Lead Investigator: Xiaoling Shang, Shandong University
Title of Proposal Research: Survival analysis of advanced lung adenocarcinoma harboring epidermal growth factor receptor gene mutation receiving the combination treatment of atezolizumab, Bevacizumab,carboplatin and Paclitaxel.
Vivli Data Request: 7395
Funding Source: None
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Lung cancer is the leading cause of cancer mortality worldwide. Non-small cell lung cancer accounts for more than 80% of primary lung tumors. Lung adenocarcinoma is a pathological type of non-small cell lung cancer, accounting for about 40% of primary lung tumors. It is more likely to occur in women and non-smokers. The epidermal growth factor receptor mutation is the most common gene mutation in patients with lung adenocarcinoma, and the mutation incidence is as high as 50% in Asians with lung adenocarcinoma. The epidermal growth factor receptor tyrosine kinase inhibitors are the preferred treatment for these patients, and the effective rate is more than 60%-70%. And the median progression free survival, which is defined as the time between the beginning of treatment and the observation of disease progression or death from any cause, for patients using the first/second generation tyrosine kinase inhibitors is 9-13 months, and the median progression free survival of the third generation tyrosine kinase inhibitors is 18.9 months. However, epidermal growth factor receptor tyrosine kinase inhibitors resistance is inevitable in the later stage, and there is no effective treatment scheme for drug-resistant patients, which is an important clinical problem to be solved urgently.
Patients with epidermal growth factor receptor mutations reveals poor response to immunotherapy. Immunotherapy is a treatment method to artificially enhance and inhibit the immune function of the body in order to achieve the purpose of treating diseases. The purpose of tumor immunotherapy is to activate the human immune system and kill cancer cells and tumor tissues by relying on autoimmune function. Immunotherapy has a variety of classification methods, for example, targeting programmed death-1 or programmed death ligand-1. Programmed death-1 (PD-1) is a regulatory protein of T lymphocytes, but it inhibits the immune killing effect of lymphocytes and reduces the killing effect of T lymphocytes on tumors, resulting in the occurrence of tumors. Programmed death ligand-1 (PD-L1) is a ligand protein produced by tumor cells, which can be combined with PD-1 of T lymphocytes. The immune recognition function of T lymphocytes is inhibited, so that T lymphocytes will not kill tumor cells with PD-L1 and the tumor can grow smoothly. Based on the above principles, the drugs of targeting PD-1/PD-L1 can specifically combine with PD-1/PD-L1, so as to relieve the immunosuppressive regulation of T lymphocytes, so that T lymphocytes can kill tumor cells.
The subgroup analysis of IMPower 150 revealed a preliminary effect on patients with epidermal growth factor receptor mutations who received programmed death ligand-1 and anti-angiogenesis plus chemotherapy with better prognosis. Anti-angiogenesis is a method that can inhibit the growth of blood vessels and without a stable blood supply, the tumor stops growing and many cancer cells in the tumor eventually die. This clinical dataset brings hope to patients with epidermal growth factor receptor mutations who are not responsive to immune checkpoint inhibitors monotherapy, suggesting a dramatically improvement of science and health.
A Phase III, Open-Label, Randomized Study of Atezolizumab (MPDL3280A, Anti-PD-L1 Antibody) in Combination With Carboplatin+Paclitaxel With or Without Bevacizumab Compared With Carboplatin + Paclitaxel + Bevacizumab in Chemotherapy-Naïve Patients With Stage IV Non-Squamous Non-Small Cell Lung Cancer
Data Contributor: Roche
Study ID: NCT02366143
Sponsor ID: GO29436