Antibiotic Use Does Not Appear to Influence Response to Nivolumab

Kaderbhai, C.; Richard, Corentin; Fumet, Jean David; Aarnink, Anne; Foucher, Pascal; Coudert, Bruno; Favier, Laure; Lagrange, Aurélie; Limagne, Emeric; Boidot, Romain; Ghiringhelli, François

doi:10.21873/anticanres.11680

Cited by 59 publications

(53 citation statements)

References 19 publications

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“…26 In addition, Kaderbhai et al found that ATB use 3 months before nivolumab immunotherapy did not affect the clinical efficacy of ICI. 29 It should be noted that the favorable results of ATB use 60 days prior to therapy could also be due to recall bias over the unavailability of ATB treatment data in retrospective studies. Thus, future large-scale, prospective studies are required to investigate the impact of the use time, duration, route, and drug type of ATBs on the clinical efficacy of ICI immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, 19 studies were included in our quantitative analysis ( Figure 1). 10,[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] A total of 2,740 patients [mean: 144; median with range: 109 (30-360)] were included in our analysis. The included studies were published between 2017 and 2019 (17/19 studies, 89%, were published in 2018 and 2019) from the United States, the United Kingdom, China, Japan, Canada, Switzerland, Greece, Korea, Austria, and France.…”

Section: Study Selection and Associated Characteristicsmentioning

confidence: 99%

“…With regards to the time of ATB use, 11 studies provided results on the association between pre-therapy ATB use and ICI efficacy, 13,[15][16][17][18][19]21,23,24,26,28 nine studies provided data on the association between pre-therapy or posttherapy ATB use and ICI efficacy, 10,12,14,20,22,24,25,27,29 and only one study provided results on the association between posttherapy ATB use and ICI efficacy. 24 A total of 14 studies used anti-PD-1/PD-L1 inhibitors, 10,12,13,15,16,18,20,[22][23][24][25][27][28][29] three studies used anti-PD-1/PD-L1 inhibitors and/or anti-CTLA-4 inhibitors, 17,21,26 and two studies did not report the type of ICI drug. 14,19 Of the eligible studies, eight studies were complete cohort studies 10,12,16,17,24,26,…”

Section: Study Selection and Associated Characteristicsmentioning

confidence: 99%

“…24 A total of 14 studies used anti-PD-1/PD-L1 inhibitors, 10,12,13,15,16,18,20,[22][23][24][25][27][28][29] three studies used anti-PD-1/PD-L1 inhibitors and/or anti-CTLA-4 inhibitors, 17,21,26 and two studies did not report the type of ICI drug. 14,19 Of the eligible studies, eight studies were complete cohort studies 10,12,16,17,24,26,27,29 and 11 studies provided only an abstract. [13][14][15][18][19][20][21][22][23]25,28 The main characteristics of the included studies are listed in Table 1.…”

Section: Study Selection and Associated Characteristicsmentioning

confidence: 99%

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Antibiotic use and the efficacy of immune checkpoint inhibitors in cancer patients: a pooled analysis of 2740 cancer patients

et al. 2019

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The gut microbiota plays a critical role in the anti-tumor immune response. There is increasing data showing that antibiotics (ATBs) change the composition of the gut microbiota and affect the efficacy of immune checkpoint inhibitors (ICIs). However, this is the first meta-analysis to evaluate the association between ATB use and ICI efficacy in cancer patients to provide a better understanding of the strength of this association. We performed a literature search for relevant studies that evaluated the relationship between ATB use and ICI efficacy using the PubMed, Embase, and conference databases. The primary outcomes consisted of overall survival (OS) and progression-free survival (PFS) measured by hazard ratios (HR) and corresponding 95% confidence intervals (CI). Subgroup and sensitivity analyses were also performed. A total of 19 eligible studies comprising 2,740 cancer patients treated with ICIs were included in the analysis. Our results indicated that ATB use was negatively associated with OS in cancer patients (HR = 2.37; 95% CI = 2.05–2.75; P < .001), without heterogeneity (I2 = 0.0%; P = .851). Moreover, ATB use significantly reduced PFS in patients treated with ICIs (HR = 1.84; 95% CI = 1.49–2.26; P < .001; I2 = 56.2%). Similar results were obtained in the subgroup analyses stratified by the time of ATB use and cancer type. Sensitivity analyses confirmed the stability of our results. Therefore, the findings of our meta-analysis indicated that ATB use is negatively associated with OS and PFS in cancer patients treated with ICI immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Section: Study Selection and Associated Characteristicsmentioning

confidence: 99%

Section: Study Selection and Associated Characteristicsmentioning

confidence: 99%

Section: Study Selection and Associated Characteristicsmentioning

confidence: 99%

See 2 more Smart Citations

Antibiotic use and the efficacy of immune checkpoint inhibitors in cancer patients: a pooled analysis of 2740 cancer patients

et al. 2019

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“…This, in turn, induces the expression of immune checkpoint molecules, including PD-L1 on various cells. Therefore, in patients after acute infection and antibiotic therapy, the effect of immunotherapy may be negligible [12].…”

Section: Review Of the Literaturementioning

confidence: 99%

The impact of intestinal microflora on the effectiveness of immunotherapy with antibodies against immune checkpoints — case report and literature review

et al. 2018

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Inhibitors of immune checkpoints (anti-PD-1 or anti-PD-L1 monoclonal antibodies) are effective in non-small cell lung cancer treatment, significantly extending the overall survival of some patients. However, there are no predictive factors, which could allow precise qualification of cancer patients to immunotherapy. The best evaluated in this regard is the expression of PD-L1 molecule on tumour cells, the occurrence of which is associated with higher response rate and prolonged time to progression in patients undergoing immunotherapy. Some recent reports indicate that the composition of the patient's intestinal microflora, the presence of inflammation, and antibiotic therapy used before or during immunotherapy may affect the effectiveness of anti-PD-1 or anti-PD-L1 antibodies. Disturbance of the body's natural balance, e.g. due to the use of antibiotics, may reduce the effectiveness of immunotherapy. This may be due to a lack of stimulation of the immune system by antigens from bacteria found naturally in the gut. On the other hand, supplementing the microflora with the necessary ingredients can improve the effectiveness of immunotherapy. The future goal is to develop so-called "immunotherapeutic probiotics", the use of which could enhance the effect of cancer immunotherapy.

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The impact of antibiotic selection and interval time among advanced non‐small cell lung cancer patients receiving prior antibacterial treatment and first‐line chemotherapy

Tian

Mei

et al. 2022

Cancer Medicine

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Background To determine whether antibiotic use before chemotherapy is associated with chemotherapy responses and patient outcomes among NSCLC patients and define the optimal interval between chemotherapy initiation and antibiotic treatment. Materials and methods One thousand four hundred and four advanced NSCLC patients receiving first‐line platinum‐based doublets therapy were retrospectively analyzed. Kaplan–Meier curve evaluated the impact of antibiotic use and type of antibiotics on the survival of patients. The factors affect the patient's prognosis were further confirmed by Cox regression. The optimal interval between antibiotic treatment and the initiation of chemotherapy was determined by the X‐tile program. Results NSCLC patients of 33.5% advanced underwent broad‐spectrum antibiotic treatment prior to chemotherapy. In the chemotherapy only (Chemo) and chemotherapy plus antiangiogenesis (Chemo‐angio) treatment groups, prior antibiotic treatment was associated with worse OS (Chemo: 13.8 vs. 17.6 months, p < 0.001; Chemo‐angio:11.9 vs. 18.1 months, p = 0.012) and PFS (Chemo: 3.7 vs. 5.8 months, p < 0.001; Chemo‐angio: 3.1 vs. 5.9 months, p < 0.001). Cox regression analysis revealed prior antibiotic administration as an independent predictor of OS and PFS (HR for PFS/OS: 1.925/1.452, both p < 0.001). Antibiotic usage duration (HR for PFS/OS: 1.030/1.036, p = 0.009/0.001) and type (PFS/OS: p < 0.001/p = 0.01) also showed significant association with patient prognosis, with calculated interval time cutoff values of 2, 4, and 2 days for fluoroquinolones, β‐lactamase inhibitors, and cephalosporins, respectively. Conclusion Antibiotic use before first‐line chemotherapy was associated with poor results in advanced NSCLC patients; treatment length and type being strongly correlated with patient outcomes. Appropriate prolongation of the time between two treatments may enhance patient survival. Further prospective research is however necessary.

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Antibiotic Use Does Not Appear to Influence Response to Nivolumab

Abstract: Microbiota modification induced by antibiotics does not appear to affect the efficacy of nivolumab in patients with NSCLC.

Cited by 59 publications

References 19 publications

Antibiotic use and the efficacy of immune checkpoint inhibitors in cancer patients: a pooled analysis of 2740 cancer patients

Antibiotic use and the efficacy of immune checkpoint inhibitors in cancer patients: a pooled analysis of 2740 cancer patients

The impact of intestinal microflora on the effectiveness of immunotherapy with antibodies against immune checkpoints — case report and literature review

The impact of antibiotic selection and interval time among advanced non‐small cell lung cancer patients receiving prior antibacterial treatment and first‐line chemotherapy

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