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Anti-PD-1/PD-L1 inhibitor therapy for melanoma brain metastases: a systematic review and meta-analysis
Mohammad Amin Habibi1, Mohammad Sina Mirjani2, Muhammad Hussain Ahmadvand3
1Department of Neurosurgery, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Abstract:
Melanoma brain metastases present a major challenge in cancer treatment and reduce overall survival despite advances in managing primary melanoma. Immune checkpoint inhibitors (ICIs) that target PD-1/PD-L1 pathways have shown promise in treating advanced melanoma, but their efficacy for melanoma brain metastases is debated. This systematic review and meta-analysis summarize evidence on anti-PD-1/PD-L1 inhibitors for melanoma brain metastases. This systematic review and meta-analysis followed PRISMA guidelines. PICO criteria targeted melanoma brain metastasis patients treated with PD-1/PD-L1 inhibitors, assessing overall survival, progression-free survival, and complications. Inclusion criteria were English studies on humans using PD-1/PD-L1 inhibitors for melanoma brain metastases with > 10 patients. A total of 22 trials involving 1523 melanoma brain metastase patients treated with anti-PD-1/PD-L1 inhibitors were thoroughly analyzed. Our findings show the 6-month OS rate of 0.75 [95%CI:0.67-0.84], the 6-months PFS rate of 0.42 [95%CI:0.31-0.52], the 1-year OS rate of 0.63 [95%CI:0.52-0.74], the 1-year PFS rate was 0.45 [95%CI:0.32-0.58], the 18-months OS rate of 0.52 [95%CI:0.37-0.67], the 2-year OS rate of 50% [95% CI: (34%-65%)], the 2 year PFS rate of 0.36 (95%CI:0.23-0.50), the 3-year OS rate of 0.42 (95%CI:0.17-0.67), the 4-year PFS rate of 0.35 [95%CI:0.08-0.61], the 4-year OS rate of 0.29 [95%CI:0.01-0.56], the 5-year OS rate of 0.29 (95%CI:0.09-0.50), and the 5-year PFS rate of 0.11 (95%CI:0.03-0.19). The combined disease stability rate was 0.13 [95%CI:0.05-0.20], the progressive disease rate was 0.49 [95%CI:0.37-0.62], the partial response rate was 0.14 [95%CI:0.07-0.20], the object response rate was 0.35 [95%CI:0.24-0.46], and the complete response rate was 0.22 [95%CI:0.12-0.32]. In conclusion, our meta-analysis provides compelling evidence supporting the efficacy of PD-1/PD-L1 inhibitors in patients with melanoma brain tumors, as evidenced by favorable survival outcomes and disease control rates.
Insights
Immune checkpoint inhibitors targeting PD-1/PD-L1 pathways show efficacy in melanoma brain metastases. This meta-analysis of 22 trials confirms their benefit for patient survival and disease control.
Area of Science:
- Oncology
- Immunotherapy
- Melanoma Research
Background:
- Melanoma brain metastases significantly reduce survival despite advances in primary melanoma treatment.
- The efficacy of immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 pathways for melanoma brain metastases remains a subject of debate.
Purpose of the Study:
- To systematically review and meta-analyze evidence on the efficacy of anti-PD-1/PD-L1 inhibitors in patients with melanoma brain metastases.
- To assess overall survival (OS), progression-free survival (PFS), and response rates in this patient population.
Main Methods:
- Systematic review and meta-analysis adhering to PRISMA guidelines.
- Inclusion of 22 English-language studies involving 1523 patients with melanoma brain metastases treated with PD-1/PD-L1 inhibitors.
- Analysis focused on survival outcomes (OS, PFS) and response rates (complete response, partial response, stable disease, progressive disease).
Main Results:
- Significant survival rates observed: 6-month OS 0.75, 1-year OS 0.63, 2-year OS 0.50, and 5-year OS 0.29.
- Progression-free survival rates: 6-month PFS 0.42, 1-year PFS 0.45, 2-year PFS 0.36, and 5-year PFS 0.11.
- Objective response rate (ORR) was 0.35, with a complete response rate of 0.22 and a disease stability rate of 0.13.
Conclusions:
- This meta-analysis provides robust evidence supporting the efficacy of PD-1/PD-L1 inhibitors for treating melanoma brain metastases.
- Favorable survival outcomes and disease control rates indicate significant clinical benefit of these immunotherapies in this challenging condition.
