ArticleJournal for immunotherapy of cancer2025
Development and validation of a serum proteomic test for predicting patient outcomes in advanced non-small cell lung cancer treated with atezolizumab or docetaxel.
Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundProgrammed cell death-ligand 1 (PD-L1) expression is used in treatment decision-making for patients with advanced non-small cell lung cancer, determining if immune checkpoint inhibitors (ICI) are recommended. Patient selection for ICI treatment can be improved by incorporating the host response. We developed and carried out multiple independent validations of a blood-based test designed to stratify outcomes for patients treated with atezolizumab.
methodsA mass spectrometry-based test was developed from a cohort of patients treated with atezolizumab and validated in two clinical trials (n=269, 823) comparing atezolizumab with docetaxel. The test classifies patients as Good or Poor indicating better or worse outcomes, respectively. The prognostic and predictive power of the test was assessed and evaluated within PD-L1 subgroups. Protein enrichment methods were used to investigate the association of test classification with biological processes.
resultsApproximately 50% of patients were assigned to each classification in all three cohorts. When treated with atezolizumab, the Good subgroup had superior outcomes in all cohorts. Overall survival (OS) HR (95% CI) for Good patients in each cohort was: 0.23 (0.12 to 0.44), 0.32 (0.21 to 0.51), and 0.52 (0.41 to 0.66) and persisted in all PD-L1 subgroups. The test was predictive of differential OS and progression-free survival in one cohort, but not in the other. Enrichment techniques indicated the test was associated with acute inflammatory response, acute phase response, and complement activation.
conclusionsAspects of host immune response to disease can be assessed from the circulating proteome and provide outcome stratification for patients treated with atezolizumab. Combining this information with PD-L1 measurements improves prediction of outcomes.
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