Effectiveness of PD-1/PD-L1 inhibitors in the treatment of lung cancer: Brightness and challenge
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fectiveness of PD-1/PD-L1 inhibitors in the treatment of lung cancer: Brightness and challenge *
Ying Yang, Yongfeng Yu & Shun Lu
Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 20030, China Received November 30, 2019; accepted January 4, 2020; published online April 15, 2020
Immune checkpoint inhibitors (ICIs), especially inhibitors of the PD-1/PD-L1 axis, have significantly affected the outcomes of patients with lung cancer. Nivolumab and pembrolizumab have been approved as PD-1 blocking antibodies, whereas atezolizumab, avelumab, and durvalumab are approved as PD-L1 blocking antibodies by the United States Food and Drug Administration. However, which patient may benefit the most and how to identify patients at risk of primary or acquired resistance has not been completely defined. Meanwhile, close attention has been paid to the ongoing international and domestic clinical trials in Chinese patients with lung cancer. This review aimed to provide deep insight into the effectiveness of PD-1/PD-L1 inhibitors in patients with lung cancer, including the current settings for varied disease status, the predictive biomarkers, the resistance to ICIs, and the ongoing clinical trials in Chinese patients. immunotherapy, PD-1/PD-L1 inhibitors, lung cancer Citation:
Yang, Y., Yu, Y., and Lu, S. (2020). Effectiveness of PD-1/PD-L1 inhibitors in the treatment of lung cancer: Brightness and challenge. Sci China Life Sci 63, https://doi.org/10.1007/s11427-019-1622-5
Introduction Lung cancer is the leading cause of death worldwide, accounting for an estimated 2.09 million new cases in 2018, according to the World Health Association, and it is also the leading cause of cancer-related mortality in China (Chen et al., 2015). Lung cancer is mainly categorized as small cell lung cancer (SCLC, 10%–15%) and non-small cell lung cancer (NSCLC, 80%–85%). More than 50% of patients with NSCLC present with metastases at the initial diagnosis. Limited treatment options are available for both advanced NSCLC and SCLC. Platinum-doublet chemotherapy served as a first-line treatment for patients with advanced NSCLC and wild-type. The emergence of tyrosine kinase inhibitor (TKIs) has dramatically changed the prognosis of patients harboring driver genes, including those with sensitive EGFR *Corresponding author (email: [email protected])
mutations, ALK fusion, or ROS1 rearrangements. TKIs targeting these genes have been approved as first-line therapy for patients with NSCLC having the above molecular subtypes. Immunotherapy is one of the most significant breakthroughs in lung cancer therapy during the last decade. In the CA209-003 study of nivolumab administered in patients with previously treated advanced NSCLC, the 5 year overall survival (OS) rate was 16% at 5 years of follow-up (Gettinger et al., 2018). In the Keynote-001 study, pembrolizumab also demonstrated significant antitumor activity, and the 5 year OS rates were 23.2% for treatment-naive patients and 15.5% for previously treated patients (Ga
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