Breaking the biomarker code: PD-L1 expression and checkpoint inhibition in advanced NSCLC. (April 2018)

• Record Type: Journal Article
• Authors: Melosky, B.; Chu, Q.; Juergens, R.A.; Leighl, N.; Ionescu, D.; Tsao, M.-S.; McLeod, D.; Hirsh, V.
• Is Part Of: Cancer treatment reviews. Volume 65(2018)
• Page Start: 65
• Page End: 77
• Publication Date: 2018-04
• Subjects: Lung cancer -- NSCLC -- Checkpoint inhibitors -- Biomarkers -- PD-L1; Cancer -- Periodicals; Cancer -- Treatment -- Periodicals; Neoplasms -- therapy -- Periodicals; Cancer -- Périodiques; Cancer -- Traitement -- Périodiques; Cancer -- Treatment; Electronic journals; Periodicals; 616.99406
• DOI: 10.1016/j.ctrv.2018.02.005
• Languages: English
• ISSNs: 0305-7372

Abstract

Highlights: Checkpoint inhibitors re-engage the immune system to fight cancer. Survival benefits are confirmed for first- and later line advanced NSCLC. Immune-related adverse events with checkpoint inhibitors are tolerable. PD-L1 biomarker status can inform treatment decisions. Agent-specific PD-L1 tests should be used until methods are standardized. Abstract: Background: Lung cancer is the most common cause of cancer-related death among males and the second leading cause among females globally. Checkpoint inhibitors re-engage the immune system to fight cancer. This review evaluates phase III data on the use of checkpoint inhibitors in the treatment of advanced NSCLC and addresses PD-L1 expression in predicting efficacy. Methods: Six phase III clinical trials investigating checkpoint inhibitors for NSCLC were identified through a search of PubMed (to November 15, 2016) and conference databases, with findings updated from a directed search of eligible studies conducted in January 2018. Results: Significant reductions in the risk of death ranging from 27% to 41% and were observed second-line and beyond. A relationship between PD-L1 expression and survival was apparent in most trials with optimal benefit for the highest expression levels (≥50%). Benefit was also observed at low or no PD-L1 expression levels and in third-line in some studies. Significantly improved PFS was observed for pembrolizumab at high PD-L1 expression levels (≥50%) first-line. Immune-related adverse events associated with checkpoint inhibitors are tolerable and rates of pneumonitis may be lower among PD-L1 inhibitors. Use of checkpoint inhibitors for tumors with driver mutations should only be considered after all appropriate targeted therapy and chemotherapy have been exhausted. PD-L1 testing presents a valuable tool to guide treatment sequencing and we recommend use of agent-specific PD-L1 tests and respective scoring systems until a standardized, convenient and broadly applicable test is identified. Conclusions: Checkpoint inhibitors represent a major advance in the treatment of advanced NSCLC and PD-L1 status can inform treatment decisions.