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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
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474257/ https://www.ncbi.nlm.nih.gov/pubmed/34589955 http://dx.doi.org/10.1016/j.jtocrr.2020.100074 |
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author | Ricciuti, Biagio Naqash, Abdul Rafeh Naidoo, Jarushka Sehgal, Kartik Miller, Adam Kehl, Kenneth Venkatraman, Deepti Sands, Jacob Lamberti, Giuseppe Recondo, Gonzalo Zhang, Jiajia Macherla, Shravanti Baig, Sameer Walker, Paul Rangachari, Deepa Gainor, Justin F. Costa, Daniel B. Rizvi, Naiyer Sholl, Lynette M. Nishino, Mizuki Henick, Brian Farago, Anna F. Awad, Mark M. |
author_facet | Ricciuti, Biagio Naqash, Abdul Rafeh Naidoo, Jarushka Sehgal, Kartik Miller, Adam Kehl, Kenneth Venkatraman, Deepti Sands, Jacob Lamberti, Giuseppe Recondo, Gonzalo Zhang, Jiajia Macherla, Shravanti Baig, Sameer Walker, Paul Rangachari, Deepa Gainor, Justin F. Costa, Daniel B. Rizvi, Naiyer Sholl, Lynette M. Nishino, Mizuki Henick, Brian Farago, Anna F. Awad, Mark M. |
author_sort | Ricciuti, Biagio |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8474257 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-84742572021-09-28 Association Between Immune-Related Adverse Events and Clinical Outcomes to Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Blockade in SCLC Ricciuti, Biagio Naqash, Abdul Rafeh Naidoo, Jarushka Sehgal, Kartik Miller, Adam Kehl, Kenneth Venkatraman, Deepti Sands, Jacob Lamberti, Giuseppe Recondo, Gonzalo Zhang, Jiajia Macherla, Shravanti Baig, Sameer Walker, Paul Rangachari, Deepa Gainor, Justin F. Costa, Daniel B. Rizvi, Naiyer Sholl, Lynette M. Nishino, Mizuki Henick, Brian Farago, Anna F. Awad, Mark M. JTO Clin Res Rep Original Article 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. Elsevier 2020-07-15 /pmc/articles/PMC8474257/ /pubmed/34589955 http://dx.doi.org/10.1016/j.jtocrr.2020.100074 Text en © 2020 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Ricciuti, Biagio Naqash, Abdul Rafeh Naidoo, Jarushka Sehgal, Kartik Miller, Adam Kehl, Kenneth Venkatraman, Deepti Sands, Jacob Lamberti, Giuseppe Recondo, Gonzalo Zhang, Jiajia Macherla, Shravanti Baig, Sameer Walker, Paul Rangachari, Deepa Gainor, Justin F. Costa, Daniel B. Rizvi, Naiyer Sholl, Lynette M. Nishino, Mizuki Henick, Brian Farago, Anna F. Awad, Mark M. Association Between Immune-Related Adverse Events and Clinical Outcomes to Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Blockade in SCLC |
title | Association Between Immune-Related Adverse Events and Clinical Outcomes to Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Blockade in SCLC |
title_full | Association Between Immune-Related Adverse Events and Clinical Outcomes to Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Blockade in SCLC |
title_fullStr | Association Between Immune-Related Adverse Events and Clinical Outcomes to Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Blockade in SCLC |
title_full_unstemmed | Association Between Immune-Related Adverse Events and Clinical Outcomes to Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Blockade in SCLC |
title_short | Association Between Immune-Related Adverse Events and Clinical Outcomes to Programmed Cell Death Protein 1/Programmed Death-Ligand 1 Blockade in SCLC |
title_sort | association between immune-related adverse events and clinical outcomes to programmed cell death protein 1/programmed death-ligand 1 blockade in sclc |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8474257/ https://www.ncbi.nlm.nih.gov/pubmed/34589955 http://dx.doi.org/10.1016/j.jtocrr.2020.100074 |
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