Impact of concomitant medication on clinical outcomes in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors: A retrospective study.
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized
/ administration & dosage
Antineoplastic Agents, Immunological
/ adverse effects
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Drug-Related Side Effects and Adverse Reactions
Female
Humans
Immune Checkpoint Inhibitors
/ administration & dosage
Lung Neoplasms
/ drug therapy
Male
Middle Aged
Nivolumab
/ administration & dosage
Retrospective Studies
concomitant medication
immune checkpoint inhibitors
immune-related adverse events
non-small cell lung cancer
opioids
Journal
Thoracic cancer
ISSN: 1759-7714
Titre abrégé: Thorac Cancer
Pays: Singapore
ID NLM: 101531441
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
revised:
28
04
2021
received:
28
03
2021
accepted:
29
04
2021
pubmed:
15
5
2021
medline:
17
12
2021
entrez:
14
5
2021
Statut:
ppublish
Résumé
It has recently been suggested that concomitant medication may affect the clinical outcome of patients treated with immune checkpoint inhibitors (ICIs). However, only a few studies on the impact of concomitant medication on immune-related adverse events (irAEs) have previously been reported. Here, we aimed to determine the impact of concomitant medication on the efficacy and safety of ICIs. We retrospectively analyzed the data of 300 patients treated with nivolumab or pembrolizumab for advanced non-small cell lung cancer (NSCLC) between January 2016 and July 2018. Multivariate logistic regression analysis was used to assess the effect of concomitant medication on treatment response or irAEs. A multivariate Cox proportional hazards model was used to evaluate concomitant medication-related factors associated with time-to-treatment failure or overall survival (OS). A total of 70 patients responded to treatment and 137 experienced irAEs. The response rate and incidence of irAEs in patients treated with ICIs were not significantly associated with concomitant medication. Multivariate analysis showed that the use of opioids was an independent factor (time-to-treatment failure: hazard ratio 1.39, p = 0.021, OS: hazard ratio 1.54, p = 0.007). The efficacy and safety of nivolumab or pembrolizumab in the treatment of patients with advanced NSCLC were not significantly influenced by concomitant medication. However, opioid usage might be associated with shorter OS in patients treated with these ICIs. Further mechanistic investigations should explore whether these associations are purely prognostic or contribute to ICI resistance.
Sections du résumé
BACKGROUND
It has recently been suggested that concomitant medication may affect the clinical outcome of patients treated with immune checkpoint inhibitors (ICIs). However, only a few studies on the impact of concomitant medication on immune-related adverse events (irAEs) have previously been reported. Here, we aimed to determine the impact of concomitant medication on the efficacy and safety of ICIs.
METHODS
We retrospectively analyzed the data of 300 patients treated with nivolumab or pembrolizumab for advanced non-small cell lung cancer (NSCLC) between January 2016 and July 2018. Multivariate logistic regression analysis was used to assess the effect of concomitant medication on treatment response or irAEs. A multivariate Cox proportional hazards model was used to evaluate concomitant medication-related factors associated with time-to-treatment failure or overall survival (OS).
RESULTS
A total of 70 patients responded to treatment and 137 experienced irAEs. The response rate and incidence of irAEs in patients treated with ICIs were not significantly associated with concomitant medication. Multivariate analysis showed that the use of opioids was an independent factor (time-to-treatment failure: hazard ratio 1.39, p = 0.021, OS: hazard ratio 1.54, p = 0.007).
CONCLUSIONS
The efficacy and safety of nivolumab or pembrolizumab in the treatment of patients with advanced NSCLC were not significantly influenced by concomitant medication. However, opioid usage might be associated with shorter OS in patients treated with these ICIs. Further mechanistic investigations should explore whether these associations are purely prognostic or contribute to ICI resistance.
Identifiants
pubmed: 33990133
doi: 10.1111/1759-7714.14001
pmc: PMC8258365
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Antineoplastic Agents, Immunological
0
Immune Checkpoint Inhibitors
0
Nivolumab
31YO63LBSN
pembrolizumab
DPT0O3T46P
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1983-1994Informations de copyright
© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.
Références
Am J Clin Oncol. 1982 Dec;5(6):649-55
pubmed: 7165009
Anticancer Res. 2018 Aug;38(8):4723-4729
pubmed: 30061241
J Immunother Cancer. 2021 Apr;9(4):
pubmed: 33827906
Lung Cancer Manag. 2019 May 07;8(2):LMT11
pubmed: 31645894
Thorac Cancer. 2019 Mar;10(3):526-532
pubmed: 30666802
J Immunother Cancer. 2018 Jul 2;6(1):64
pubmed: 29966520
Int J Clin Oncol. 2017 Aug;22(4):690-697
pubmed: 28382561
Cancer Sci. 2018 Jan;109(1):54-64
pubmed: 29034589
JAMA Oncol. 2019 Dec 1;5(12):1774-1778
pubmed: 31513236
Oncologist. 2020 Apr;25(4):e679-e683
pubmed: 32297443
Int J Clin Oncol. 2019 Jul;24(7):731-770
pubmed: 31049758
Eur J Cancer. 2020 May;130:155-167
pubmed: 32220780
Thorac Cancer. 2019 Apr;10(4):992-1000
pubmed: 30888716
Eur J Cancer. 2009 Jan;45(2):228-47
pubmed: 19097774
Future Oncol. 2018 Oct;14(23):2415-2431
pubmed: 29978725
Invest New Drugs. 2018 Aug;36(4):638-646
pubmed: 29159766
Target Oncol. 2019 Dec;14(6):707-717
pubmed: 31654203
Clin Transl Oncol. 2020 Sep;22(9):1481-1490
pubmed: 31919759
Thorac Cancer. 2021 Jul;12(13):1983-1994
pubmed: 33990133
Semin Oncol. 2015 Aug;42(4):587-600
pubmed: 26320063
J Clin Oncol. 2018 Jun 10;36(17):1714-1768
pubmed: 29442540
CA Cancer J Clin. 2019 Jan;69(1):7-34
pubmed: 30620402
J Clin Oncol. 2018 Oct 1;36(28):2872-2878
pubmed: 30125216
J Immunother Cancer. 2019 Nov 15;7(1):306
pubmed: 31730012
Ann Oncol. 2020 Apr;31(4):525-531
pubmed: 32115349
Cancer Treat Rev. 2018 Sep;69:21-28
pubmed: 29864718
Cell Mol Life Sci. 2019 Sep;76(17):3383-3406
pubmed: 31087119
Clin Lung Cancer. 2018 Nov;19(6):e861-e864
pubmed: 30172698
J Lipid Res. 2013 Nov;54(11):3106-15
pubmed: 24038316
Nat Immunol. 2015 Aug;16(8):850-8
pubmed: 26075911
Anticancer Res. 2020 Apr;40(4):2209-2217
pubmed: 32234916
Proc Natl Acad Sci U S A. 2017 Jan 31;114(5):E761-E770
pubmed: 28096382
Tumori. 2020 Feb;106(1):55-63
pubmed: 31451071
Br J Pharmacol. 2018 Jul;175(14):2726-2736
pubmed: 28593737
Science. 2018 Jan 5;359(6371):91-97
pubmed: 29097494
Clin Transl Oncol. 2018 Aug;20(8):1072-1079
pubmed: 29368144
Mol Clin Oncol. 2019 Jan;10(1):137-143
pubmed: 30655989
Br J Clin Pharmacol. 2020 Sep;86(9):1778-1789
pubmed: 32543711
J Oncol. 2018 Oct 25;2018:8653489
pubmed: 30498512
Oncology. 2017;92(5):283-290
pubmed: 28222447