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Cancer Treat Rev. 2018 Apr;65:65-77. doi: 10.1016/j.ctrv.2018.02.005. Epub 2018 Feb 22.

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

Author information

1
Medical Oncology, BCCA - Vancouver Centre, Vancouver, BC, Canada. Electronic address: BMelosky@bccancer.bc.ca.
2
Cross Cancer Institute and University of Alberta, Edmonton, AB, Canada.
3
McMaster University, Juravinski Cancer Centre, Hamilton, ON, Canada.
4
Princess Margaret Hospital and University of Toronto, Toronto, ON, Canada.
5
BCCA and The University of British Columbia, Vancouver, BC, Canada.
6
Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada.
7
Kaleidoscope Strategic Inc., Toronto, ON, Canada.
8
Montreal General Hospital, Royal Victoria Hospital and McGill University, Montreal, QC, Canada.

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.

KEYWORDS:

Biomarkers; Checkpoint inhibitors; Lung cancer; NSCLC; PD-L1

PMID:
29567557
DOI:
10.1016/j.ctrv.2018.02.005
[Indexed for MEDLINE]

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