2524 - The Impact of Sequencing Checkpoint Inhibitors and Radiotherapy on Clinical Outcomes of Patients with Melanoma Brain Metastases: Meta-Analysis of Comparative Studies

P. A. Haddad¹, and D. Kantamani²; ¹LSUHSC-S/Overton Brooks VAMC, Shreveport, LA, ²LSUHSC-S/Feist-Weiller Cancer Center, Shreveport, LA

Purpose/Objective(s): The rates of brain metastases in melanoma can approach a high of 50%, which portends an abysmal prognosis. Immunotherapy and radiotherapy have been shown to improve overall survival in patients with melanoma with brain metastases. However, the optimal sequence of immunotherapy and radiotherapy remains unclear. We conducted the following meta-analysis to evaluate the best sequence to improve progression-free and overall survival. Materials/

Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language, diagnosis of melanoma brain metastases, comparative studies of immune checkpoint inhibitors given before or after radiotherapy, and those that reported overall (OS) and progression-free (PFS) survival. Studies that reported mixed data that included concurrent immune checkpoint inhibitors with radiotherapy were excluded. A meta-analysis using the fixed effects and random effects models was conducted.
Results: Six retrospective comparative studies with a total of 213 patients were included. The median age was 62 years, and the median follow-up was 22 months. Initiating immunotherapy before radiotherapy was associated with worse PFS compared to radiotherapy followed by immunotherapy (HR=1.77, 95%CI 1.21-2.60, p=0.003; I²=13.5%). Furthermore, starting with immune checkpoint inhibitors followed by radiotherapy was associated with worse OS compared to radiotherapy followed by immunotherapy, but with borderline significance (HR=1.39, 95%CI 0.97-1.99, p=0.07; I²=0%).
Conclusion: This is the first and largest meta-analysis to date to show that in patients with melanoma brain metastases, the optimal sequence that impacts patients’ survival outcomes is to start with radiation therapy followed by immune checkpoint inhibitors.