Brooke E Wilson1,2, Bertrand Routy3,4, Adnan Nagrial5,6, Venessa T Chin7,8,9. 1. Kinghorn Cancer Centre, St Vincent's Hospital Sydney, 370 Victoria Street, Darlinghurst, NSW, 2000, Australia. drbrookewilson@icloud.com. 2. St Vincent's Clinical School, University of New South Wales, Darlinghurst, NSW, Australia. drbrookewilson@icloud.com. 3. Hematology-Oncology Division, Department of Medicine, Centre hospitalier de l'Université de Montréal (CHUM), Montréal, QC, Canada. 4. Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada. 5. Westmead Clinical School, University of Sydney, Sydney, NSW, Australia. 6. Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, NSW, Australia. 7. Kinghorn Cancer Centre, St Vincent's Hospital Sydney, 370 Victoria Street, Darlinghurst, NSW, 2000, Australia. 8. St Vincent's Clinical School, University of New South Wales, Darlinghurst, NSW, Australia. 9. Garvan Institute for Medical Research, Darlinghurst, NSW, Australia.
Abstract
PURPOSE: Pre-clinical and early clinical data suggests the microbiome plays an important role in oncogenesis and influences response to immune checkpoint blockade (ICB). The objective of this systematic review and meta-analysis was to determine whether antibiotics affect overall survival (OS) and progression free survival (PFS) in patients with solid malignancies treated with ICB. PATIENTS AND METHODS: A systematic search of EMBASE, MEDLINE and conference proceedings was conducted for observational studies examining the effect of antibiotics on ICB. A random effects study-level meta-analysis was performed with pooling of the hazards ratio (HR) for OS and PFS. Meta-regression was used to determine the impact of the timing of antibiotic exposure on OS. RESULTS: 766 studies were identified, and 18 studies met the inclusion criteria. Of the 2889 patients included, 826 (28.6%) were exposed to antibiotics. The most common malignancies were lung (59%), renal cell carcinoma (RCC) or urothelial carcinoma (16.3%) and melanoma (18.7%). OS was prolonged in those without antibiotic exposure (pooled HR 1.92, 95% CI 1.37-2.68, p < 0.001). The effect of antibiotics on OS was greater in studies defining antibiotic exposure as 42 days prior to initiation of ICB (HR 3.43, 95% CI 2.29-5.14, p < 0.0001). PFS was also longer in patients who did not receive antibiotics (pooled HR 1.65, 95% CI 1.3-2.1, p < 0.0001). CONCLUSION: In patients receiving ICB, OS and PFS are longer in patients who are not exposed to antibiotics. Antibiotic use in the 42 days before starting ICB appears to be most detrimental to outcome.
PURPOSE: Pre-clinical and early clinical data suggests the microbiome plays an important role in oncogenesis and influences response to immune checkpoint blockade (ICB). The objective of this systematic review and meta-analysis was to determine whether antibiotics affect overall survival (OS) and progression free survival (PFS) in patients with solid malignancies treated with ICB. PATIENTS AND METHODS: A systematic search of EMBASE, MEDLINE and conference proceedings was conducted for observational studies examining the effect of antibiotics on ICB. A random effects study-level meta-analysis was performed with pooling of the hazards ratio (HR) for OS and PFS. Meta-regression was used to determine the impact of the timing of antibiotic exposure on OS. RESULTS: 766 studies were identified, and 18 studies met the inclusion criteria. Of the 2889 patients included, 826 (28.6%) were exposed to antibiotics. The most common malignancies were lung (59%), renal cell carcinoma (RCC) or urothelial carcinoma (16.3%) and melanoma (18.7%). OS was prolonged in those without antibiotic exposure (pooled HR 1.92, 95% CI 1.37-2.68, p < 0.001). The effect of antibiotics on OS was greater in studies defining antibiotic exposure as 42 days prior to initiation of ICB (HR 3.43, 95% CI 2.29-5.14, p < 0.0001). PFS was also longer in patients who did not receive antibiotics (pooled HR 1.65, 95% CI 1.3-2.1, p < 0.0001). CONCLUSION: In patients receiving ICB, OS and PFS are longer in patients who are not exposed to antibiotics. Antibiotic use in the 42 days before starting ICB appears to be most detrimental to outcome.
Authors: Roseanna C Wheatley; Elaine Kilgour; Timothy Jacobs; Angela Lamarca; Richard A Hubner; Juan W Valle; Mairéad G McNamara Journal: Br J Cancer Date: 2021-10-18 Impact factor: 9.075
Authors: Daniel Spakowicz; Rebecca Hoyd; Mitchell Muniak; Marium Husain; James S Bassett; Lei Wang; Gabriel Tinoco; Sandip H Patel; Jarred Burkart; Abdul Miah; Mingjia Li; Andrew Johns; Madison Grogan; David P Carbone; Claire F Verschraegen; Kari L Kendra; Gregory A Otterson; Lang Li; Carolyn J Presley; Dwight H Owen Journal: BMC Cancer Date: 2020-05-06 Impact factor: 4.430