TY - JOUR
T1 - Prognostic Associations of Concomitant Antibiotic Use in Patients with Advanced NSCLC Treated with Atezolizumab
T2 - Sensitivity Analysis of a Pooled Investigation of Five Randomised Control Trials
AU - Manning-Bennett, Arkady T.
AU - Cervesi, Julie
AU - Bandinelli, Pierre Alain
AU - Sorich, Michael J.
AU - Hopkins, Ashley M.
PY - 2023/2
Y1 - 2023/2
N2 - Background: Immune checkpoint inhibitors (ICIs) have been a significant milestone for the treatment of advanced non-small cell lung cancer (NSCLC). However, the efficacy of ICIs can vary substantially between patients, with disparities in treatment outcomes being potentially driving by changes in the microbiome. Antibiotics can cause dysbiosis and are hypothesised to impact the efficacy of ICIs Methods: Data were pooled from five randomised clinical control trials, IMpower130, IMpower131, IMpower150, OAK, and POPLAR, assessing atezolizumab in advanced NSCLC. Cox proportional hazard models were used to determine whether antibiotic use within 6-weeks before and after randomisation was associated with progression-free survival (PFS) and overall survival (OS) outcomes, with data further stratified by programmed death ligand-1 (PD-L1) status. Results: Antibiotic use was significantly associated with worsened PFS (hazard ratio (HR) = 1.19 [1.08–1.30], p ≤ 0.001) and OS (HR = 1.27 [1.13–1.42], p ≤ 0.001) in patients treated with atezolizumab and those not treated with atezolizumab (PFS, HR = 1.21 [1.08–1.36] p < 0.001, OS, HR = 1.33 [1.16–1.51] p < 0.001). These associations were relatively consistent in both PD-L1 positive and PD-L1 negative. Conclusions: Antibiotic use within a ±6-week window was significantly associated with worse PFS and OS.
AB - Background: Immune checkpoint inhibitors (ICIs) have been a significant milestone for the treatment of advanced non-small cell lung cancer (NSCLC). However, the efficacy of ICIs can vary substantially between patients, with disparities in treatment outcomes being potentially driving by changes in the microbiome. Antibiotics can cause dysbiosis and are hypothesised to impact the efficacy of ICIs Methods: Data were pooled from five randomised clinical control trials, IMpower130, IMpower131, IMpower150, OAK, and POPLAR, assessing atezolizumab in advanced NSCLC. Cox proportional hazard models were used to determine whether antibiotic use within 6-weeks before and after randomisation was associated with progression-free survival (PFS) and overall survival (OS) outcomes, with data further stratified by programmed death ligand-1 (PD-L1) status. Results: Antibiotic use was significantly associated with worsened PFS (hazard ratio (HR) = 1.19 [1.08–1.30], p ≤ 0.001) and OS (HR = 1.27 [1.13–1.42], p ≤ 0.001) in patients treated with atezolizumab and those not treated with atezolizumab (PFS, HR = 1.21 [1.08–1.36] p < 0.001, OS, HR = 1.33 [1.16–1.51] p < 0.001). These associations were relatively consistent in both PD-L1 positive and PD-L1 negative. Conclusions: Antibiotic use within a ±6-week window was significantly associated with worse PFS and OS.
KW - antibiotics
KW - atezolizumab
KW - non-small cell lung cancer
UR - http://www.scopus.com/inward/record.url?scp=85148952243&partnerID=8YFLogxK
UR - http://purl.org/au-research/grants/NHMRC/2008119
U2 - 10.3390/biomedicines11020528
DO - 10.3390/biomedicines11020528
M3 - Article
AN - SCOPUS:85148952243
SN - 2227-9059
VL - 11
JO - Biomedicines
JF - Biomedicines
IS - 2
M1 - 528
ER -