The Current Status of Immune Checkpoint Inhibitors in Neuro-Oncology: A Systematic Review.

Cyrillo G Brahm,René H.J Otten,Roelien H Enting,Martijn W Heymans,Myra E Van Linde,Annemiek M.E Walenkamp,Henk M.W Verheul,Maaike Schuur

doi:10.3390/cancers12030586

Abstract

The introduction of immune checkpoint inhibitors (ICI), as a novel treatment modality, has transformed the field of oncology with unprecedented successes. However, the efficacy of ICI for patients with glioblastoma or brain metastases (BMs) from any tumor type is under debate. Therefore, we systematically reviewed current literature on the use of ICI in patients with glioblastoma and BMs. Prospective and retrospective studies evaluating the efficacy and survival outcomes of ICI in patients with glioblastoma or BMs, and published between 2006 and November 2019, were considered. A total of 88 studies were identified (n = 8 in glioblastoma and n = 80 in BMs). In glioblastoma, median progression-free (PFS) and overall survival (OS) of all studies were 2.1 and 7.3 months, respectively. In patients with BMs, intracranial responses have been reported in studies with melanoma and non-small-cell lung cancer (NSCLC). The median intracranial and total PFS in these studies were 2.7 and 3.0 months, respectively. The median OS in all studies for patients with brain BMs was 8.0 months. To date, ICI demonstrate limited efficacy in patients with glioblastoma or BMs. Future research should focus on increasing the local and systemic immunological responses in these patients.

Highlights

Treating patients with primary brain tumors and brain metastases can be challenging
For the future of immunotherapy in glioblastoma, research should focus on a multi-modal approach to activate local and systemic tumor-specific immune responses in glioblastoma
In patients with melanoma and non-small-cell lung cancer (NSCLC) brain metastases, intracranial objective responses are seen with checkpoint inhibitors

Summary

Introduction

Treating patients with primary brain tumors and brain metastases can be challenging. This is primarily due to the poor prognosis of these patients despite maximal treatment and the presence of the blood–brain barrier, posing an obstacle to overcome for most systemic treatments [1]. Since the addition of TMZ to postoperative treatment, two-year and five-year survival have improved to 27% and 10%, respectively [3]. The addition of tumor-treating fields, an anti-mitotic treatment modality, to TMZ maintenance therapy demonstrated a statistically significant improvement in progression-free and overall survival, compared to TMZ maintenance therapy alone (6.7 months vs 4.0 months and 20.9 months vs 16.0 months, respectively) [4]. At the time of recurrence, options are limited due to the distinct limitations in the use of surgery and re-irradiation, and the poor treatment response to chemotherapy and targeted therapy [5,6,7]

Methods

Results

Discussion

Conclusion