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

PurposeImmune 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 methodsThe 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.ResultsOS 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.ConclusionBlood-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.

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Influence of Performance Status on the Effectiveness of Pembrolizumab Monotherapy in First-Line for Advanced Non-Small-Cell Lung Cancer: Results in a Real-World Population

Biology ◽

10.3390/biology10090890 ◽

2021 ◽

Vol 10 (9) ◽

pp. 890

Author(s):

Rocío Jiménez Jiménez Galán ◽

Elena Prado-Mel ◽

María Antonia Pérez-Moreno ◽

Estefanía Caballano-Infantes ◽

Sandra Flores Moreno

Keyword(s):

Lung Cancer ◽

Clinical Trial ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Real World ◽

Performance Status ◽

Small Cell ◽

Small Cell Lung ◽

First Line ◽

Ecog Ps

The KEYNOTE-024 clinical trial showed promising results for pembrolizumab in the first-line of treatment of advanced non-small-cell lung cancer (NSCLC). However, the profile of patients in real-world practice differs from those included in this clinical trial. Here, an observational single-center retrospective study was performed through a comparative analysis of clinical outcomes after pembrolizumab therapy according to the Eastern Cooperative Oncology Group Stage Performance Status (ECOG PS). Moreover, univariate and multivariate analyses were carried out to detect prognostic factors. In our cohort, 63.7% of patients had an ECOG PS of 0–1. Regarding response rate, 31.8% of patients had a partial response (PR), 19.3% had stable disease (SD) and 23.9% had progression disease. On the other hand, patients with ECOG PS ≥ 2 showed a significantly lower rate of PR and SD to pembrolizumab than patients with a PS of 0–1. The rate of response, median overall survival (OS) and progression-free survival (PFS) were significantly higher in patients with ECOG PS 0–1 than in those with ECOG PS ≥ 2. In the current study, we found ECOG PS as the only independent predictor of OS and PFS. Due to the ECOG PS scale being a subjective parameter, other tools are needed to identify treatment effectiveness to each patient.

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Survival among advanced non-small cell lung cancer patients with poor performance status after first-line chemotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.e18144 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. e18144-e18144

Author(s):

Ramzi George Salloum ◽

Thomas J Smith ◽

Gail Jensen ◽

Jennifer Elston-Lafata

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Performance Status ◽

Small Cell ◽

Advanced Stage ◽

Small Cell Lung ◽

First Line ◽

Factors Associated ◽

Line Chemotherapy

e18144 Background: Evidence-based guidelines recommend chemotherapy for medically fit patients with advanced stage non-small cell lung cancer (NSCLC). Performance status (PS) is a commonly used factor in determining the appropriateness for chemotherapy for this group of patients.The prevalence of poor PS and impact of chemotherapy on survival among NSCLC patients has not been studied in community populations. Methods: Insured patients, aged 50+ years, diagnosed with advanced stage NSCLC between 2000 and 2007 were identified via tumor registry (n=292) and linked to medical record abstracted PS, automated medical claims, and Census tract information. A multivariate Cox proportional hazards model was used to determine the factors associated with survival. Tests of statistical significance were two sided. We defined PS 3 or 4 as “poor” since the NCCN and ASCO guidelines agree that those patients should not routinely receive chemotherapy. Results: Of 292 stage IIIB-IV patients, 82 (28%) had PS 3 or 4, and 39% of PS 3-4 patients received first line chemotherapy. Those who received chemotherapy lived 4.8 months compared to 2.4 months for those who did not. Factors associated with a reduced likelihood of death included receipt of chemotherapy (hazard ratio [HR], 0.67) and surgery (HR, 0.27), and female gender (HR, 0.69). Conclusions: In advanced stage NSCLC, poor PS is common, and oncologists are treating about 40% of those patients with the same drugs as for PS 0-2. Modern chemotherapy is associated with positive effects on survival for poor PS patients, as for good PS patients, but we cannot tell if this is due to chemotherapy or some other factor. Further trials, especially randomized trials, in this common but neglected subgroup are indicated.

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