The impact of targeted therapies and immunotherapy in melanoma brain metastases: A systematic review and meta‐analysis

Abstract

Targeted therapies (TT), combination immunotherapy (CMI), and monoimmunotherapy (MI) in combination with radiotherapy (CRI) or not are commonly used in patients with melanoma brain metastases, but studies that directly compare these strategies are lacking. The current meta-analysis aimed to better elucidate their activity and efficacy. A systematic search of MEDLINE, Embase, and conference proceedings up to January 2019 was performed to identify trials investigating combination TT, monotargeted TT (mono TT), MI, CMI, and CRI in melanoma brain metastases. The outcomes considered were progression-free survival (PFS), overall survival (OS), and the objective response rate (ORR) as evaluated at both intracranial and extracranial sites. Random effects models were used to compare the different therapeutic strategies. A total of 15 trials were included that provided 1132 patients for analyses. CMI demonstrated a statistically significant better OS compared with MI (P=.03, P=.05, and P=.03, respectively, at 6months, 18months, and 24months) and combination TT (P=.04 and P=.03, respectively, at 18months and 24months). CMI demonstrated a statistically significant better PFS compared with combination TT (P<.001 at 12months and 18months), MI (P=.02, P<.02, and P=.05, respectively, at 6months, 12months, and 18months), and mono TT (P<.001 at 6months, 12months, and 18months). The intracranial objective response rate was higher with CMI compared with mono TT (P<.001) and MI (P<.001), whereas there was no difference between CMI and combination TT. The results of the current meta-analysis suggested that CMI increases long-term PFS and OS compared with MI and combination TT. Combination TT and CMI are associated with a similar intracranial response rate. The role of systemic therapy in combination with radiotherapy remains to be better elucidated.