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. 2025 May 21;13(5):e010578.
doi: 10.1136/jitc-2024-010578.

Development and validation of a serum proteomic test for predicting patient outcomes in advanced non-small cell lung cancer treated with atezolizumab or docetaxel

Minu K Srivastava  1 , Wei Zou  2 , Mark McCleland  3 , Joanna Roder  4 , Senait Asmellash  4 , Patrick Norman  4 , Lelia Net  4 , Laura Maguire  4 , Heinrich Roder  4 , Robert Georgantas  4 , David S Shames  3
Affiliations

Development and validation of a serum proteomic test for predicting patient outcomes in advanced non-small cell lung cancer treated with atezolizumab or docetaxel

Minu K Srivastava et al. J Immunother Cancer. .

Abstract

Background: Programmed 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.

Methods: A 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.

Results: Approximately 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.

Conclusions: Aspects 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.

Keywords: Biomarker; Immune Checkpoint Inhibitor; Immunotherapy; Lung Cancer.

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Conflict of interest statement

Competing interests: WZ, MS, and DS are employees of Genentech and hold shares and/or stock options in Roche. MM is a former employee of Genentech. JR, SA, LN, LM, PN, RG, and HR are former employees of Biodesix and hold options or shares therein.

Figures

Figure 1
Figure 1. Consort diagrams for (A) Development, (B) POPLAR, and (C) OAK cohorts.
Figure 2
Figure 2. Heatmap of the log10-transformed feature values from the development cohort clustered by sample and feature. Samples are labeled by their test classification and the features are labeled by their mass/charge location.
Figure 3
Figure 3. Kaplan-Meier plots of OS and PFS by test classification (Good vs Poor) and treatment (A=atezolizumab, D=docetaxel) for the Development cohort (A and B), POPLAR cohort (C and D), and OAK cohort (E and F). OS, overall survival; PFS, progression-free survival.
Figure 4
Figure 4. Kaplan-Meier plots of OS by treatment arm and test classification within PD-L1 defined subgroups of the OAK cohort. (A) TC0 and IC0, (B) TC1/2/3 or IC1/2/3, (C) TC2/3 or IC2/3, (D) TC3 or IC3. (E) Forest plots of OS HRs between test classifications by PD-L1 and treatment subgroup (left) and between treatments by PD-L1 and test classification subgroup (right). A, atezolizumab; D, docetaxel; IC, immune cell; OS, overall survival; PD-L1, programmed cell death-ligand 1; TC, tumor cell.
See this image and copyright information in PMC

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