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Gut dysbiosis may reduce the efficacy of immune checkpoint inhibitors (ICIs)
.
Antibiotics and proton pump inhibitors (PPIs) are commonly used drugs that cause intestinal disorders
Gut dysbiosis may reduce the efficacy of immune checkpoint inhibitors (ICIs)
This study pooled 5 RCTs (IMpower130, IMpower131, IMpower150, OAK and POPLAR)
evaluating atezolizumab in advanced NSCLC .
Subgroups based on antibiotic and PPI use at randomization were evaluated for the effect of atezolizumab on efficacy (hazard ratio with 95% confidence interval) .
The relationship between antibiotic and PPI use and pretreatment peripheral blood immunophenotype was also explored .
This study pooled 5 RCTs (IMpower130, IMpower131, IMpower150, OAK and POPLAR)
Of the 4458 patients pooled , 2723 patients were treated with atezolizumab and 1735 patients were not treated with atezolizumab .
Of the patients treated with atezolizumab , 194 (7%) received antibiotics within the first 30 days of treatment, and 762 (28%) were recorded using a PPI at the start of treatment .
Of the atezolizumab -naïve patients , 91 (5%) received antibiotics within the first 30 days of treatment and 463 (27%) were on PPIs .
The median follow-up time (95% CI) was 19 months (18-19 months ) .
Of the 4458 patients pooled , 2723 2723 patients were treated with atezolizumab,1735 1735 patients were not treated with atezolizumab
Among patients treated with atezolizumab, antibiotic use was associated with OS (univariate analysis, HR [95% CI], 1.
When further analyzing the efficacy of antibiotic use on atezolizumab, the HR (95% CI) for OS with atezolizumab was 0.
73 (0.
53–0.
99) for antibiotic users and 0.
82 (0.
74–0.
91) for those without antibiotics (p[interaction]=0.
35) ), suggesting that antibiotic use did not affect the efficacy of atezolizumab
.
73 (0.
53–0.
99) for antibiotic users and 0.
82 (0.
74–0.
91) for those without antibiotics (p[interaction]=0.
35) ), suggesting that antibiotic use did not affect the efficacy of atezolizumab
.
When further analyzing the efficacy of antibiotic use on atezolizumab, the HR (95% CI) for OS with atezolizumab was 0.
OS in patients treated with atezolizumab, PPI use (univariate analysis, HR [95% CI], 1.
30 [1.
17–1.
46], p < 0.
001; or adjusted 1.
23 [1.
09–1.
37], p < 0.
001), and PFS (univariate analysis, HR [95% CI], 1.
18 [1.
07–1.
29], p < 0.
001; or adjusted 1.
15 [1.
03–1.
28], p=0.
01) was worse
.
In atezolizumab-naïve patients, antibiotic use had no effect on OS (HR [95% CI], 1.
OS in patients treated with atezolizumab, PPI use (univariate analysis, HR [95% CI], 1.
When further analyzing the efficacy of PPI use on atezolizumab, the HR (95% CI) for OS with atezolizumab was 1.
00 (0.
85–1.
17) for PPI users and 0.
76 (0.
69–0.
83) for those without PPIs (p[interaction]=0.
003) ), suggesting that PPI use is associated with reduced efficacy of atezolizumab
.
00 (0.
85–1.
17) for PPI users and 0.
76 (0.
69–0.
83) for those without PPIs (p[interaction]=0.
003) ), suggesting that PPI use is associated with reduced efficacy of atezolizumab
.
When further analyzing the efficacy of PPI use on atezolizumab, the HR (95% CI) for OS with atezolizumab was 1.
PPI use was associated with an 18% and 9% reduction in CD19+ and CD16+CD56+ peripheral blood immune cell counts, respectively (p<0.
01); PPI use was also associated with a 9% reduction in lymphocyte counts (p<0.
01)
.
With antibiotic use, no significant changes in immune cell counts were observed
PPI use was associated with an 18% and 9% reduction in CD19+ and CD16+CD56+ peripheral blood immune cell counts, respectively (p<0.
01); PPI use was also associated with a 9% reduction in lymphocyte counts (p<0.
01)
.
With antibiotic use, no significant changes in immune cell counts were observed
.
PPI use was associated with an 18% and 9% reduction in CD19+ and CD16+CD56+ peripheral blood immune cell counts, respectively (p<0.
01); PPI use was also associated with a 9% reduction in lymphocyte counts (p<0.
01)
.
With antibiotic use, no significant changes in immune cell counts were observed
.
In conclusion, the study showed that antibiotics did not significantly affect the efficacy of atezolizumab in patients with advanced NSCLC , but the use of PPIs could reduce the efficacy .
In conclusion, the study showed that antibiotics did not significantly affect the efficacy of atezolizumab inpatients with advanced NSCLC , but the use of PPIs could reduce the efficacy .
In conclusion, the study showed that the use of advanced NSCLC patients showed that antibiotics did not significantly affect the efficacy of atezolizumab in patients with advanced NSCLC, but the use of PPIs could reduce its efficacy .
Antibiotics did not significantly affect the efficacy of atezolizumab, but the use of PPIs reduced its efficacy .
Original source:
Original source:Hopkins AM, Badaoui S, Kichenadasse G, Karapetis CS, McKinnon RA, Rowland A, Sorich MJ.
Efficacy of Atezolizumab in Patients With Advanced NSCLC Receiving Concomitant Antibiotic or Proton Pump Inhibitor Treatment: Pooled Analysis of Five Randomized Control Trials.
J Thorac Oncol.
2022 Feb 17: S1556-0864(22)00093-4.
doi: 10.
1016/j.
jtho.
2022.
02.
003.
Epub ahead of print.
PMID: 35183773.
Efficacy of Atezolizumab in Patients With Advanced NSCLC Receiving Concomitant Antibiotic or Proton Pump Inhibitor Treatment: Pooled Analysis of Five Randomized Control Trials.
J Thorac Oncol.
2022 Feb 17: S1556-0864(22)00093-4.
doi: 10.
1016/j.
jtho.
2022.
02.
003.
Epub ahead of print.
PMID: 35183773.
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