TY - JOUR
T1 - Development and validation of a prognostic model for patients with advanced lung cancer treated with the immune checkpoint inhibitor atezolizumab
AU - Hopkins, Ashley
AU - Kichenadasse, Ganessan
AU - Garrett-Meyer, Elizabeth
AU - Karapetis, Christos
AU - Rowland, Andrew
AU - Sorich, Michael J
PY - 2020/7
Y1 - 2020/7
N2 - PURPOSE: 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. EXPERIMENTAL DESIGN: 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 (n = 751). Data from the single-arm atezolizumab trials BIRCH and FIR (n = 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. RESULTS: 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 (c-statistic = 0.72), with median OS ranging from >24 to 3 months for the low- to high-risk groups. Performance was maintained on validation (c = 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. CONCLUSIONS: A prognostic tool was developed and validated to identify patient groups with distinctly different survival following atezolizumab initiation for advanced NSCLC.
AB - PURPOSE: 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. EXPERIMENTAL DESIGN: 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 (n = 751). Data from the single-arm atezolizumab trials BIRCH and FIR (n = 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. RESULTS: 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 (c-statistic = 0.72), with median OS ranging from >24 to 3 months for the low- to high-risk groups. Performance was maintained on validation (c = 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. CONCLUSIONS: A prognostic tool was developed and validated to identify patient groups with distinctly different survival following atezolizumab initiation for advanced NSCLC.
KW - Immune checkpoint inhibitors (ICI)
KW - non-small cell lung cancer (NSCLC
KW - prognostic model
UR - http://www.scopus.com/inward/record.url?scp=85087469684&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-19-2968
DO - 10.1158/1078-0432.CCR-19-2968
M3 - Article
C2 - 32086341
AN - SCOPUS:85087469684
SN - 1078-0432
VL - 26
SP - 3280
EP - 3286
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 13
ER -