KB have no conflicts to disclose.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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