Immune-Related Adverse Events and Corticosteroid Use for Cancer-Related Symptoms Are Associated With Efficacy in Patients With Non-small Cell Lung Cancer Receiving Anti-PD-(L)1 Blockade Agents

被引:52
作者
Riudavets, Mariona [1 ,2 ]
Mosquera, Joaquin [3 ]
Garcia-Campelo, Rosario [3 ]
Serra, Jorgina [1 ]
Anguera, Georgia [1 ]
Gallardo, Pablo [1 ]
Sullivan, Ivana [1 ]
Barba, Andres [1 ]
del Carpio, Luis [1 ]
Barnadas, Agusti [1 ]
Gich, Ignasi [4 ,5 ,6 ]
Majem, Margarita [1 ]
机构
[1] Hosp Santa Creu & Sant Pau, Dept Med Oncol, Barcelona, Spain
[2] Univ Autonoma Barcelona UAB, Dept Med, Barcelona, Spain
[3] Hosp Univ A Coruna, Dept Med Oncol, La Coruna, Spain
[4] Hosp Santa Creu & Sant Pau, Dept Clin Epidemiol & Publ Hlth, Barcelona, Spain
[5] CIBER Epidemiol & Salud Publ CIBERESP, Madrid, Spain
[6] St Pau Biomed Res Inst IIB St Pau, Barcelona, Spain
关键词
immune-related adverse events; immunotherapy; advanced NSCLC; corticosteroids; efficacy; OPEN-LABEL; NIVOLUMAB; DOCETAXEL; PEMBROLIZUMAB;
D O I
10.3389/fonc.2020.01677
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background:Immune-related adverse events (irAEs) have been associated with improved efficacy in advanced non-small cell lung cancer (NSCLC) patients receiving anti-PD-(L)1 blockade agents, while the concurrent use of corticosteroids seems to worsen it. We evaluated outcomes in advanced NSCLC patients treated with anti-PD-(L)1 blockade agents in relation to the presence of irAEs and the reasons for using corticosteroids: whether for palliative cancer-related reasons or for the management of irAEs. Methods:Clinical outcomes in advanced NSCLC patients treated with anti-PD-(L)1 blockade agents were calculated with regard to the presence of irAEs and the use of corticosteroids. A landmark analysis was performed to avoid immortal time bias due to the time-dependent nature of irAEs. Results:Out of a total of 267 patients, the 56.9% of patients who experienced irAEs had significantly improved outcomes. In the landmark analysis, median progression-free survival (PFS) was 12.4 months for patients with irAEs vs. 4.1 months for patients without irAEs (p< 0.001), while median overall survival (OS) was 28.2 vs. 12.5 months, respectively (p< 0.001). Likewise, objective response and disease control rates were significantly higher in patients experiencing irAEs: 48.6 vs. 22.8% and 77.1 vs. 39.6% (p< 0.001), respectively. Median OS was significantly shorter for patients receiving >= 10 mg of prednisone equivalent daily for cancer-related symptoms than for the rest of patients (<10 mg prednisone equivalent daily or for management of irAEs): 6 vs. 15.9 months (p< 0.001). Conclusions:IrAEs were associated with improved efficacy in advanced NSCLC patients when a landmark analysis was applied. Patients receiving corticosteroids had significantly poorer outcomes when they were used for cancer-related symptoms.
引用
收藏
页数:11
相关论文
共 35 条
[11]   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
[12]   Concomitant use of corticosteroids and immune checkpoint inhibitors in patients with hematologic or solid neoplasms: A systematic review [J].
Garant, A. ;
Guilbault, C. ;
Ekmekjian, T. ;
Greenwald, Z. ;
Murgoi, P. ;
Vuong, T. .
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, 2017, 120 :86-92
[13]   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
[14]  
HASANALI O, 2016, ONCOIMMUNOLOGY, V5
[15]   Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden [J].
Hellmann, M. D. ;
Ciuleanu, T. -E. ;
Pluzanski, A. ;
Lee, J. S. ;
Otterson, G. A. ;
Audigier-Valette, C. ;
Minenza, E. ;
Linardou, H. ;
Burgers, S. ;
Salman, P. ;
Borghaei, H. ;
Ramalingam, S. S. ;
Brahmer, J. ;
Reck, M. ;
O'Byrne, K. J. ;
Geese, W. J. ;
Green, G. ;
Chang, H. ;
Szustakowski, J. ;
Bhagavatheeswaran, P. ;
Healey, D. ;
Fu, Y. ;
Nathan, F. ;
Paz-Ares, L. .
NEW ENGLAND JOURNAL OF MEDICINE, 2018, 378 (22) :2093-2104
[16]   Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial [J].
Hodi, Frank Stephen ;
Chiarion-Sileni, Vanna ;
Gonzalez, Rene ;
Grob, Jean-Jacques ;
Rutkowski, Piotr ;
Cowey, Charles Lance ;
Lao, Christopher D. ;
Schadendorf, Dirk ;
Wagstaff, John ;
Dummer, Reinhard ;
Ferrucci, Pier Francesco ;
Smylie, Michael ;
Hill, Andrew ;
Hogg, David ;
Marquez-Rodas, Ivan ;
Jiang, Joel ;
Rizzo, Jasmine ;
Larkin, James ;
Wolchok, Jedd D. .
LANCET ONCOLOGY, 2018, 19 (11) :1480-1492
[17]   Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study [J].
Langer, Corey J. ;
Gadgeel, Shirish M. ;
Borghaei, Hossein ;
Papadimitrakopoulou, Vassiliki A. ;
Patnaik, Amita ;
Powell, Steven F. ;
Gentzler, Ryan D. ;
Martins, Renato G. ;
Stevenson, James P. ;
Jalal, Shadia I. ;
Panwalkar, Amit ;
Yang, James Chih-Hsin ;
Gubens, Matthew ;
Sequist, Lecia V. ;
Awad, Mark M. ;
Fiore, Joseph ;
Ge, Yang ;
Raftopoulos, Harry ;
Gandhi, Leena .
LANCET ONCOLOGY, 2016, 17 (11) :1497-1508
[18]   Treatment-Related Adverse Events Predict Improved Clinical Outcome in NSCLC Patients on KEYNOTE-001 at a Single Center [J].
Lisberg, Aaron ;
Tucker, D. Andrew ;
Goldman, Jonathan W. ;
Wolf, Brian ;
Carroll, James ;
Hardy, Ariana ;
Morris, Karolyn ;
Linares, Paulina ;
Adame, Carlos ;
Spiegel, Marshall L. ;
Wells, Courtney ;
McKenzie, Jordan ;
Ledezma, Blanca ;
Mendenhall, Melody ;
Abarca, Phillip ;
Bornazyan, Krikor ;
Hunt, Jaime ;
Moghadam, Nima ;
Chong, Natalie ;
Nameth, Danielle ;
Marx, Caitlin ;
Madrigal, John ;
Vangala, Sitaram ;
Shaverdian, Narek ;
Elashoff, David ;
Garon, Edward B. .
CANCER IMMUNOLOGY RESEARCH, 2018, 6 (03) :288-294
[19]   Immune Checkpoint Blockade [J].
Naidoo, Jarushka ;
Page, David B. ;
Wolchok, Jedd D. .
HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA, 2014, 28 (03) :585-+
[20]   Efficacy and safety of two doses of pemetrexed supplemented with folic acid and vitamin B12 in previously treated patients with non-small cell lung cancer [J].
Ohe, Yuichiro ;
Ichinose, Yukito ;
Nakagawa, Kazuhiko ;
Tamura, Tomohicle ;
Kubota, Kaoru ;
Yamamoto, Nobuyuki ;
Adachi, Susumu ;
Nambu, Yoshihiro ;
Fujimoto, Toshio ;
Nishiwaki, Yutaka ;
Saijo, Nagahiro ;
Fukuoka, Masahiro .
CLINICAL CANCER RESEARCH, 2008, 14 (13) :4206-4212