The combined use of steroids and immune checkpoint inhibitors in brain metastasis patients: a systematic review and meta-analysis

Abstract

Background Immune checkpoint inhibitors (ICI) have been a breakthrough for selected cancer patients, including those with brain metastases (BMs). Likewise, steroids have been an integral component of symptomatic management of BM patients. However, clinical evidence on the interaction between ICI and steroids in BM patients is conflicting and has not adequately been summarized thus far. Hence, the aim of this study was to perform a systematic literature review and meta-analysis on the association between steroid use and overall survival (OS) in BM patients receiving ICI. Methods A systematic literature search was performed. Pooled effect estimates were calculated using random-effects models across included studies. Results After screening 1145 abstracts, fifteen observational studies were included. Fourteen studies reported sufficient data for meta-analysis, comprising 1102 BM patients of which 32.1% received steroids. In the steroid group, median OS ranged from 2.9-10.2 months. In the non-steroid group, median OS ranged from 4.9-25.1 months. Pooled results demonstrated significantly worse OS (HR 1.84, 95% CI 1.22-2.77) and systemic progression free survival (PFS; HR 2.00, 95% CI 1.37-2.91) in the steroid group. Stratified analysis showed a consistent effect across the melanoma subgroup; not in the lung cancer subgroup. No significant association was shown between steroid use and intracranial PFS (HR 1.31, 95% CI 0.42-4.07). Conclusions Administration of steroids was associated with significantly worse OS and PFS in BM patients receiving ICI. Further research on dose, timing, and duration of steroids is needed to elucidate the cause of this association and optimize outcomes in BM patients receiving ICI.

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“…Symptomatic BMs often have poor efficacy and outcome. Besides active BMs per se, the decline in the efficacy of immunotherapy is attributed to steroids, which are considered immune suppressors and routinely used to control intracranial symptoms and modify side effects of other therapies in patients with BMs ( 14 , 98 ). Moreover, harboring driver-gene mutation, indicating a favorable prognosis, is associated with low benefits from ICIs ( 99 ).…”

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