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Predicting Survival in Patients with Advanced NSCLC Treated with Atezolizumab Using Pre- and on-Treatment Prognostic Biomarkers.

Authors :
Benzekry S
Karlsen M
Bigarré C
Kaoutari AE
Gomes B
Stern M
Neubert A
Bruno R
Mercier F
Vatakuti S
Curle P
Jamois C
Source :
Clinical pharmacology and therapeutics [Clin Pharmacol Ther] 2024 Oct; Vol. 116 (4), pp. 1110-1120. Date of Electronic Publication: 2024 Jul 12.
Publication Year :
2024

Abstract

Existing survival prediction models rely only on baseline or tumor kinetics data and lack machine learning integration. We introduce a novel kinetics-machine learning (kML) model that integrates baseline markers, tumor kinetics, and four on-treatment simple blood markers (albumin, C-reactive protein, lactate dehydrogenase, and neutrophils). Developed for immune-checkpoint inhibition (ICI) in non-small cell lung cancer on three phase II trials (533 patients), kML was validated on the two arms of a phase III trial (ICI and chemotherapy, 377 and 354 patients). It outperformed the current state-of-the-art for individual predictions with a test set C-index of 0.790, 12-months survival accuracy of 78.7% and hazard ratio of 25.2 (95% CI: 10.4-61.3, P < 0.0001) to identify long-term survivors. Critically, kML predicted the success of the phase III trial using only 25 weeks of on-study data (predicted HR = 0.814 (0.64-0.994) vs. final study HR = 0.778 (0.65-0.931)). Modeling on-treatment blood markers combined with predictive machine learning constitutes a valuable approach to support personalized medicine and drug development. The code is publicly available at https://gitlab.inria.fr/benzekry/nlml_onco.<br /> (© 2024 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Details

Language :
English
ISSN :
1532-6535
Volume :
116
Issue :
4
Database :
MEDLINE
Journal :
Clinical pharmacology and therapeutics
Publication Type :
Academic Journal
Accession number :
39001619
Full Text :
https://doi.org/10.1002/cpt.3371