Giulia Galli1, Tiziana Triulzi2, Claudia Proto1, Diego Signorelli1, Martina Imbimbo1, Marta Poggi1, Giovanni Fucà1, Monica Ganzinelli1, Milena Vitali1, Dario Palmieri3, Anna Tessari3, Filippo de Braud4, Marina Chiara Garassino1, Mario Paolo Colombo2, Giuseppe Lo Russo5. 1. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, via G. Venezian 1, 20133, Milan, Italy. 2. Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori, via Amadeo 42, 20133, Milan, Italy. 3. Department of Cancer Biology and Genetics, The Ohio State University, 460w 12(th) avenue, 43210, Columbus, OH, USA. 4. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, via G. Venezian 1, 20133, Milan, Italy; Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, via Festa del Perdono 7, 20122, Milan, Italy. 5. Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, via G. Venezian 1, 20133, Milan, Italy. Electronic address: giuseppe.lorusso@istitutotumori.mi.it.
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.
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 NSCLCpatients treated with IO. MATERIALS AND METHODS: Data about all metastatic NSCLCpatients 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.
Authors: Mara Cruellas; Alfonso Yubero; María Zapata; Eva M Galvez; Marta Gascón; Dolores Isla; Rodrigo Lastra; Luis Martínez-Lostao; Maitane Ocariz; Julián Pardo; Ariel Ramírez; Andrea Sesma; Irene Torres-Ramón; José Ramón Paño Journal: Infect Immun Date: 2021-08-16 Impact factor: 3.441
Authors: David J Pinato; Daria Gramenitskaya; Daniel M Altmann; Rosemary J Boyton; Benjamin H Mullish; Julian R Marchesi; Mark Bower Journal: J Immunother Cancer Date: 2019-11-06 Impact factor: 13.751
Authors: Min Jung Geum; Chungsoo Kim; Ji Eun Kang; Jae Hee Choi; Jae Song Kim; Eun Sun Son; Sun Min Lim; Sandy Jeong Rhie Journal: Pharmaceuticals (Basel) Date: 2021-05-08