Weathers et al. reported that the concurrent use of atezolizumab in combination with radiation and TMZ was safe, and demonstrated efficacy consistent with published trials for newly diagnosed GBM. Patients harboring an EGFR mutation had a relatively worse mOS compared to those with a PTEN mutation. Gene set enrichment analysis identified multiple immune-related gene sets enriched in patients with longer OS, suggesting that a subset of GBM tumors exhibited higher immune infiltration. These immune-infiltrated tumors showed enrichment for the mesenchymal GBM subtype, distinct fecal microbiome profiles, and specific immune cell populations.
Contributed by Shishir Pant
ABSTRACT: This phase I/II trial aims to evaluate the efficacy of concurrent atezolizumab with radiation therapy and temozolomide (TMZ) followed by adjuvant atezolizumab and TMZ in newly diagnosed glioblastoma (GBM) patients and to identify pre-treatment correlates with outcome (N = 60). Trial number: NCT03174197. The primary outcome was overall survival (OS) whereas secondary outcomes were retrospective global-omics analyses to identify pre-treatment immune and genetic tumor features that correlated with survival. Concurrent use of atezolizumab with radiation and TMZ demonstrated OS in line with published trials for newly diagnosed GBM. Tumor genomic (WES and/or targeted NGS panel), transcriptomic (RNAseq) and tissue microenvironment imaging, as well as fecal metagenomic sequencing were conducted. Gene set enrichment analysis of tumors identified multiple immune-based transcriptomic programs to distinguish patients with longer versus shorter survival (p ≤ 0.01). GBM immune enrichment was highly associated with the pre-treatment tumor mesenchymal subtype and patient gastrointestinal bacterial taxa profile.
Author Info: (1) Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, 1515 Holcombe Blvd, Houston, TX, 77030, USA. sweathers@mdanderson.org. (2) Genomic Med
Author Info: (1) Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, 1515 Holcombe Blvd, Houston, TX, 77030, USA. sweathers@mdanderson.org. (2) Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, 1515 Holcombe Blvd, Houston, TX, 77030, USA. (3) Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, 1515 Holcombe Blvd, Houston, TX, 77030, USA. (4) Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, 1515 Holcombe Blvd, Houston, TX, 77030, USA. (5) Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, 1515 Holcombe Blvd, Houston, TX, 77030, USA. (6) Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, 1515 Holcombe Blvd, Houston, TX, 77030, USA. (7) Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, 1515 Holcombe Blvd, Houston, TX, 77030, USA. (8) Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, 1515 Holcombe Blvd, Houston, TX, 77030, USA. (9) Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, 1515 Holcombe Blvd, Houston, TX, 77030, USA. (10) Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, 1515 Holcombe Blvd, Houston, TX, 77030, USA. (11) Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, 1515 Holcombe Blvd, Houston, TX, 77030, USA. (12) Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, 1515 Holcombe Blvd, Houston, TX, 77030, USA. (13) Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, 1515 Holcombe Blvd, Houston, TX, 77030, USA. (14) Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, 1515 Holcombe Blvd, Houston, TX, 77030, USA. (15) Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, 1515 Holcombe Blvd, Houston, TX, 77030, USA. (16) Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, 1515 Holcombe Blvd, Houston, TX, 77030, USA. (17) Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, 1515 Holcombe Blvd, Houston, TX, 77030, USA. (18) Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, 1515 Holcombe Blvd, Houston, TX, 77030, USA. (19) Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, 1515 Holcombe Blvd, Houston, TX, 77030, USA. (20) Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, 1515 Holcombe Blvd, Houston, TX, 77030, USA. (21) Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, 1515 Holcombe Blvd, Houston, TX, 77030, USA. (22) Genentech, Inc 1 DNA Way, San Francisco, CA, 94080, USA. (23) Genentech, Inc 1 DNA Way, San Francisco, CA, 94080, USA. (24) Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, 1515 Holcombe Blvd, Houston, TX, 77030, USA. (25) Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, 1515 Holcombe Blvd, Houston, TX, 77030, USA. (26) Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, 1515 Holcombe Blvd, Houston, TX, 77030, USA. john.degroot@ucsf.edu.
