Immunotherapy for Non-Small-Cell Lung Cancer: The Past 10 Years

Abstract

In the past decade, the approach to patients with metastatic non-small-cell lung cancer has relied on chemotherapy and on targeted agents for molecularly selected subgroups of patients. Recent work has introduced immunotherapy as another area of progress, and likely as a new treatment paradigm in the near future. While the large Phase III studies with cancer vaccination with the current technologies remain at present disappointing, the immunomodulation strategies with immune checkpoint inhibitors have delivered remarkable results in expanded Phase I studies and are now intensively studied in large Phase III studies. This review summarizes the past decade of immunotherapy for non-small-cell lung cancer, gives an updated overview of trials in this field, and the context of future development in this exciting field.

Safety and Efficacy of Durvalumab (MEDI4736), an Anti–Programmed Cell Death Ligand-1 Immune Checkpoint Inhibitor, in Patients With Advanced Urothelial Bladder Cancer

“…20,[28][29][30] However, a lack of standardized assays and metrics for defining PD-L1 positivity has resulted in inconsistencies in the literature and confusion regarding how best to select patients for treatment. Recently, a variety of assays to assess PD-L1 expression and thresholds to define PD-L1-positive status have been used, and expression on TC, IC, or both has been considered.…”

Beyond checkpoint inhibition – Immunotherapeutical strategies in combination with radiation

“…Whereas immune checkpoint inhibition is the most advanced immunotherapeutic strategy already established in several different indications [2] , [115] , [116] , [117] and is FDA approved for advanced melanoma, non-small cell lung cancer and other cancer entities such as urothelial bladder cancer [118] , other immunotherapeutic approaches also merit further attention. Immune checkpoint inhibition might be more effective in combination with other immunotherapy strategies or anti-cancer treatment as indicated by the findings of Badoual et al [119] .…”

Immune Checkpoint Inhibitors as First-Line and Salvage Therapy for Advanced Non-Small-Cell Lung Cancer

“…The advantages of this approach in NSCLC were realized after the discovery of activating EGFR mutations [76], which predict sensitivity to EGFR-TKIs [77]. An effective biomarker for immunotherapy predicts for a high ORR, increases the benefit/risk ratio and may reduce treatment cost [11]. PD-L1 is the most widely studied biomarker in this setting.…”

“…The results of immunotherapy in NSCLC have been, until recently, disappointing as a range of agents showed no beneficial results (reviewed in [9,11]). It was the recognition of the pivotal role of CTLA-4, as a negative regulator of immunity [12,13] and the effect of its functional blockade [14] in the mid 1990s that led to an increased understanding of how to develop more effective immunotherapy agents.…”