Association Between Immune-Related Adverse Events and Clinical Outcomes to Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Blockade in SCLC

被引：21

作者：

Ricciuti, Biagio ^{[1
]}

Naqash, Abdul Rafeh ^{[2
]}

Naidoo, Jarushka ^{[3
]}

Sehgal, Kartik ^{[4
]}

Miller, Adam ^{[5
]}

Kehl, Kenneth ^{[1
]}

Venkatraman, Deepti ^{[1
]}

Sands, Jacob ^{[1
]}

Lamberti, Giuseppe ^{[1
]}

Recondo, Gonzalo ^{[1
]}

Zhang, Jiajia ^{[3
]}

Macherla, Shravanti ^{[2
]}

Baig, Sameer ^{[2
]}

Walker, Paul ^{[2
]}

Rangachari, Deepa

Gainor, Justin F. ^{[5
]}

Costa, Daniel B.

Rizvi, Naiyer ^{[6
]}

Sholl, Lynette M. ^{[1
]}

Nishino, Mizuki ^{[1
]}

Henick, Brian ^{[6
]}

Farago, Anna F.

Awad, Mark M. ^{[1
]}

机构：

[1] Harvard Med Sch, Lowe Ctr Thorac Oncol, Dana Farber Canc Inst, 450 Brookline Ave,Dana 1240, Boston, MA 02215 USA

[2] East Carolina Univ, Div Hematol Oncol, Greenville, NC USA

[3] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA

[4] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA USA

[5] Massachusetts Gen Hosp, Dept Med, Boston, MA USA

[6] Columbia Univ, Dept Med, Med Ctr, New York, NY USA

来源：

JTO CLINICAL AND RESEARCH REPORTS | 2020年 / 1卷 / 04期

关键词：

SCLC; irAEs; PD-(L)1; CTLA-4; NIVOLUMAB;

D O I：

10.1016/j.jtocrr.2020.100074

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Introduction: The development of immune-related adverse events (irAEs) has been associated with improved efficacy of immune checkpoint inhibitors in patients with urothelial cancer, melanoma, and NSCLC. Whether this association exists in patients with SCLC is currently unknown.Methods: We conducted a multicenter retrospective study to evaluate the relationship between irAEs and immunotherapy efficacy in SCLC. To account for the lead-time bias resulting from the time-dependent nature of irAEs, the development of irAEs was considered as a time-varying covariate in univariate and multivariate Cox proportional hazard models.Results: Of the 183 patients treated with immunotherapy, 73 (39.9%) experienced at least one irAE. A total of 42 patients (22.9%) had grade 1 to 2 irAEs, whereas 31 patients (16.9%) had grade 3 to 4 irAEs. The median time of onset to the first irAE was 24 days (interquartile range: 14- 55). The baseline clinicopathologic features were well-balanced between patients with and without irAEs. At a median follow-up of 24 months (95% confidence interval [CI]: 17.0-31.6), the median progression-free survival was significantly longer in the irAE group than the non-irAE group (3.8 versus 1.3 mo, p < 0.0001). The median over-all survival was also significantly longer among patients with irAEs than patients without irAEs (13.8 versus 2.9 mo, p < 0.0001). When analyzed as a time-varying covariate, the development of irAEs was associated with a significant improvement in progression-free survival (hazard ratio: 0.44 [95% CI: 0.29-0.66], p < 0.001) and overall survival (hazard ratio: 0.47 [95% CI: 0.32-0.71], p < 0.001) in multivariate models. Conclusions: The development of irAEs is associated with improved clinical outcomes for immunotherapy in patients with advanced SCLC.(c) 2020 The Authors. Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer. This is an open access article under the CC BY-NC-ND li-cense (http://creativecommons.org/licenses/by-nc-nd/ 4.0/).

引用

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