Discontinuation due to immune-related adverse events is a possible predictive factor for immune checkpoint inhibitors in patients with non-small cell lung cancer.
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Drug-Related Side Effects and Adverse Reactions
/ etiology
Female
Follow-Up Studies
Humans
Immunotherapy
/ adverse effects
Lung Diseases, Interstitial
/ chemically induced
Lung Neoplasms
/ drug therapy
Male
Middle Aged
Nivolumab
/ administration & dosage
Prognosis
Retrospective Studies
Survival Rate
Withholding Treatment
Immune checkpoint inhibitor
immune-related adverse event
interstitial lung disease
non-small cell lung cancer
predictive factor
Journal
Thoracic cancer
ISSN: 1759-7714
Titre abrégé: Thorac Cancer
Pays: Singapore
ID NLM: 101531441
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
18
04
2019
revised:
27
06
2019
accepted:
30
06
2019
pubmed:
23
7
2019
medline:
5
8
2020
entrez:
23
7
2019
Statut:
ppublish
Résumé
Immune-related adverse events (irAEs) should be anticipated with treatment by immune checkpoint inhibitors (ICIs). Although the relationship between irAEs and efficacy of ICI has been reported, it has not yet been clarified whether the benefit from ICI outweighs the low frequency of proceeding to subsequent therapies after discontinuation due to irAEs. The study comprised 61 patients with non-small cell lung cancer who underwent treatment with ICIs (nivolumab or pembrolizumab monotherapy) at the Saga University Medical School Hospital from December 2015 to January 2018. Therapeutic effect and progression-free survival (PFS) were compared between the irAEs discontinuation group (AEg) and the group with discontinuation due to all causes other than irAEs (Non-AEg). A total of 30% patients(18/61) had therapy discontinued due to irAEs: 22.5% (9/40) with nivolumab and 42.9% (9/21) with pembrolizumab. The response rate was 50.0% in the AEg and 8.1% in the on-AEg (P = 0.001). The median PFS was significantly longer in the AEg (9.3 months; 95% CI 2.1-12.1) than in the non-AEg (1.9 months; 95% CI 0.9-3.6): HR 0.45 (95%CI 0.20-0.89; log-rank test P = 0.026). The prevalence of drug-induced interstitial lung disease (ILD) was 6.1% (3/49) in cases without interstitial pneumonia (IP) as the underlying disease, whereas it was 50% (6/12) in cases with IP (P = 0.001). Discontinuation of treatment with ICIs due to irAEs predict a good response to ICIs and favorable outcome since their anti-cancer effects continue even after discontinuation. However, the presence of IP as the underlying disease increases the risk of drug-related ILD onset.
Sections du résumé
BACKGROUND
Immune-related adverse events (irAEs) should be anticipated with treatment by immune checkpoint inhibitors (ICIs). Although the relationship between irAEs and efficacy of ICI has been reported, it has not yet been clarified whether the benefit from ICI outweighs the low frequency of proceeding to subsequent therapies after discontinuation due to irAEs.
METHODS
The study comprised 61 patients with non-small cell lung cancer who underwent treatment with ICIs (nivolumab or pembrolizumab monotherapy) at the Saga University Medical School Hospital from December 2015 to January 2018. Therapeutic effect and progression-free survival (PFS) were compared between the irAEs discontinuation group (AEg) and the group with discontinuation due to all causes other than irAEs (Non-AEg).
RESULTS
A total of 30% patients(18/61) had therapy discontinued due to irAEs: 22.5% (9/40) with nivolumab and 42.9% (9/21) with pembrolizumab. The response rate was 50.0% in the AEg and 8.1% in the on-AEg (P = 0.001). The median PFS was significantly longer in the AEg (9.3 months; 95% CI 2.1-12.1) than in the non-AEg (1.9 months; 95% CI 0.9-3.6): HR 0.45 (95%CI 0.20-0.89; log-rank test P = 0.026). The prevalence of drug-induced interstitial lung disease (ILD) was 6.1% (3/49) in cases without interstitial pneumonia (IP) as the underlying disease, whereas it was 50% (6/12) in cases with IP (P = 0.001).
CONCLUSION
Discontinuation of treatment with ICIs due to irAEs predict a good response to ICIs and favorable outcome since their anti-cancer effects continue even after discontinuation. However, the presence of IP as the underlying disease increases the risk of drug-related ILD onset.
Identifiants
pubmed: 31328416
doi: 10.1111/1759-7714.13149
pmc: PMC6718019
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Nivolumab
31YO63LBSN
pembrolizumab
DPT0O3T46P
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1798-1804Informations de copyright
© 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Références
Radiographics. 2000 Sep-Oct;20(5):1245-59
pubmed: 10992015
Lancet. 2003 Jan 11;361(9352):137-9
pubmed: 12531582
N Engl J Med. 2015 Jul 9;373(2):123-35
pubmed: 26028407
N Engl J Med. 2015 Oct 22;373(17):1627-39
pubmed: 26412456
Lancet. 2016 Apr 9;387(10027):1540-1550
pubmed: 26712084
N Engl J Med. 2016 Nov 10;375(19):1823-1833
pubmed: 27718847
Lung Cancer. 2017 Feb;104:111-118
pubmed: 28212992
Chest. 2017 Aug;152(2):271-281
pubmed: 28499515
Lung Cancer. 2017 Sep;111:1-5
pubmed: 28838377
Lung Cancer. 2017 Sep;111:176-181
pubmed: 28838390
Anticancer Res. 2017 Sep;37(9):5199-5205
pubmed: 28870955
Ann Oncol. 2017 Oct 1;28(10):2377-2385
pubmed: 28945858
JAMA Oncol. 2018 Mar 1;4(3):374-378
pubmed: 28975219
Invest New Drugs. 2018 Aug;36(4):638-646
pubmed: 29159766
Lung Cancer. 2017 Oct;112:90-95
pubmed: 29191606
Cancer Immunol Immunother. 2018 Mar;67(3):459-470
pubmed: 29204702
Oncotarget. 2017 May 31;8(57):97671-97682
pubmed: 29228642
Lung Cancer. 2018 Jan;115:71-74
pubmed: 29290265
Lung Cancer. 2018 May;119:14-20
pubmed: 29656747
N Engl J Med. 2018 May 31;378(22):2093-2104
pubmed: 29658845
Thorac Cancer. 2018 Jul;9(7):847-855
pubmed: 29782069
Clin Lung Cancer. 2019 May;20(3):208-214.e2
pubmed: 29803573
Oncologist. 2018 Nov;23(11):1358-1365
pubmed: 29934411
Cancer Immunol Res. 2018 Sep;6(9):1093-1099
pubmed: 29991499