Introduction
a) Background: Lung cancer is one of the most frequently diagnosed cancers and the leading cause of cancer-related deaths worldwide [1] .Lung cancer, also known as primary bronchial lung cancer, is divided into small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC), of which NSCLC accounts for about 85% of all lung cancer types. Adenocarcinoma, a type of NSCLC, is the least associated with smoking and accounts for 40% of primary lung tumors[2]. It is often located in the peripheral part of the lung, which also involves the pleura and forms an associated scarring circle and pleural effusion, and has a poor prognosis. Malignant pleural effusion (MPE) is a common complication of advanced lung adenocarcinoma (LAC) associated with a poor life expectancy[3]. The expression of vascular endothelial growth factor, a factor that has recently been shown to play an important role in the formation of malignant pleural effusions, has increased significantly, leading to the emergence of angiogenesis inhibitors as a key approach to control tumour progression[4].
b) Rationale and knowledge gap: The efficacy of chemotherapy for advanced NSCLC has reached a plateau, and molecular targeted therapy has gradually become a hot topic for scholars. The formation of new blood vessels is one of the main mechanisms of tumor growth and resistance, and it also provides a pathway for tumor cell migration and distant metastasis. The recombinant human vascular endothelial inhibitor, Endostatin, is a novel biologic agent for the treatment of tumors. In addition to regulating VEGF expression, it participates in the regulation of multiple signal transduction pathways, thereby inhibiting tumor angiogenesis[5]. Bevacizumab is a humanized monoclonal antibody that selectively binds to vascular endothelial growth factor (VEGF), inhibiting the formation of tumor neovascularization and playing an anti-tumor role. Unlike conventional cancer treatments, immune checkpoint inhibitors do not attack cancer cells directly, but rather mobilize the immune system to re-identify cancer cells that have escaped surveillance, allowing the immune system to function again. Camrelizumab is a novel human immunoglobulin G4 (IgG4)-based monoclonal antibody (mAb) that blocks pathways associated with PD-1 and PD-L1, deregulates t-cell immunosuppression, and enhances t-cell killing of tumor cells.
Previous studies have confirmed that serum levels of tumor markers such as neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), cytokeratin 19 fragments (CYFRA21-1), carbohydrate antigen 125 (CA125)and carbohydrate antigen 153 (CA153) are significantly higher in lung cancer patients than in patients with benign lung lesions and healthy individuals, and the levels are significantly higher in patients with postoperative recurrence than in patients without recurrence[6, 7]. It indicates that serum tumor markers have an important impact on the prognosis of lung cancer patients, while the treatment effect and 5-year survival rate of lung cancer are related to early diagnosis and early treatment[8]. This is closely related to early diagnosis and early treatment. Imaging examination and histocytological examination are the main means to diagnose lung cancer, but both of them have disadvantages such as low sensitivity and specificity and invasiveness. Tumor markers have a higher sensitivity for tumor diagnosis, in addition, serum specimens are more easily available and less invasive to the body.
c) Objective: Recent treatment guidelines have recommended the combination of immune checkpoint inhibitors and anti-angiogenic drugs for the treatment of stage IV lung adenocarcinoma[9], and clinical trials have evaluated the efficacy of this regimen camrelizumab combined with bevacizumab, but there are no specific clinical indicators. Although current monotherapy with immune checkpoint inhibitors (ICIs) has a manageable safety profile, their efficacy is greatly limited by low response rates. Therefore, scientists have sought various combination therapies in an effort to improve response rates to ICIs. Combination regimens have primarily shown better in vivo clinical activity compared to monotherapy; however, the management of adverse effects is also more problematic. There is still a lack of long-term follow-up evidence to confirm the durable response and survival benefits from combination therapies of ICLs combined with anti-angiogenesis.
Based on this background, this case adjusted camrelizumab in combination with recombinant human vascular endothelial inhibitor to camrelizumab in combination with bevacizumab for stage IV lung adenocarcinoma and continued long term follow up, which is reported in detail below.