Association between antibiotic-immunotherapy exposure ratio and outcome in metastatic non small cell lung cancer

Giulia Galli, Tiziana Triulzi, Claudia Proto, Diego Signorelli, Martina Imbimbo, Marta Poggi, Giovanni Fucà, Monica Ganzinelli, Milena Vitali, Dario Palmieri, Anna Tessari, Filippo de Braud, Marina Chiara Garassino, Mario Paolo Colombo, Giuseppe Lo Russo

Research output: Contribution to journalArticle

Abstract

Objectives: Immunotherapy (IO) is effective in metastatic Non Small Cell Lung Cancer (NSCLC). Gut microbiota has an impact on immunity and its imbalance due to antibiotics may impair the efficacy of IO. We investigated this topic in a case series of NSCLC patients treated with IO. Materials and Methods: Data about all metastatic NSCLC patients treated with IO between 04/2013 and 01/2018 were collected. Patients were stratified according to antibiotic use during the Early IO Period (EIOP), and according to the Antibiotic-Immunotherapy Exposure Ratio (AIER) defined as “days of antibiotic/days of IO” during the Whole IO Period (WIOP). Survival was estimated using the Kaplan-Meier method. Log-rank test was used to compare the curves. Multivariate analyses were performed with the Cox model. Results: We analyzed 157 patients. Forty-six patients received antibiotics during the WIOP, 27 patients during the EIOP. No differences in either Progression-Free Survival (PFS) or Overall Survival (OS) were observed according to antibiotic use during the EIOP (p = 0.1772 and p = 0.2492, respectively). Considering the WIOP, median AIER was 4.2%. The patients with a higher AIER had worse PFS (p < 0.0001) and OS (p = 0.0004) than the others. Results were significant also after correction for the IO line (p = 0.0018 for PFS) and performance status (p < 0.0001 for PFS, p = 0.0052 for OS). Conclusion: Although no difference in outcome were observed with antibiotic use in the EIOP, a detrimental effect became evident for patients with a higher AIER in the WIOP. If its relevance is confirmed, AIER may become an innovative variable for estimating the impact of antibiotics on IO efficacy.

Original languageEnglish
Pages (from-to)72-78
Number of pages7
JournalLung Cancer
Volume132
DOIs
Publication statusPublished - Jun 2019

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Non-Small Cell Lung Carcinoma
Immunotherapy
Anti-Bacterial Agents
Disease-Free Survival
Survival
Proportional Hazards Models
Immunity
Multivariate Analysis

Keywords

  • Antibiotic
  • Immunotherapy
  • Microbiota
  • Non small cell lung cancer

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Association between antibiotic-immunotherapy exposure ratio and outcome in metastatic non small cell lung cancer. / Galli, Giulia; Triulzi, Tiziana; Proto, Claudia; Signorelli, Diego; Imbimbo, Martina; Poggi, Marta; Fucà, Giovanni; Ganzinelli, Monica; Vitali, Milena; Palmieri, Dario; Tessari, Anna; de Braud, Filippo; Garassino, Marina Chiara; Colombo, Mario Paolo; Lo Russo, Giuseppe.

In: Lung Cancer, Vol. 132, 06.2019, p. 72-78.

Research output: Contribution to journalArticle

Galli, G, Triulzi, T, Proto, C, Signorelli, D, Imbimbo, M, Poggi, M, Fucà, G, Ganzinelli, M, Vitali, M, Palmieri, D, Tessari, A, de Braud, F, Garassino, MC, Colombo, MP & Lo Russo, G 2019, 'Association between antibiotic-immunotherapy exposure ratio and outcome in metastatic non small cell lung cancer', Lung Cancer, vol. 132, pp. 72-78. https://doi.org/10.1016/j.lungcan.2019.04.008
Galli, Giulia ; Triulzi, Tiziana ; Proto, Claudia ; Signorelli, Diego ; Imbimbo, Martina ; Poggi, Marta ; Fucà, Giovanni ; Ganzinelli, Monica ; Vitali, Milena ; Palmieri, Dario ; Tessari, Anna ; de Braud, Filippo ; Garassino, Marina Chiara ; Colombo, Mario Paolo ; Lo Russo, Giuseppe. / Association between antibiotic-immunotherapy exposure ratio and outcome in metastatic non small cell lung cancer. In: Lung Cancer. 2019 ; Vol. 132. pp. 72-78.
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abstract = "Objectives: Immunotherapy (IO) is effective in metastatic Non Small Cell Lung Cancer (NSCLC). Gut microbiota has an impact on immunity and its imbalance due to antibiotics may impair the efficacy of IO. We investigated this topic in a case series of NSCLC patients treated with IO. Materials and Methods: Data about all metastatic NSCLC patients treated with IO between 04/2013 and 01/2018 were collected. Patients were stratified according to antibiotic use during the Early IO Period (EIOP), and according to the Antibiotic-Immunotherapy Exposure Ratio (AIER) defined as “days of antibiotic/days of IO” during the Whole IO Period (WIOP). Survival was estimated using the Kaplan-Meier method. Log-rank test was used to compare the curves. Multivariate analyses were performed with the Cox model. Results: We analyzed 157 patients. Forty-six patients received antibiotics during the WIOP, 27 patients during the EIOP. No differences in either Progression-Free Survival (PFS) or Overall Survival (OS) were observed according to antibiotic use during the EIOP (p = 0.1772 and p = 0.2492, respectively). Considering the WIOP, median AIER was 4.2{\%}. The patients with a higher AIER had worse PFS (p < 0.0001) and OS (p = 0.0004) than the others. Results were significant also after correction for the IO line (p = 0.0018 for PFS) and performance status (p < 0.0001 for PFS, p = 0.0052 for OS). Conclusion: Although no difference in outcome were observed with antibiotic use in the EIOP, a detrimental effect became evident for patients with a higher AIER in the WIOP. If its relevance is confirmed, AIER may become an innovative variable for estimating the impact of antibiotics on IO efficacy.",
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T1 - Association between antibiotic-immunotherapy exposure ratio and outcome in metastatic non small cell lung cancer

AU - Galli, Giulia

AU - Triulzi, Tiziana

AU - Proto, Claudia

AU - Signorelli, Diego

AU - Imbimbo, Martina

AU - Poggi, Marta

AU - Fucà, Giovanni

AU - Ganzinelli, Monica

AU - Vitali, Milena

AU - Palmieri, Dario

AU - Tessari, Anna

AU - de Braud, Filippo

AU - Garassino, Marina Chiara

AU - Colombo, Mario Paolo

AU - Lo Russo, Giuseppe

PY - 2019/6

Y1 - 2019/6

N2 - Objectives: Immunotherapy (IO) is effective in metastatic Non Small Cell Lung Cancer (NSCLC). Gut microbiota has an impact on immunity and its imbalance due to antibiotics may impair the efficacy of IO. We investigated this topic in a case series of NSCLC patients treated with IO. Materials and Methods: Data about all metastatic NSCLC patients treated with IO between 04/2013 and 01/2018 were collected. Patients were stratified according to antibiotic use during the Early IO Period (EIOP), and according to the Antibiotic-Immunotherapy Exposure Ratio (AIER) defined as “days of antibiotic/days of IO” during the Whole IO Period (WIOP). Survival was estimated using the Kaplan-Meier method. Log-rank test was used to compare the curves. Multivariate analyses were performed with the Cox model. Results: We analyzed 157 patients. Forty-six patients received antibiotics during the WIOP, 27 patients during the EIOP. No differences in either Progression-Free Survival (PFS) or Overall Survival (OS) were observed according to antibiotic use during the EIOP (p = 0.1772 and p = 0.2492, respectively). Considering the WIOP, median AIER was 4.2%. The patients with a higher AIER had worse PFS (p < 0.0001) and OS (p = 0.0004) than the others. Results were significant also after correction for the IO line (p = 0.0018 for PFS) and performance status (p < 0.0001 for PFS, p = 0.0052 for OS). Conclusion: Although no difference in outcome were observed with antibiotic use in the EIOP, a detrimental effect became evident for patients with a higher AIER in the WIOP. If its relevance is confirmed, AIER may become an innovative variable for estimating the impact of antibiotics on IO efficacy.

AB - Objectives: Immunotherapy (IO) is effective in metastatic Non Small Cell Lung Cancer (NSCLC). Gut microbiota has an impact on immunity and its imbalance due to antibiotics may impair the efficacy of IO. We investigated this topic in a case series of NSCLC patients treated with IO. Materials and Methods: Data about all metastatic NSCLC patients treated with IO between 04/2013 and 01/2018 were collected. Patients were stratified according to antibiotic use during the Early IO Period (EIOP), and according to the Antibiotic-Immunotherapy Exposure Ratio (AIER) defined as “days of antibiotic/days of IO” during the Whole IO Period (WIOP). Survival was estimated using the Kaplan-Meier method. Log-rank test was used to compare the curves. Multivariate analyses were performed with the Cox model. Results: We analyzed 157 patients. Forty-six patients received antibiotics during the WIOP, 27 patients during the EIOP. No differences in either Progression-Free Survival (PFS) or Overall Survival (OS) were observed according to antibiotic use during the EIOP (p = 0.1772 and p = 0.2492, respectively). Considering the WIOP, median AIER was 4.2%. The patients with a higher AIER had worse PFS (p < 0.0001) and OS (p = 0.0004) than the others. Results were significant also after correction for the IO line (p = 0.0018 for PFS) and performance status (p < 0.0001 for PFS, p = 0.0052 for OS). Conclusion: Although no difference in outcome were observed with antibiotic use in the EIOP, a detrimental effect became evident for patients with a higher AIER in the WIOP. If its relevance is confirmed, AIER may become an innovative variable for estimating the impact of antibiotics on IO efficacy.

KW - Antibiotic

KW - Immunotherapy

KW - Microbiota

KW - Non small cell lung cancer

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