Immunotherapy and non-small cell lung cancers

Lung cancer is the leading cause of cancer mortality, and non-small cell lung cancer (NSCLC) accounts for more than 85% of all lung cancers. Immunotherapy has brought a paradigm shift to the treatment of NSCLC. Immune checkpoint inhibitors have emerged as one of the main new therapeutic options for patients with advanced NSCLC. This brief review focuses on analyzing the biological rationale and early clinical data available concerning immunotherapeutic strategies, and more specifically, programmed cell death-1 (PD-1) inhibitors and programmed cell death-ligand 1 (PD-L1) inhibitors.

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Pointed Progress in Second-Line Advanced Non–Small-Cell Lung Cancer: The Rapidly Evolving Field of Checkpoint Inhibition

Journal of Clinical Oncology ◽

10.1200/jco.2015.63.8049 ◽

2016 ◽

Vol 34 (14) ◽

pp. 1676-1688 ◽

Cited By ~ 43

Author(s):

Barbara Melosky ◽

Quincy Chu ◽

Rosalyn Juergens ◽

Natasha Leighl ◽

Deanna McLeod ◽

...

Keyword(s):

Lung Cancer ◽

Cell Death ◽

Programmed Cell Death ◽

Randomized Trials ◽

Advanced Nsclc ◽

Checkpoint Inhibitors ◽

Small Cell ◽

Second Line ◽

Small Cell Lung ◽

Cell Death Protein

Purpose Non–small-cell lung cancer (NSCLC) is globally prevalent and associated with high rates of mortality. Immune checkpoint pathways are often exploited by tumors to evade immunity-mediated destruction, and checkpoint inhibitors can reactivate tumor-related immune responses. This review considers available clinical evidence for the use of checkpoint inhibitors in the treatment of second-line advanced NSCLC. Methods Our systematic search revealed 20 clinical trials evaluating checkpoint inhibitors in the second-line setting, three of which were randomized trials comparing programmed cell death protein 1 and programmed death ligand 1 (PD-L1) inhibitors to docetaxel, the current standard of care in this setting. Results A randomized phase II trial comparing the PD-L1 inhibitor atezolizumab to docetaxel did not demonstrate improved survival for atezolizumab in patients overall, although a trend toward improved survival with increased PD-L1 expression was apparent. Twin phase III trials showed significantly improved survival for the programmed cell death protein 1 inhibitor nivolumab compared with docetaxel in patients with both squamous and nonsquamous disease. PD-L1 expression correlated with improved survival in patients with nonsquamous disease, and patients with low levels of PD-L1 expression (< 10%) and those with EGFR mutations are unlikely to benefit. Checkpoint inhibitor therapy is generally well tolerated and associated with low rates of grade 3 or 4 adverse events compared with standard care. Conclusion Level 1 evidence exists to support the use of nivolumab as second-line treatment of patients with squamous advanced NSCLC, as well as in select patients with nonsquamous disease. Benefits remain unknown in patients with targetable driver mutations, and use of PD-L1 expression to guide therapy remains controversial. Results from ongoing randomized trials evaluating biomarkers and other checkpoint inhibitors will further our understanding of this rapidly evolving area of oncology.

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Current landscape of immunotherapy for the treatment of metastatic non-small-cell lung cancer

Current Oncology ◽

10.3747/co.25.3750 ◽

2018 ◽

Vol 25 ◽

pp. 94 ◽

Cited By ~ 24

Author(s):

A. Pabani ◽

C.A. Butts

Keyword(s):

Lung Cancer ◽

Cell Death ◽

Programmed Cell Death ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Advanced Nsclc ◽

Small Cell ◽

Small Cell Lung ◽

Significant Toxicity ◽

Line Setting

For patients with advanced non-small-cell lung cancer (nsclc) lacking a targetable molecular driver, the mainstay of treatment has been cytotoxic chemotherapy. The survival benefit of chemotherapy in this setting is modest and comes with the potential for significant toxicity. The introduction of immunotherapeutic agents targeting the programmed cell death 1 protein (PD-1) and the programmed cell death ligand 1 (PD-L1) has drastically changed the treatment paradigms for these patients. Three agents—atezolizumab, nivolumab, and pembrolizumab—have been shown to be superior to chemotherapy in the second-line setting. For patients with tumours strongly expressing PD-L1, pembrolizumab has been associated with improved outcomes in the first-line setting.Demonstration of the significant benefits of immunotherapy in nsclc has focused attention on new questions. Combination checkpoint regimens, with acceptable toxicity and potentially enhanced efficacy, have been developed, as have combinations of immunotherapy with chemotherapy. In this review, we focus on the published trials that have changed the treatment landscape in advanced nsclc and on the ongoing clinical trials that offer hope to further improve outcomes for patients with advanced nsclc.

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