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

Abstract

9545 Background: Immune checkpoint inhibition (ICI) has improved outcomes for many treatment-naïve advanced non-small cell lung cancer (NSCLC) patients. However, better biomarkers are needed to predict patient response and guide treatment decisions considering added toxicity and higher cost of combination treatments. A prospectively designed, observational study assessed the ability of a clinically validated, blood-based, host immune classifier (HIC) to predict ICI therapy outcomes. Methods: The study (NCT03289780) includes 33 US sites having enrolled over 3,000 NSCLC patients at any stage and line of therapy. All enrolled patients are tested and designated HIC-Hot (HIC-H) or HIC-Cold (HIC-C) prior to therapy initiation. An interim analysis of secondary and exploratory endpoints was performed after 12- 18 months (mo) follow-up with the first 2,000 enrolled patients. We report the overall survival (OS) of HIC-defined subgroups comprising advanced stage (IIIB and higher) NSCLC patients treated with first-line regimens (284 ICI containing treatments, 877 total first-line patients). Results: In a real-world clinical setting, OS of advanced stage NSCLC treatment-naïve patients receiving platinum-based chemotherapy (n = 392) did not differ significantly from patients receiving any type of ICI containing regimen (n = 284); 11.7 mo vs. 14.4 mo; hazard ratio (HR) = 0.94 [95% confidence interval (CI): 0.76–1.17], p = 0.59. HIC-H patients experienced longer survival than HIC-C across multiple regimens, including ICI. For all ICI, median OS (mOS) was not reached for HIC-H (n = 196, CI: 15.4 mo–undefined) vs. 5.0 mo (n = 88, CI: 2.9 mo–6.4 mo) for HIC-C patients (HR = 0.38 [CI: 0.27–0.53], p < 0.0001). Similar results were seen in the ICI only (16.8 mo vs. 2.8 mo; n = 117, HR = 0.36 [CI: 0.22–0.58], p < 0.0001) and ICI/chemotherapy combination subgroups (unreached vs. 6.4 mo; n = 161, HR = 0.41 [CI: 0.26–0.67], p = 0.0003). In the PD-L1 high cohort (PD-L1 ≥50%), mOS for HIC-H was not reached (n = 81, CI: 13.9 mo–undefined) vs. 3.9 mo (n = 41, CI: 2.1 mo–7.8 mo) for HIC-C (HR: 0.39 [CI: 0.24-0.66], p = 0.0003). HIC results were independent of PD-L1 score (p = 0.81) and remained predictive of OS in first-line ICI-treated patients when adjusted for PD-L1 and other covariates by multivariate analysis (HR = 0.40 [CI: 0.28-0.58], p < 0.0001). Conclusions: Blood-based host immune profiling may provide clinically meaningful information for selecting NSCLC patients for two common ICI containing regimens independent of and complementary to PD-L1 score.

Role of mass spectrometry-based serum proteomics signatures in predicting clinical outcomes and toxicity in patients with cancer treated with immunotherapy

“…The HIC test has been validated on samples with traditional platinum-based therapy as well as ICI therapy. 15 As demonstrated in this review, response to immunotherapy in patients can be widely variable; thus, predictive biomarkers that can be used to determine appropriate therapies are crucial. Unfortunately, currently established biomarkers do not always successfully identify patients who have survival benefits from immunotherapy.…”

“…Importantly, in the HIC-Cold group, patients treated with ICI/chemotherapy combination had better overall survival than those treated with ICI monotherapy (ICI/chemotherapy vs ICI monotherapy; Not reached vs 2.5 mo). 15 HIC-Cold status is associated with poor prognosis independent of treatment type and PD-L1 expression. Current treatment guidelines recommend single-agent pembrolizumab for patients with ≥50% PD-L1 expression and pembrolizumab/chemotherapy for patients with PD-L1 expression <50% 28 29 ; however, the data above argue that patients with HIC-Cold status should be given pembrolizumab/chemotherapy even with high PD-L1 expression.…”

“… 24 It has been validated to stratify patients without treatment, 21 as well as those given targeted therapy, 25 chemotherapy, 26 or immunotherapy. 15 27 …”

“…In fact, when examining first-line chemotherapy, immunotherapy, or combination chemotherapy and immunotherapy, HIC stratified all patients effectively when examining overall survival. 15 …”