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

Authors :
Biagio Ricciuti, MD
Abdul Rafeh Naqash, MD
Jarushka Naidoo, MD
Kartik Sehgal, MD
Adam Miller, MD
Kenneth Kehl, MD, MPH
Deepti Venkatraman, MPH
Jacob Sands, MD
Giuseppe Lamberti, MD
Gonzalo Recondo, MD, PhD
Jiajia Zhang, MD
Shravanti Macherla, MD
Sameer Baig, MD
Paul Walker, MD
Deepa Rangachari, MD
Justin F. Gainor, MD
Daniel B. Costa, MD
Naiyer Rizvi, MD
Lynette M. Sholl, MD
Mizuki Nishino, MD, MPH
Brian Henick, MD
Anna F. Farago, MD, PhD
Mark M. Awad, MD, PhD
Source :
JTO Clinical and Research Reports, Vol 1, Iss 4, Pp 100074- (2020)
Publication Year :
2020
Publisher :
Elsevier, 2020.

Abstract

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 overall 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.

Details

Language :
English
ISSN :
26663643
Volume :
1
Issue :
4
Database :
Directory of Open Access Journals
Journal :
JTO Clinical and Research Reports
Publication Type :
Academic Journal
Accession number :
edsdoj.44c33d5b25fc49e0a525d0f78bde07d6
Document Type :
article
Full Text :
https://doi.org/10.1016/j.jtocrr.2020.100074