Abstract
Simple SummaryThe following paper was developed as a reference for healthcare workers who are looking for information on advanced non-small cell lung cancers that lack driver mutations and their treatment with immunotherapy. The aim of the present study is to provide a reliable data source based on a review of the most current papers on the PD-1/PD-L1 and CTLA-4 inhibitors, as well as their use in medical practice.From a complete literature review, we were able to present in this paper what is most current in the treatment with immunotherapy for advanced non-small cell lung cancer (NSCLC). Especially the use of immunotherapy, particularly inhibitors of PD-1 (programmed cell death protein 1), PDL-1 (programmed cell death protein ligand 1), and CTLA-4 (cytotoxic T-lymphocyte antigen 4). Since 2015, these drugs have transformed the treatment of advanced NSCLC lacking driver mutations, evolving from second-line therapy to first-line, with excellent results. The arrival of new checkpoint inhibitors such as cemiplimab and the use of checkpoint inhibitors earlier in the therapy of advanced and metastatic cancers has been making the future prospects for treating NSCLC lacking driver mutations more favorable and optimistic. In addition, for those patients who have low PDL-1 positivity tumors, the combination of cytotoxic chemotherapy, VEGF inhibitor, and immunotherapy have shown an important improvement in global survival and progression free survival regardless the PDL-1 status. We also explored the effectiveness of adding radiotherapy to immunotherapy and the most current results about this combination. One concern that cannot be overlooked is the safety profile of immune checkpoint inhibitors (ICI) and the most common toxicities are described throughout this paper as well as tumor resistance to ICI.
Highlights
Lung cancers are histologically divided into Small Cell Lung Cancer (SCLC), which is found in about 15% of patients, and Non-Small Cell Lung Cancer (NSCLC), which is the most common type, found in the remaining 85% of patients [1]
The study demonstrated that in treatment-naive metastatic NSCLC cancer patients, there was a significant gain in overall survival with the association of pembrolizumab with chemotherapy, and this result was seen in all categories of PDL-1 expression positivity
For patients with PDL-1 status ≤ 5%, the use of immunotherapy combined with chemotherapy and/or VEGF inhibitors appears as an excellent treatment option, bringing beneficial results both for overall survival and for progression-free survival in addition to good tolerance and a good safety profile for patients
Summary
Ten distinct biological characteristics, called Hallmarks of Cancer, acquired in the course of tumor development and can significantly determine the process of carcinogenesis These Hallmarks are: capacity for proliferative signaling, inhibition of growth suppressor signals, evasion of immune destruction, mechanisms of resistance to apoptosis, promotion of inflammation in the tumor microenvironment, replicative immortality, genomic instability, induction of angiogenesis, ability to metastasize, and dysregulation of cellular metabolism. We have the option of using immunotherapy for NSCLC that lack the most common driver mutations and for those that become resistant to targeted therapy of driver mutations [16,17] This therapy plays a key role in the treatment of patients with non-small cell lung cancer of squamous and non-squamous etiology who do not have driver gene mutations [18]. In addition to the PDL pathway, cancer cells can inhibit the activation of lymphocytes and lead them to apoptosis by expressing molecules that bind to CTLA-4 (cytotoxic T-lymphocyte antigen 4), an inhibitory receptor present on the surface of lymphocytes [24,25]
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