Clinical activity and safety of atezolizumab in patients with recurrent glioblastoma

• Published in: Journal of neuro-oncology 2018-11, Vol.140 (2), p.317-328
• Main 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
• Format: Article
• Language: English
• Subjects: Administration, Intravenous; Adult; Aged; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Apoptosis; Bevacizumab; Bevacizumab - therapeutic use; Biomarkers; Biomarkers, Tumor - metabolism; Brain cancer; Brain Neoplasms - drug therapy; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - mortality; Brain tumors; CD4 antigen; Chemotherapy; Clinical Study; DNA Polymerase II - genetics; Female; Follow-Up Studies; Glioblastoma; Glioblastoma - drug therapy; Glioblastoma - genetics; Glioblastoma - metabolism; Glioblastoma - mortality; Humans; Immune checkpoint inhibitors; Immunosuppression; Immunotherapy; Isocitrate Dehydrogenase - genetics; Lipids; Lymphocytes T; Male; Medicine; Medicine & Public Health; Middle Aged; Monoclonal antibodies; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - metabolism; Neoplasm Recurrence, Local - mortality; Neurology; Oncology; Patients; Poly-ADP-Ribose Binding Proteins - genetics; Safety; Targeted cancer therapy; Toxicity; Treatment Outcome
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1007/s11060-018-2955-9

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.