Targeted therapies (TT), combo-immunotherapy (CMI) and mono-immunotherapy (MI) in combination (CRI) or not with radiotherapy are commonly used in patients with melanoma brain metastases (MBMs), but studies that directly compare these strategies are lacking. This meta-analysis aimed to better elucidate their activity and efficacy.
A systematic search of Medline, Embase and conferences proceedings up to January 2019 was carried out to identify trials investigating combo TT, mono TT, MI, CMI, CRI in MBMs. The outcomes considered were progression free survival (PFS), overall survival (OS) and objective response rate (ORR) evaluated at both intra and extra-cranial sites. Random effects models were used to compare the different therapeutic strategies.
We included 15 trials, which provided 1132 patients for analyses. CMI showed a statistically significant better OS than MI (p = 0.03, p = 0.05, p = 0.03 at 6, 18 and 24 months respectively) and combo TT (p = 0.04, p = 0.03, at 18 and 24 months respectively). CMI showed a statistically significant better PFS compared to combo TT (p < 0.001 at 12 and 18 months), MI (p = 0.02, p < 0.02 and p = 0.05 at 6, 12 and 18 months respectively) and mono TT (p < 0.001 at 6, 12 and 18 months respectively). The intracranial ORR was higher with CMI compared to mono TT (p < 0.001) and MI (p < 0.001), while there was no difference between CMI and combo TT.
This meta-analysis suggests that CMI increases long term PFS and OS compared to MI and combo TT. Combo TT and CMI are associated with a similar intracranial response rate. The role systemic therapy in combination with radiotherapy remains to be better elucidated.
Clinical trial identification
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All authors have declared no conflicts of interest.