Real-world performance of blood-based proteomic profiling in first-line immunotherapy treatment in advanced stage non-small cell lung cancer

Patricia Rich, R Brian Mitchell, Eric Schaefer, Paul R Walker, John W Dubay, Jason Boyd, David Oubre, Ray Page, Mazen Khalil, Suman Sinha, Scott Boniol, Hafez Halawani, Edgardo S Santos, Warren Brenner, James M Orsini, Emily Pauli, Jonathan Goldberg, Andrea Veatch, Mitchell Haut, Bassam Ghabach, Savita Bidyasar, Maria Quejada, Waseemullah Khan, Kan Huang, Linda Traylor, Wallace Akerley, Patricia Rich, R Brian Mitchell, Eric Schaefer, Paul R Walker, John W Dubay, Jason Boyd, David Oubre, Ray Page, Mazen Khalil, Suman Sinha, Scott Boniol, Hafez Halawani, Edgardo S Santos, Warren Brenner, James M Orsini, Emily Pauli, Jonathan Goldberg, Andrea Veatch, Mitchell Haut, Bassam Ghabach, Savita Bidyasar, Maria Quejada, Waseemullah Khan, Kan Huang, Linda Traylor, Wallace Akerley

Abstract

Purpose: Immune checkpoint inhibition (ICI) therapy has improved patient outcomes in advanced non-small cell lung cancer (NSCLC), but better biomarkers are needed. A clinically validated, blood-based proteomic test, or host immune classifier (HIC), was assessed for its ability to predict ICI therapy outcomes in this real-world, prospectively designed, observational study.

Materials and methods: The prospectively designed, observational registry study INSIGHT (Clinical Effectiveness Assessment of VeriStrat® Testing and Validation of Immunotherapy Tests in NSCLC Subjects) (NCT03289780) includes 35 US sites having enrolled over 3570 NSCLC patients at any stage and line of therapy. After enrolment and prior to therapy initiation, all patients are tested and designated HIC-Hot (HIC-H) or HIC-Cold (HIC-C). A prespecified interim analysis was performed after 1-year follow-up with the first 2000 enrolled patients. We report the overall survival (OS) of patients with advanced stage (IIIB and IV) NSCLC treated in the first-line (ICI-containing therapies n=284; all first-line therapies n=877), by treatment type and in HIC-defined subgroups.

Results: OS for HIC-H patients was longer than OS for HIC-C patients across treatment regimens, including ICI. For patients treated with all ICI regimens, median OS was not reached (95% CI 15.4 to undefined months) for HIC-H (n=196) vs 5.0 months (95% CI 2.9 to 6.4) for HIC-C patients (n=88); HR=0.38 (95% CI 0.27 to 0.53), p<0.0001. For ICI monotherapy, OS was 16.8 vs 2.8 months (HR=0.36 (95% CI 0.22 to 0.58), p<0.0001) and for ICI with chemotherapy OS was unreached vs 6.4 months (HR=0.41 (95% CI 0.26 to 0.67), p=0.0003). HIC results were independent of programmed death ligand 1 (PD-L1). In a subgroup with PD-L1 ≥50% and performance status 0-1, HIC stratified survival significantly for ICI monotherapy but not ICI with chemotherapy.

Conclusion: Blood-based HIC proteomic testing provides clinically meaningful information for immunotherapy treatment decision in NSCLC independent of PD-L1. The data suggest that HIC-C patients should not be treated with ICI alone regardless of their PD-L1 expression.

Keywords: biomarkers; immunotherapy; lung neoplasms; tumor.

Conflict of interest statement

Competing interests: PRW: Speaker’s Bureau (Genentech), Consultant (Biodesix), Ownership/stock interest/employment (Circulogene, Theranostics). DO: Speaker’s Bureau (Bayer), Consultant (Coherus, Abbvie), Ownership/stock interest (Karyopham), Honorarium (Daiichi-Sankyo, Rigel), Contracted/supported research grant (Helsinn, MEI, FibroGen). RP: Consultant (AstraZeneca, Tesaro, Amgen, Roche), Honorarium (Cardinal Health), Contracted/supported research grant (E.R. Squibb Sons, Gilead Sciences, Takeda, AstraZeneca, Genentech, Roche, Janssen, Celgene, Lilly). ESS: Speaker’s Bureau (Biodesix; Caris SL; Paradigm Dx; Guardant Health; Genentech; Pfizer; Amgen; Novartis; Boehringer-Ingelheim; Merck; AstraZeneca; Dova; Sanofigenzyme, Oncocyte, Eli Lilly), Consultant (Astra Zeneca, Lilly, BluePrint Medicine, Inivata/Neogenomics). JMO: Speaker’s Bureau (Pfizer-Padcev, Astellas, Xtandi), Advisory Board (Janssen-Zytiga, Pfizer-Padcev). EP: Speaker’s Bureau (TG Therapeutics), Advisory Board (Flatiron Health), Consultant (Eli Lilly; Eisai). BG: Speaker’s Bureau (Boehrenger Ingelheim), Advisory Board (GlaxoSmithKline). LT: Employment (Biodesix). WA: Consultant (Calithera Biosciences, AstraZeneca), Contracted/supported research grant (AstraZeneca, Bristol-Myers Squibb, Loxo).

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Disposition of patients in the study interim analysis. HIC, host immune classifier; ICI, immune checkpoint inhibitor; NSCLC, non-small cell lung cancer.
Figure 2
Figure 2
Kalpan-Meier analysis of overall survival in patients with advanced stage NSCLC. (A) Received platinum-doublet chemotherapy (PTCT) or ICI-containing therapy (ICI) in the first-line setting, and in subsets of patients receiving (B) PTCT and (C) ICI-containing regimen by HIC classification. HIC-C, host immune classifier-cold; HIC-H, HIC-hot; ICI, immune checkpoint inhibition; mOS, median overall survival in months; NR, not reached; NSCLC, non-small cell lung cancer; und, undefined.
Figure 3
Figure 3
Kaplan-Meier analysis of overall survival in patients with advanced stage NSCLC receiving (A, C, E) ICI as monotherapy or (B, D, F) ICI in combination with chemotherapy by (A, B) HIC classification, (C, D) PD-L1 expression (omitting PD-L1 status NA), and (E, F) by HIC classification in the subsets of patients with high PD-L1 expression and ECOG PS 0-1. PD-L1 high, PD-L1 expression ≥50%; PD-L1 low, PD-L1 ≥1% and

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