The Impact of Blood Based Host Immune Profile to Identify Aggressive Early Stage NSCLC

Presenting Author(s): Eric Schaefer | Author(s): Paul Walker, R. Brian Mitchell, David Oubre, Nagaprasad Nagajothi, Jiahuai Tan, Mazen Khalil, John Dubay, James Orsini, Wallace Akerley

Introduction
Early detection of non-small cell lung cancer (NSCLC) provides the greatest opportunity for a cure. However, even when NSCLC is identified early, 30-60% of patients diagnosed with stage I-IIIA disease will experience local and/or distant recurrences, respectively. More precise tools are needed to refine lung cancer staging and identify patients that have a more aggressive disease who may benefit from additional treatment or enhanced disease surveillance following curative intent. The Host Immune Classifier (HIC) is a clinically validated, blood-based proteomic test designed to identify an inflammatory disease state associated with aggressive cancer. Here we report the results of a prospectively designed observational study evaluating the ability of the HIC to predict the survival outcomes of patients with early stage NSCLC.

Methods
The INSIGHT study (NCT03289780) has enrolled over 3,500 patients with NSCLC, regardless of stage, at 33 sites throughout the U.S. All subjects are tested and designated HIC-Hot (HIC-H) or HIC-Cold (HIC-C) prior to treatment 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 patients with stage I through stage IIIA (defined by the AJCC seventh edition staging system) NSCLC treated according to standard of care practice.

Results
At the time of database lock, 335 patients with newly diagnosed early stage NSCLC were included in the analysis. Disease stage at study entry was: 20% Stage IA (N=68, 3% HIC-C), 13% Stage IB (N=45, 11% HIC-C), 11% Stage IIA (N=37 (14% HIC-C), 13% Stage IIB (N=44, 21% HIC-C), 32% Stage IIIA (N=141, 34% HIC-C). Without biomarker stratification, landmark 15 mo OS was 85% (95% CI 78-90%) for patients with localized disease (Stage I-IIA) and 73% (95% CI 65-79%) for patients with regional disease (Stage IIB-IIIA), respectively. When patients with localized disease were evaluated with the HIC test, 15 mo landmark OS was significantly decreased for patients classified as HIC-C (HIC-C 55% (95% CI 23-78%) vs. HIC-H 87% (95% CI 80-92%), HR 3.68 (95% CI 1.38-9.87), p value 0.01). Similarly, 15 mo landmark OS for regionally advanced NSCLC was also significantly reduced for patients classified as HIC-C (HIC-C 60% (95% CI 45-72%) vs. HIC-H 79% (95% CI 70-85%), HR 1.77 (95% CI 1.02-3.06), p value 0.04). HIC remained prognostic for OS when adjusted for other covariates such as stage, ECOG performance status, histology, and treatment type in a multivariate analysis (HR of 1.89 (95% CI 1.15-3.12), p value 0.012).

Conclusion
The use of blood-based immune profiling may identify early stage lung cancer patients with aggressive disease that could potentially benefit from enhanced disease surveillance or additional treatment. Furthermore, the inclusion of blood-based biomarkers such as the HIC into the anatomic TNM staging system may help improve prognostication and aid in refining stage classification.