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The efficacy of immune checkpoint inhibitors in anaplastic lymphoma kinase-positive non-small cell lung cancer

Cited 2 time in Web of Science Cited 2 time in Scopus
Authors
Heo, Ja Yoon; Park, Changhee; Keam, Bhumsuk; Ock, Chan-Young; Kim, Miso; Kim, Tae Min; Kim, Dong-Wan; Kim, Se Hyun; Kim, Yu Jung; Lee, Jong Seok; Heo, Dae Seog
Issue Date
2019-11
Citation
Thoracic Cancer, Vol.10 No.11, pp.2117-2123
Keywords
Anaplastic lymphoma kinaseimmune checkpoint inhibitorsnon-small cell lung cancer
Abstract
Background Despite recent advances in treating non-small cell lung cancer (NSCLC) with immune checkpoint inhibitors (ICIs), their role in ALK-positive NSCLC patients is unclear. We investigated the efficacy of ICIs in patients with ALK-positive NSCLC. Methods Between 2011 and 2018, a total of 14 ALK-positive NSCLC patients treated with ICIs were evaluated retrospectively. Clinicopathologic features including age, PD-L1 expression, and treatment outcomes were analyzed. RNA expression level and cytolytic activity by ALK positivity were analyzed using The Cancer Genome Atlas (TCGA) and National Cancer Center Research Institute (NCCRI) data sets. Results A total of 13 patients (92.9%) received ALK inhibitors. Patients received a median of three (range 2-8) courses of therapy. The study included nine patients (64.3%) who were PD-L1-high (>50%) and four (28.6%) who were PD-L1-low (<50%). The objective response rate was 14.3% (2/14). The median progression-free survival time was 2.18 months (95% confidence interval [CI] 1.13 months-not reached [NR]). The median overall survival time was 5.67 months (95% CI 3.00 months-NR). RNA expression levels of CD274 were similar between the ALK-positive and negative groups in both TCGA and NCCRI datasets. RNA levels of CD8A in both TCGA and NCCRI data sets were nonsignificantly lower in the ALK-positive group. Cytolytic activity scores including interferon-gamma-related response were lower in the ALK-positive group in the NCCRI but not TCGA dataset. Conclusions Despite high PD-L1-positive rates, ICIs show limited efficacy in ALK-positive NSCLC. Decreased interferon-gamma-related response may underlie these findings.
ISSN
1759-7706
URI
https://hdl.handle.net/10371/171819
DOI
https://doi.org/10.1111/1759-7714.13195
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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