Abstract
Lung cancer is one of the most common cancers and the leading cause of cancer-related deaths worldwide. Most of these patients with non-small cell lung cancer (NSCLC) present with the advanced stage of the disease at the time of diagnosis, and thus decrease the 5-year survival rate to about 5%. Immune checkpoint inhibitors (ICIs) can act on the inhibitory pathway of cancer immune response, thereby restoring and maintaining anti-tumor immunity. There are already ICIs targeting different pathways, including the programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen 4 (CTLA-4) pathway. Since March 2015, the US Food and Drug Administration (FDA) approved nivolumab (anti-PD-1 antibody) as the second-line option for treatment of patients with advanced squamous NSCLC. Additionally, a series of inhibitors related to PD-1/PD-L1 immune-checkpoints have helped in the immunotherapy of NSCLC patients, and modified the original treatment model. However, controversies remain regarding the use of ICIs in a subgroup with targeted oncogene mutations is a problem that we need to solve. On the other hand, there are continuous efforts to find biomarkers that effectively predict the response of ICIs to screen suitable populations. In this review, we have reviewed the history of the continuous developments in cancer immunotherapy, summarized the mechanism of action of the immune-checkpoint pathways. Finally, based on the results of the first-line recent trials, we propose a potential first-line immunotherapeutic strategy for the treatment of the patients with NSCLC.
Highlights
The lung cancer is one of the most frequent malignant tumors, and ranks first in the incidence and mortality among all the cancer types globally (Bray et al, 2018)
Our analysis indicated the nivolumab monotherapy to be ineffective in extending the progression-free survival (PFS) and overall survival (OS) than that achieved with chemotherapy in the control arm (PFS: 4.2 months versus 5.9 months; OS: 14.4 months versus 13.2 months; overall response rate (ORR): 26.1 versus 33.5%, respectively)
The results suggested that the administration of nivolumab monotherapy effectively increased the ORR and conferred significantly better OS than treatment with second-line docetaxel
Summary
The lung cancer is one of the most frequent malignant tumors, and ranks first in the incidence and mortality among all the cancer types globally (Bray et al, 2018). Only a small percentage of the patients with NSCLC are diagnosed at an early stage, while the majority of them present with locally advanced or metastatic disease at diagnosis, which accounts for their low five-. Platinum-based chemotherapy and radiation therapy are the traditional treatment methods for such tumors (Hanna et al, 2017; Tabchi et al, 2017), the last decade has shown the emergence of the molecular targeted therapies, including the tyrosine kinase inhibitors (TKI) targeting the epidermal growth factor receptor (EGFR), and the immunecheckpoint inhibitors (ICIs) that have helped improve the outcome of the patients with NSCLC (Hirsch et al, 2017; Dong et al, 2018). Despite the clinical benefits of immunotherapy, only a small proportion of the patients with NSCLC respond to ICIs administered as monotherapy, and not all responders continue to respond indefinitely (Kim and Chen, 2016).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
