Abstract
<div>AbstractPurpose:<p>Immune checkpoint inhibitors (ICI) are a significant advance to the treatment of advanced non–small cell lung cancer (NSCLC); however, their initiation is associated with heterogeneity in outcomes. This study aimed to develop and validate a prognostic tool of survival in patients with advanced NSCLC treated with ICIs.</p>Experimental Design:<p>A pretreatment prognostic model was developed and validated using clinicopathologic data. Development data consisted of patients with advanced NSCLC treated with atezolizumab from the randomised trials OAK and POPLAR (<i>n</i> = 751). Data from the single-arm atezolizumab trials BIRCH and FIR (<i>n</i> = 797) were used for external validation. Prognostic scores were categorized into low, intermediate-low, intermediate, intermediate-high, and high-risk prognostic groups. The primary outcome was overall survival (OS), with progression-free survival (PFS) secondary.</p>Results:<p>Pretreatment C-reactive protein (CRP) was the most predictive variable for OS. The prognostic tool was optimally defined by CRP, lactate dehydrogenase, derived neutrophil-to-lymphocyte ratio, albumin, PD-L1 expression, performance status, time since metastatic diagnosis, and metastatic site count. Prognostic groups had significantly different OS (<i>c</i>-statistic = 0.72), with median OS ranging from >24 to 3 months for the low- to high-risk groups. Performance was maintained on validation (<i>c</i> = 0.76). These findings were similar for PFS, with median PFS ranging from 5 months to 1 month for the low- to high-risk groups. Benefit of atezolizumab (vs. docetaxel) was greatest in the low-risk group (>3 months median OS improvement), with little benefit apparent for the highest risk group.</p>Conclusions:<p>A prognostic tool was developed and validated to identify patient groups with distinctly different survival following atezolizumab initiation for advanced NSCLC.</p></div>
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