Abstract
Background/Objectives: Non-small-cell lung cancer (NSCLC) frequently metastasizes to the brain, significantly impacting patient prognosis and quality of life. Anlotinib, a novel tyrosine kinase inhibitor, has shown promise in treating NSCLC with brain metastasis. So, we aimed to evaluate the clinical efficacy of anlotinib and various types of radiotherapy combinations used to treat NSCLC patients with brain metastasis regarding overall survival and the treatment of internal and external lesions. Methods: A comprehensive literature search was conducted in the databases PubMed, Scopus, WoS, MedLine, and Cochrane Library up to April 2024. Studies assessing the efficacy of anlotinib combined with whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), or other radiotherapy modalities in NSCLC patients with brain metastasis were included. The primary outcomes were (a) the efficacy of anlotinib and radiotherapy on the intracranial lesions and OS and (b) the effectiveness of combined anlotinib and radiotherapy versus radiotherapy alone in NSCLC patients with brain metastasis. The secondary outcome was the efficacy of anlotinib and radiotherapy on extracranial progression. We used a combination of keywords and MeSH terms including 'non-small cell lung cancer' OR 'NSCLC', 'brain metastases', 'anlotinib', 'radiotherapy', 'radiation therapy', and 'combined treatment', among others. Boolean operators (AND, OR) were applied as appropriate to optimize the search strategy across databases. Results: Nine studies met the inclusion criteria, comprising 210 patients in the combination group and 228 patients in the radiotherapy alone group. The combination of anlotinib with radiotherapy showed a significant improvement in iPFS compared to radiotherapy alone, with a pooled risk ratio (RR) for iORR of 1.18 (95% CI: 1.00-1.39) and a pooled SMD for OS of 0.03 (95% CI: -0.29, 0.36). Radiotherapy combined with anlotinib also demonstrated enhanced intracranial and extracranial control rates. Conclusions: Anlotinib combined with radiotherapy, especially WBRT, offers a promising treatment strategy for NSCLC patients with brain metastasis, improving intracranial control. Further large-scale randomized controlled trials are needed to confirm these findings and optimize treatment protocols.