Efficacy and safety of programmed cell death receptor 1 inhibition-based regimens in patients with pediatric malignancies: the real-world study in China.
PD-1 inhibitor-based treatment
PD-1 inhibitors
efficacy
pediatric malignancies
safety
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2023
2023
Historique:
received:
09
03
2023
accepted:
29
05
2023
medline:
28
6
2023
pubmed:
26
6
2023
entrez:
26
6
2023
Statut:
epublish
Résumé
Programmed death receptor 1 (PD-1) inhibition has shown durable response and mild adverse events (AEs) in adult malignancies. However, data on the clinical activity of PD-1 inhibition in pediatric patients are lacking. We comprehensively assessed the efficacy and safety of PD-1 inhibitor-based regimens for pediatric malignancies. We conducted a real-world, multi-institutional, retrospective analysis of pediatric malignancies treated with PD-1 inhibitor-based regimens. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS). The secondary endpoints included disease control rate (DCR), duration of response (DOR), and AEs. The Kaplan-Meier method was used to calculate PFS and DOR. The National Cancer Institute Common Toxicity Criteria for AEs (version 5.0) were used to grade toxicity. A total of 93 and 109 patients were evaluated for efficacy and safety, respectively. For all efficacy-evaluable patients, PD-1 inhibitor monotherapy, combined chemotherapy, combined histone deacetylase inhibitor, and combined vascular endothelial growth factor receptor tyrosine kinase inhibitor cohorts, the ORR and DCR were 53.76%/81.72%, 56.67%/83.33%, 54.00%/80.00%, 100.00%/100.00%, and 12.50%/75.00%, respectively; the median PFS and DOR were 17.6/31.2 months, not achieved/not achieved, 14.9/31.2 months, 17.6/14.9 months, and 3.7/1.8 months, respectively; the incidence rate of AEs were 83.49%, 55.26%, 100.00%, 80.00%, and 100.00%, respectively. One patient in the PD-1 inhibitor-combined chemotherapy cohort discontinued treatment due to diabetic ketoacidosis. This largest retrospective analysis demonstrate that PD-1 inhibitor-based regimens are potentially effective and tolerable in pediatric malignancies. Our findings provide references for future clinical trials and practice of PD-1 inhibitors in pediatric cancer patients.
Sections du résumé
Background
Programmed death receptor 1 (PD-1) inhibition has shown durable response and mild adverse events (AEs) in adult malignancies. However, data on the clinical activity of PD-1 inhibition in pediatric patients are lacking. We comprehensively assessed the efficacy and safety of PD-1 inhibitor-based regimens for pediatric malignancies.
Methods
We conducted a real-world, multi-institutional, retrospective analysis of pediatric malignancies treated with PD-1 inhibitor-based regimens. The primary endpoints were objective response rate (ORR) and progression-free survival (PFS). The secondary endpoints included disease control rate (DCR), duration of response (DOR), and AEs. The Kaplan-Meier method was used to calculate PFS and DOR. The National Cancer Institute Common Toxicity Criteria for AEs (version 5.0) were used to grade toxicity.
Results
A total of 93 and 109 patients were evaluated for efficacy and safety, respectively. For all efficacy-evaluable patients, PD-1 inhibitor monotherapy, combined chemotherapy, combined histone deacetylase inhibitor, and combined vascular endothelial growth factor receptor tyrosine kinase inhibitor cohorts, the ORR and DCR were 53.76%/81.72%, 56.67%/83.33%, 54.00%/80.00%, 100.00%/100.00%, and 12.50%/75.00%, respectively; the median PFS and DOR were 17.6/31.2 months, not achieved/not achieved, 14.9/31.2 months, 17.6/14.9 months, and 3.7/1.8 months, respectively; the incidence rate of AEs were 83.49%, 55.26%, 100.00%, 80.00%, and 100.00%, respectively. One patient in the PD-1 inhibitor-combined chemotherapy cohort discontinued treatment due to diabetic ketoacidosis.
Conclusions
This largest retrospective analysis demonstrate that PD-1 inhibitor-based regimens are potentially effective and tolerable in pediatric malignancies. Our findings provide references for future clinical trials and practice of PD-1 inhibitors in pediatric cancer patients.
Identifiants
pubmed: 37359533
doi: 10.3389/fimmu.2023.1182751
pmc: PMC10288191
doi:
Substances chimiques
Immune Checkpoint Inhibitors
0
Programmed Cell Death 1 Receptor
0
Vascular Endothelial Growth Factor A
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1182751Informations de copyright
Copyright © 2023 Hong, Song, Lan, Wang, Lu, Zhang, Zhu, Sun, Huang, Liu, Xu, Wu, Guo, Cai, Zhen, Que and Zhang.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.-
Références
Cancer. 2020 Nov 15;126(22):4867-4877
pubmed: 32914866
Acta Oncol. 2001;40(1):44-9
pubmed: 11321659
CA Cancer J Clin. 2022 Jan;72(1):7-33
pubmed: 35020204
Lancet Oncol. 2019 Nov;20(11):1566-1575
pubmed: 31562043
Blood. 2020 Dec 10;136(24):2754-2763
pubmed: 32766875
Lancet. 2021 Sep 11;398(10304):1002-1014
pubmed: 34509219
J Clin Oncol. 2021 Mar 20;39(9):1029-1039
pubmed: 33529058
Lancet Oncol. 2020 Jan;21(1):134-144
pubmed: 31780255
J Immunother Cancer. 2021 Sep;9(9):
pubmed: 34583971
Cancer Immunol Immunother. 2020 Dec;69(12):2523-2532
pubmed: 32577817
Cancer Immunol Immunother. 2019 Sep;68(9):1467-1477
pubmed: 31451841
Sci Rep. 2019 Apr 16;9(1):6136
pubmed: 30992475
Clin Cancer Res. 2022 Dec 1;28(23):5088-5097
pubmed: 36190525
Diabet Med. 2019 Sep;36(9):1075-1081
pubmed: 31199005
Blood. 2017 Jul 20;130(3):267-270
pubmed: 28490569
J Clin Endocrinol Metab. 2018 Sep 1;103(9):3144-3154
pubmed: 29955867
Nat Rev Clin Oncol. 2018 May;15(5):325-340
pubmed: 29508855
Ann Acad Med Singap. 2010 Jan;39(1):43-8
pubmed: 20126814
Lancet Oncol. 2021 Sep;22(9):1265-1274
pubmed: 34391508
Oncologist. 2016 Oct;21(10):1230-1240
pubmed: 27401894
Acta Obstet Gynecol Scand. 2022 Jan;101(1):84-93
pubmed: 34783360
Eur J Cancer. 2020 Aug;135:89-97
pubmed: 32554315
Eur J Cancer. 2021 Jun;150:53-62
pubmed: 33892407
Lancet Oncol. 2020 Apr;21(4):541-550
pubmed: 32192573
Oncologist. 2017 Apr;22(4):470-479
pubmed: 28275115
J Clin Oncol. 2019 Mar 1;37(7):537-546
pubmed: 30620668
Lancet Oncol. 2018 Aug;19(8):1061-1071
pubmed: 29941280
Mol Cancer. 2019 Mar 30;18(1):60
pubmed: 30925919
J Oncol Pharm Pract. 2019 Sep;25(6):1343-1348
pubmed: 30080131
Cancer Commun (Lond). 2022 Jan;42(1):56-59
pubmed: 34918497
Front Pharmacol. 2017 Feb 08;8:49
pubmed: 28228726
Lancet. 2022 Sep 24;400(10357):1020-1032
pubmed: 36154677
Clin Cancer Res. 2015 Oct 1;21(19):4286-93
pubmed: 25977344
Immunotherapy. 2017 Sep;9(12):955-961
pubmed: 28971752
Nat Rev Clin Oncol. 2022 Mar;19(3):151-172
pubmed: 34764464
Ann Oncol. 2015 Dec;26(12):2375-91
pubmed: 26371282
Lancet Oncol. 2020 Jan;21(1):121-133
pubmed: 31812554
Signal Transduct Target Ther. 2021 Oct 27;6(1):365
pubmed: 34702811
Nat Med. 2022 Jan;28(1):125-135
pubmed: 34992263
J Clin Oncol. 2010 Jul 1;28(19):3167-75
pubmed: 20516446
J Korean Med Sci. 2018 Sep 07;33(41):e260
pubmed: 30288158