Effect of Systemic Steroid Use for Immune-Related Adverse Events in Patients with Non-Small Cell Lung Cancer Receiving PD-1 Blockade Drugs

被引:21
作者
Mouri, Atsuto [1 ]
Kaira, Kyoichi [1 ]
Yamaguchi, Ou [1 ]
Hashimoto, Kousuke [1 ]
Miura, Yu [1 ]
Shiono, Ayako [1 ]
Shinomiya, Shun [1 ]
Imai, Hisao [1 ]
Kobayashi, Kunihiko [1 ]
Kagamu, Hiroshi [1 ]
机构
[1] Saitama Med Univ, Comprehens Canc Ctr, Int Med Ctr, Dept Resp Med, 1397-1 Yamane, Hidaka, Saitama 3501298, Japan
关键词
steroid; immune-check point inhibitor; immune-related adverse events; non-small cell carcinoma; efficacy; PROGRESSION-FREE SURVIVAL; NIVOLUMAB;
D O I
10.3390/jcm10163744
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objectives: Programmed death-1(PD-1)/programmed death ligand-1 (PD-L1) antibodies have clinical benefits for cancer patients facing immune-related adverse events (irAEs). However, the effect of steroid use on the prognosis of patients with non-small cell lung cancer (NSCLC) receiving PD-1 blockade remains unclear. Methods: NSCLC patients with complete response (CR)/partial response (PR) or stable disease (SD)/not evaluable (NE) status plus progression-free survival (PFS) of 180 days after PD-1 blockade from December 2015 to December 2018 were retrospectively registered in our study and were divided into two groups: those with and without systemic steroid use for irAEs. Results: In total, 126 patients who had benefitted from PD-1 blockade were enrolled in our study; among them, 44 received systemic steroids for irAEs, and 82 had no adverse events or, if they did, did not receive systemic steroids. Among the 44 patients requiring steroids, interstitial lung disease (ILD), adrenal insufficiency, diarrhea, and liver dysfunction were observed in 19, 9, 4, and 4 patients, respectively. More side effects were observed in the group treated by steroids. The median PFS and overall survival (OS) in patients with and without systemic steroid use were 11.7 and 16.0 months (p < 0.037) and 35.0 and 41.0 months (p < 0.28), respectively. In univariate and multivariate analyses of survival, systemic steroid treatment for irAEs was significantly associated with PFS. The occurrence of ILD, adrenal insufficiency, and fever was significant in patients who used systemic steroids for irAEs. Conclusions: Patients administered systemic steroids for irAEs due to PD-1 blockade treatment exhibited shorter PFS than those who were not. Systemic steroids might affect survival after PD-1 blockade even for patients who once acquired its clinical benefit.
引用
收藏
页数:13
相关论文
共 26 条
[1]   Endogenous Glucocorticoid Signaling Regulates CD8+T Cell Differentiation and Development of Dysfunction in the Tumor Microenvironment [J].
Acharya, Nandini ;
Madi, Asaf ;
Zhang, Huiyuan ;
Klapholz, Max ;
Escobar, Giulia ;
Dulberg, Shai ;
Christian, Elena ;
Ferreira, Michelle ;
Dixon, Karen O. ;
Fell, Geoffrey ;
Tooley, Katherine ;
Mangani, Davide ;
Xia, Junrong ;
Singer, Meromit ;
Bosenberg, Marcus ;
Neuberg, Donna ;
Rozenblatt-Rosen, Orit ;
Regev, Aviv ;
Kuchroo, Vijay K. ;
Anderson, Ana C. .
IMMUNITY, 2020, 53 (03) :658-+
[2]   Impact of Baseline Steroids on Efficacy of Programmed Cell Death-1 and Programmed Death-Ligand 1 Blockade in Patients With Non-Small-Cell Lung Cancer [J].
Arbour, Kathryn C. ;
Mezquita, Laura ;
Long, Niamh ;
Rizvi, Hira ;
Auclin, Edouard ;
Ni, Andy ;
Martinez-Bernal, Gala ;
Ferrara, Roberto ;
Lai, W. Victoria ;
Hendriks, Lizza E. L. ;
Sabari, Joshua K. ;
Caramella, Caroline ;
Plodkowski, Andrew J. ;
Halpenny, Darragh ;
Chaft, Jamie E. ;
Planchard, David ;
Riely, Gregory J. ;
Besse, Benjamin ;
Hellmann, Matthew D. .
JOURNAL OF CLINICAL ONCOLOGY, 2018, 36 (28) :2872-+
[3]   Immune regulation by glucocorticoids [J].
Cain, Derek W. ;
Cidlowski, John A. .
NATURE REVIEWS IMMUNOLOGY, 2017, 17 (04) :233-247
[4]   Association of baseline systemic corticosteroid use with overall survival and time to next treatment in patients receiving immune checkpoint inhibitor therapy in real-world US oncology practice for advanced non-small cell lung cancer, melanoma, or urothelial carcinoma [J].
Drakaki, Alexandra ;
Dhillon, Preet K. ;
Wakelee, Heather ;
Chui, Stephen Y. ;
Shim, Jinjoo ;
Kent, Matthew ;
Degaonkar, Viraj ;
Hoang, Tien ;
McNally, Virginia ;
Luhn, Patricia ;
Gutzmer, Ralf .
ONCOIMMUNOLOGY, 2020, 9 (01)
[5]   Clinical factors associated with early progression and grade 3-4 toxicity in patients with advanced non-small-cell lung cancers treated with nivolumab [J].
Dumenil, Coraline ;
Massiani, Marie-Ange ;
Dumoulin, Jennifer ;
Giraud, Violaine ;
Labrune, Sylvie ;
Chinet, Thierry ;
Leprieur, Etienne Giroux .
PLOS ONE, 2018, 13 (04)
[6]   New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1) [J].
Eisenhauer, E. A. ;
Therasse, P. ;
Bogaerts, J. ;
Schwartz, L. H. ;
Sargent, D. ;
Ford, R. ;
Dancey, J. ;
Arbuck, S. ;
Gwyther, S. ;
Mooney, M. ;
Rubinstein, L. ;
Shankar, L. ;
Dodd, L. ;
Kaplan, R. ;
Lacombe, D. ;
Verweij, J. .
EUROPEAN JOURNAL OF CANCER, 2009, 45 (02) :228-247
[7]   Modulation of peripheral blood immune cells by early use of steroids and its association with clinical outcomes in patients with metastatic non-small cell lung cancer treated with immune checkpoint inhibitors [J].
Fuca, Giovanni ;
Galli, Giulia ;
Poggi, Marta ;
Lo Russo, Giuseppe ;
Proto, Claudia ;
Imbimbo, Martina ;
Ferrara, Roberto ;
Zilembo, Nicoletta ;
Ganzinelli, Monica ;
Sica, Antonio ;
Torri, Valter ;
Colombo, Mario Paolo ;
Vernieri, Claudio ;
Balsari, Andrea ;
de Braud, Filippo ;
Garassino, Marina Chiara ;
Signorelli, Diego .
ESMO OPEN, 2019, 4 (01)
[8]   Pembrolizumab plus Chemotherapy in Metastatic Non-Small-Cell Lung Cancer [J].
Gandhi, L. ;
Rodriguez-Abreu, D. ;
Gadgeel, S. ;
Esteban, E. ;
Felip, E. ;
De Angelis, F. ;
Domine, M. ;
Clingan, P. ;
Hochmair, M. J. ;
Powell, S. F. ;
Cheng, S. Y. -S. ;
Bischoff, H. G. ;
Peled, N. ;
Grossi, F. ;
Jennens, R. R. ;
Reck, M. ;
Hui, R. ;
Garon, E. B. ;
Boyer, M. ;
Rubio-Viqueira, B. ;
Novello, S. ;
Kurata, T. ;
Gray, J. E. ;
Vida, J. ;
Wei, Z. ;
Yang, J. ;
Raftopoulos, H. ;
Pietanza, M. C. ;
Garassino, M. C. .
NEW ENGLAND JOURNAL OF MEDICINE, 2018, 378 (22) :2078-2092
[9]  
Grennan Dara, 2019, JAMA, V322, P282, DOI 10.1001/jama.2019.8506
[10]   Association of Immune-Related Adverse Events With Nivolumab Efficacy in Non-Small Cell Lung Cancer [J].
Haratani, Koji ;
Hayashi, Hidetoshi ;
Chiba, Yasutaka ;
Kudo, Keita ;
Yonesaka, Kimio ;
Kato, Ryoji ;
Kaneda, Hiroyasu ;
Hasegawa, Yoshikazu ;
Tanaka, Kaoru ;
Takeda, Masayuki ;
Nakagawa, Kazuhiko .
JAMA ONCOLOGY, 2018, 4 (03) :374-378