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Immune checkpoint inhibitors: the new frontier in non-small-cell lung cancer treatment.

ABSTRACT: Lung cancer is the major cause for cancer-related death in the US. Although advances in chemotherapy and targeted therapy have improved the outcome of metastatic non-small-cell lung cancer, its prognosis remains dismal. A deeper understanding of the complex interaction between the immune system and tumor microenvironment has identified immune checkpoint inhibitors as new avenue of immunotherapy. Rather than acting directly on the tumor, these therapies work by removing the inhibition exerted by tumor cell or other immune cells on the immune system, promoting antitumoral immune response. To date, two programmed death-1 inhibitors, namely nivolumab and pembrolizumab, have received the US Food and Drug Administration approval for the treatment of advanced non-small-cell lung cancer that failed platinum-based chemotherapy. This manuscript provides a brief overview of the pathophysiology of cancer immune evasion, summarizes pertinent data on completed and ongoing clinical trials involving checkpoint inhibitors, discusses the different strategies to optimize their function, and outlines various challenges that are faced in this promising yet evolving field.

SUBMITTER: El-Osta H

PROVIDER: S-EPMC4993420 | biostudies-other | 2016

REPOSITORIES: biostudies-other

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Immune checkpoint inhibitors: the new frontier in non-small-cell lung cancer treatment.

El-Osta Hazem H Shahid Kamran K Mills Glenn M GM Peddi Prakash P

OncoTargets and therapy 20160816

Lung cancer is the major cause for cancer-related death in the US. Although advances in chemotherapy and targeted therapy have improved the outcome of metastatic non-small-cell lung cancer, its prognosis remains dismal. A deeper understanding of the complex interaction between the immune system and tumor microenvironment has identified immune checkpoint inhibitors as new avenue of immunotherapy. Rather than acting directly on the tumor, these therapies work by removing the inhibition exerted by ...[more]

PMID: 27574451

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Project description:BackgroundImmune checkpoint inhibitors (ICIs) for treatment of non-small cell lung cancer (NSCLC) have been rapidly evolving. ICIs are likely to be more effective but also lead to escalating healthcare costs.ObjectivesThe aim of this study was to evaluate the cost effectiveness of immune checkpoint inhibitors (ICIs) for treatment of non-small cell lung cancer (NSCLC).MethodsWe searched the PubMed, Web of Science, and Cochrane Library for studies comparing the cost effectiveness of ICIs for NSCLC. Potential studies identified were independently checked for eligibility by two authors, with disagreement resolved by a third reviewer. Quality of the included studies was evaluated using Consolidated Health Economic Evaluation Reporting Standards checklists.ResultsA total of 22 economic studies were included. Overall reporting of the identified studies largely met CHEERS recommendations. In the first-line setting, for advanced or metastatic NSCLC patients with PD-L1 ≥ 50%, pembrolizumab appeared cost-effective compared with platinum-based chemotherapy in the US and Hong Kong (China), but not in the UK and China. The cost-effectiveness of pembrolizumab versus chemotherapy for first-line treatment of NSCLC in PD-L1 ≥ 1% patients remained obscure. Regardless of PD-L1 expression status, pembrolizumab in combination with chemotherapy could be a cost-effective first-line therapy in the US. On the contrary, addition of atezolizumab to the combination of bevacizumab and chemotherapy was not cost-effective for patients with metastatic non-squamous NSCLC from the US payer perspective. In the second-line setting compared with docetaxel, pembrolizumab was cost-effective; though nivolumab was not cost-effective in the base case, it could be by increased PD-L1 threshold. Results of the cost-effectiveness of atezolizumab second-line treatment remained inconsistent. In addition, the adoption of durvalumab consolidation therapy after chemoradiotherapy could be cost-effective versus no consolidation therapy for patients with stage III NSCLC.ConclusionsImmunotherapy can be a cost-effective option for treatment of NSCLC in several scenarios. A discount of the agents or the use of PD-L1 expression as a biomarker improves the cost-effectiveness of immunotherapy.

Dataset Information

Immune checkpoint inhibitors: the new frontier in non-small-cell lung cancer treatment.

Publications

Immune checkpoint inhibitors: the new frontier in non-small-cell lung cancer treatment.

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