PD-1/ PD-l1 Inhibitors and Stereotactic Radiosurgery for Brain Metastases: a systematic review and meta-analysis.
Yara Alswaiti, Ghena Shahwan, Bakr Alhayek et al.
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In 30 seconds
This systematic review and random-effects meta-analysis assessed efficacy and toxicity when PD-1/PD-L1 inhibitors were combined with stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) for brain metastases. It included 34 studies comprising 2,587 patients. Pooled one-year overall survival was 65% (95% CI 60-69), and one-year local control was 87% (95% CI 79-92). Grade 3 radiation-induced brain necrosis occurred in 5% (95% CI 3-8); the authors considered the combined approach feasible but noted that prospective trials are needed to clarify incremental necrosis risk.
Key findings
- Pooled one-year overall survival was 65% (95% CI 60-69); estimates were 68% for NSCLC brain metastases and 61% for melanoma brain metastases.
- One-year local control was 87% (95% CI 79-92), while distant intracranial progression-free survival was 40.23% (95% CI 17.99-62.47).
- Grade 3 radiation-induced brain necrosis had a cumulative incidence of 5% (95% CI 3-8); no significant difference was found between melanoma and NSCLC subgroups.
- Grade ≥ 3 neurological events occurred in 7% (95% CI 4-13).
Why it matters
The pooled outcomes provide a clinical overview of intracranial control and serious toxicity reported with SRS or FSRT alongside PD-1/PD-L1 inhibitors. The findings suggest the combination can be delivered with a relatively low reported incidence of grade 3 brain necrosis, while highlighting that toxicity estimates and efficacy outcomes do not establish the added benefit or risk attributable to combining treatments.
What to keep in mind
The analysis pooled 34 studies using a single-arm model, so it cannot establish comparative benefit or isolate the incremental risk of brain necrosis. The authors state that prospective trials are needed.