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Low Risk of Hyperprogression with First-Line Chemoimmunotherapy for Advanced Non-Small Cell Lung Cancer: Pooled Analysis of 7 Clinical Trials

BACKGROUND: Monotherapy immune checkpoint inhibitor (ICI) used in second- or later-line settings has been reported to induce hyperprogression. This study evaluated hyperprogression risk with ICI (atezolizumab) in the first-, second-, or later-line treatment of advanced non–small cell lung cancer (NS...

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Autores principales: Li, Lee X, Cappuzzo, Federico, Matos, Ignacio, Socinski, Mark A, Hopkins, Ashley M, Sorich, Michael J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10078909/
https://www.ncbi.nlm.nih.gov/pubmed/36905578
http://dx.doi.org/10.1093/oncolo/oyad043
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author Li, Lee X
Cappuzzo, Federico
Matos, Ignacio
Socinski, Mark A
Hopkins, Ashley M
Sorich, Michael J
author_facet Li, Lee X
Cappuzzo, Federico
Matos, Ignacio
Socinski, Mark A
Hopkins, Ashley M
Sorich, Michael J
author_sort Li, Lee X
collection PubMed
description BACKGROUND: Monotherapy immune checkpoint inhibitor (ICI) used in second- or later-line settings has been reported to induce hyperprogression. This study evaluated hyperprogression risk with ICI (atezolizumab) in the first-, second-, or later-line treatment of advanced non–small cell lung cancer (NSCLC), and provides insights into hyperprogression risk with contemporary first-line ICI treatment. METHODS: Hyperprogression was identified using Response Evaluation Criteria in Solid Tumours (RECIST)-based criteria in a dataset of pooled individual-participant level data from BIRCH, FIR, IMpower130, IMpower131, IMpower150, OAK, and POPLAR trials. Odds ratios were computed to compare hyperprogression risks between groups. Landmark Cox proportional-hazard regression was used to evaluate the association between hyperprogression and progression-free survival/overall survival. Secondarily, putative risk factors for hyperprogression among second- or later-line atezolizumab-treated patients were evaluated using univariate logistic regression models. RESULTS: Of the included 4644 patients, 119 of the atezolizumab-treated patients (n = 3129) experienced hyperprogression. Hyperprogression risk was markedly lower with first-line atezolizumab—either chemoimmunotherapy or monotherapy—compared to second/later-line atezolizumab monotherapy (0.7% vs. 8.8%, OR = 0.07, 95% CI, 0.04-0.13). Further, there was no statistically significant difference in hyperprogression risk with first-line atezolizumab-chemoimmunotherapy versus chemotherapy alone (0.6% vs. 1.0%, OR = 0.55, 95% CI, 0.22-1.36). Sensitivity analyses using an extended RECIST-based criteria including early death supported these findings. Hyperprogression was associated with worsened overall survival (HR = 3.4, 95% CI, 2.7-4.2, P < .001); elevated neutrophil-to-lymphocyte ratio was the strongest risk factor for hyperprogression (C-statistic = 0.62, P < .001). CONCLUSIONS: This study presents first evidence for a markedly lower hyperprogression risk in advanced NSCLC patients treated with first-line ICI, particularly with chemoimmunotherapy, as compared to second- or later-line ICI treatment.
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spelling pubmed-100789092023-04-07 Low Risk of Hyperprogression with First-Line Chemoimmunotherapy for Advanced Non-Small Cell Lung Cancer: Pooled Analysis of 7 Clinical Trials Li, Lee X Cappuzzo, Federico Matos, Ignacio Socinski, Mark A Hopkins, Ashley M Sorich, Michael J Oncologist Lung Cancer BACKGROUND: Monotherapy immune checkpoint inhibitor (ICI) used in second- or later-line settings has been reported to induce hyperprogression. This study evaluated hyperprogression risk with ICI (atezolizumab) in the first-, second-, or later-line treatment of advanced non–small cell lung cancer (NSCLC), and provides insights into hyperprogression risk with contemporary first-line ICI treatment. METHODS: Hyperprogression was identified using Response Evaluation Criteria in Solid Tumours (RECIST)-based criteria in a dataset of pooled individual-participant level data from BIRCH, FIR, IMpower130, IMpower131, IMpower150, OAK, and POPLAR trials. Odds ratios were computed to compare hyperprogression risks between groups. Landmark Cox proportional-hazard regression was used to evaluate the association between hyperprogression and progression-free survival/overall survival. Secondarily, putative risk factors for hyperprogression among second- or later-line atezolizumab-treated patients were evaluated using univariate logistic regression models. RESULTS: Of the included 4644 patients, 119 of the atezolizumab-treated patients (n = 3129) experienced hyperprogression. Hyperprogression risk was markedly lower with first-line atezolizumab—either chemoimmunotherapy or monotherapy—compared to second/later-line atezolizumab monotherapy (0.7% vs. 8.8%, OR = 0.07, 95% CI, 0.04-0.13). Further, there was no statistically significant difference in hyperprogression risk with first-line atezolizumab-chemoimmunotherapy versus chemotherapy alone (0.6% vs. 1.0%, OR = 0.55, 95% CI, 0.22-1.36). Sensitivity analyses using an extended RECIST-based criteria including early death supported these findings. Hyperprogression was associated with worsened overall survival (HR = 3.4, 95% CI, 2.7-4.2, P < .001); elevated neutrophil-to-lymphocyte ratio was the strongest risk factor for hyperprogression (C-statistic = 0.62, P < .001). CONCLUSIONS: This study presents first evidence for a markedly lower hyperprogression risk in advanced NSCLC patients treated with first-line ICI, particularly with chemoimmunotherapy, as compared to second- or later-line ICI treatment. Oxford University Press 2023-03-11 /pmc/articles/PMC10078909/ /pubmed/36905578 http://dx.doi.org/10.1093/oncolo/oyad043 Text en © The Author(s) 2023. Published by Oxford University Press. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com.
spellingShingle Lung Cancer
Li, Lee X
Cappuzzo, Federico
Matos, Ignacio
Socinski, Mark A
Hopkins, Ashley M
Sorich, Michael J
Low Risk of Hyperprogression with First-Line Chemoimmunotherapy for Advanced Non-Small Cell Lung Cancer: Pooled Analysis of 7 Clinical Trials
title Low Risk of Hyperprogression with First-Line Chemoimmunotherapy for Advanced Non-Small Cell Lung Cancer: Pooled Analysis of 7 Clinical Trials
title_full Low Risk of Hyperprogression with First-Line Chemoimmunotherapy for Advanced Non-Small Cell Lung Cancer: Pooled Analysis of 7 Clinical Trials
title_fullStr Low Risk of Hyperprogression with First-Line Chemoimmunotherapy for Advanced Non-Small Cell Lung Cancer: Pooled Analysis of 7 Clinical Trials
title_full_unstemmed Low Risk of Hyperprogression with First-Line Chemoimmunotherapy for Advanced Non-Small Cell Lung Cancer: Pooled Analysis of 7 Clinical Trials
title_short Low Risk of Hyperprogression with First-Line Chemoimmunotherapy for Advanced Non-Small Cell Lung Cancer: Pooled Analysis of 7 Clinical Trials
title_sort low risk of hyperprogression with first-line chemoimmunotherapy for advanced non-small cell lung cancer: pooled analysis of 7 clinical trials
topic Lung Cancer
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10078909/
https://www.ncbi.nlm.nih.gov/pubmed/36905578
http://dx.doi.org/10.1093/oncolo/oyad043
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