Xiuming Zhu,Hongming Pan,Lili Liu, Extremely Rapid Response to Pembrolizumab in a SMARCA4 Mutant PD-L1 Highly Expressive Advanced Lung Adenocarcinoma: A Case Report Surgical Case Reports 2021 2613-5965 http://dx.doi.org/10.31487/j.SCR.2021.11.07 https://www.sciencerepository.org/extremely-rapid-response_SCR-2021-11-107 Abstract: SMARCA4 mutant non-small cell lung cancer (SMARCA4m-NSCLC) has a poor prognosis owing to rapid growth. Effective treatments for SMARCA4m-NSCLC have not yet been established. Recently, many preclinical studies support the hypothesis that SMARCA4m-NSCLC may be vulnerable to immune checkpoint inhibitors. Here, we report a patient with programmed death-ligand1 (PD-L1) highly expressive SMARCA4m-NSCLC who showed an extremely rapid and long-term response to pembrolizumab. He was referred to our hospital for a mass of the right lung. Positron emission tomography-computed tomography showed right lung tumor, hilar, mediastinal and bone metastases. Pathological and immunohistochemical results showed it was a lung adenocarcinoma and revealed the tumor proportion score of PD-L1 was 80%. SMARCA4 and K-RAS genes were co-mutations. BRG1 protein expression was negative. Subsequently, pembrolizumab treatment as the first line of therapy was commenced for the patient. With only one dose, pembrolizumab significantly inhibited tumor growth and a partial response was obtained. To date, pembrolizumab treatment has been continued for about 29 months. Severe immune-related adverse events were not observed. Our case showed that an extremely rapid and long-term response can be achieved with pembrolizumab for PD-L1 highly expressive SMARCA4m-NSCLC. Immune checkpoint inhibitors treatment may be a promising strategy for PD-L1 positive SMARCA4m-NSCLC.Keywords: Non-small cell lung cancer, SMARCA4 mutant, PD-L1, immune checkpoint inhibitors