Cadonilimab Combined With Stereotactic Radiotherapy as Second-line Treatment for Brain Metastases

Lung cancer is the cancer with the highest morbidity and mortality in the world. The most common metastatic site of lung cancer is the brain. Radiotherapy is a classic treatment for brain metastases from lung cancer. Stereotactic radiosurgery (SRS) has image-guided technology, which can accurately find the location of the tumor with an accuracy of millimeters, and effectively reduce the radiation to the surrounding normal tissues. According to the relevant recommendations of the NCCN guidelines for Central nervous System Tumors (first edition 2022), SRS can be given priority to patients with newly diagnosed localized brain metastases or with stable systemic tumor control, which can better protect the cognitive function of patients. SRS should be considered initial therapy in patients with a limited number of brain metastases. Citation (S) : SRS should be considered especially in patients with good physical activity status (PS) and small total tumor volume. The brain was once considered to be an immune privilege organ, which can actively inhibit any immune response. The 2019 NCCN guidelines have recommended immune checkpoint inhibitors (ICIs) as the first-line treatment for some patients with lung cancer, and the application of ICIs in lung cancer with brain metastases is also being explored. Several phase III RCT studies have shown that immunotherapy prolongs the survival of patients with brain metastases. As a classic treatment for brain metastases from lung cancer, radiotherapy can promote the anti-tumor immune effect by inducing immunogenic cell death, exposing tumor-associated antigens, activating dendritic cells, changing the tumor microenvironment, and enhancing the expression of intercellular adhesion molecule-1 (ICAM-1), Fas and major histocompatibility complex Ⅰ (MHCⅠ) in tumor cells. High-dose fractionated radiotherapy also has immunogenicity, which may open the blood-brain barrier (BBB) and promote the entry of ICI into brain tissue. However, radiotherapy can up-regulate the expression of PD-L1 and inhibit tumor immunity, which can be improved by ICI. In conclusion, intracranial radiotherapy combined with ICIs has feasibility and theoretical basis for the treatment of malignant tumors. Cadonilimab is a bispecific antibody (BsAb) that can bind to both PD-1 and CTLA-4 with high affinity. It is a novel tumor immunotherapy drug with a quadrivalent structure and a short half-life, and has been shown to have less toxicity than the combination of anti-PD-1 and anti-CTLA-4 antibodies in monkey toxicity studies. These features make it possible that the use of Cadonilimab in cancer subjects may have better efficacy and safety. In conclusion, the combination of Cadonilimab with radiotherapy has potential advantages and is expected to have the potential to further improve antitumor efficacy. Therefore, the aim of this study is to evaluate the efficacy and safety of Cadonilimab combined with SRS in the treatment of brain metastases from NSCLC, and to provide evidence for future studies.