P1.04-16 Early Antibiotic Use Affects the Efficacy of First Line Immunotherapy in Lung Cancer Patients but Route of Administration Seems to be Decisive

Rubio, X. Mielgo; Aguado, Carlos; Sereno, María; Chara, L.E.; Cabezón, L.; Velastegui, A.; López, A.; Castro, R. López; Sotelo, Miguel; Rubio, Judit; Núñez, Juan Antonio Vargas; Fernández, Elia Pérez; Olier, C; Carpeno, J. De Castro; Antoñanzas, Mónica; Falagan, Sandra; Gómez-Barreda, I.; Custódio, Sandra; Cruz, Patricia

doi:10.1016/j.jtho.2019.08.919

Cited by 4 publications

(3 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, the authors did not have sufficient information to perform subgroup analyses by type of antibiotic, duration of use and route of administration. Based on individual studies, these factors could affect the gut microbiome in different ways (Ahmed et al, 2018;Galli et al, 2019;Mielgo Rubio et al, 2019;Tinsley et al, 2020). The above limitations highlight the need for larger, prospective studies and multi-institutional registries that will report antibiotic type, duration and route of administration in order to better clarify this complex relationship.…”

Section: Discussionmentioning

confidence: 99%

“…Seven studies were excluded from the meta-analysis because they provided insufficient information (only median survival in months and not HR, or only qualitative information) to extract data on any of the four outcomes (Dennehy et al, 2018;Greally et al, 2018;Hemadri et al, 2019;Jun et al, 2020;Metges et al, 2018;Resteghini et al, 2019;Riudavets et al, 2019). Forty-one studies were included in the meta-analysis (Abu-Sbeih et al, 2019;Agarwal et al, 2019;Ahmed et al, 2018;Bagley et al, 2019;Barron et al, 2019;Chalabi et al, 2020;Derosa et al, 2018;Do et al, 2018;Elkrief et al, 2019;Facchinetti et al, 2020;Forde et al, 2020;Galli et al, 2019;Guo et al, 2019;Hakozaki et al, 2019;Hogue et al, 2019;Huemer et al, 2019;Iglesias-Santamaria, 2020;Kaderbhai et al, 2017;Kapoor et al, 2020;Kapoor et al, 2019;Khan et al, 2019;Kim et al, 2019;Kulkarni et al, 2019;Lalani et al, 2020;Masini et al, 2019;Mielgo Rubio et al, 2019;Mohiuddin et al, 2021;Ouaknine Krief et al, 2019;Pinato et al, 2019;Rounis et al, 2019;Routy et al, 2018;Schett et al, 2020;…”

Section: Meta-analysismentioning

confidence: 99%

See 1 more Smart Citation

Use of antibiotics is associated with worse clinical outcomes in patients with cancer treated with immune checkpoint inhibitors: A systematic review and meta-analysis

Tsikala‐Vafea

Belani

Vieira

et al. 2021

International Journal of Infectious Diseases

View full text Add to dashboard Cite

Observational and experimental studies suggest that the use of antibiotics close to administration of immune checkpoint inhibitors (ICI) can have a negative effect on tumour response and patient survival, due to microbiome dysbiosis and the resultant suppression of host immune response against neoplastic cells. Methods: A systematic search of PUBMED and EMBASE was undertaken for studies published between 1 January 2017 and 1 June 2020, evaluating the association between the use of antibiotics and clinical outcomes in patients with cancer treated with ICIs. A meta-analysis of the association between the use of antibiotics and clinical outcomes was also performed. Results: Forty-eight studies met the inclusion criteria (12,794 patients). Use of antibiotics was associated with shorter overall survival [hazard ratio (HR) 1.88, 95% confidence interval (CI) 1.59-2.22; adjusted HR 1.87, 95% CI 1.55-2.25] and progression-free survival (HR 1.52, 95% CI 1.36-1.70; adjusted HR 1.93, 95% CI 1.59-2.36), decreased response rate [odds ratio (OR) 0.54, 95% CI 0.34-0.86] and more disease progression (OR 2.00, 95% CI 1.27-3.14). The negative association between the use of antibiotics and progression-free survival was stronger in patients with renal cell carcinoma or melanoma compared with lung cancer. Only antibiotic administration >1 month prior to ICI initiation was associated with increased disease progression. Heterogeneity was substantial for all outcomes. Conclusions: Recent use of antibiotics in patients with cancer treated with ICIs was associated with worse clinical outcomes. Such patients may benefit from dedicated antimicrobial stewardship programmes.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Meta-analysismentioning

confidence: 99%

Use of antibiotics is associated with worse clinical outcomes in patients with cancer treated with immune checkpoint inhibitors: A systematic review and meta-analysis

Tsikala‐Vafea

Belani

Vieira

et al. 2021

International Journal of Infectious Diseases

View full text Add to dashboard Cite

show abstract

“…Individual antibiotics are characterized by a spectrum of antimicrobial activity, and only some antibiotics negatively affect the microbiome in terms of immunotherapy efficacy (21). The route of antibiotic administration may also play a role, with oral administration (predominant in the present cases) being potentially associated with improved efficacy of immunotherapy (47). Moreover, a bias cannot be excluded as patients using antibiotics usually have higher concentrations of CRP, which is a negative predictive and prognostic factor.…”

Section: Discussionmentioning

confidence: 98%

Impact of Concomitant Medication Administered at the Time of Initiation of Nivolumab Therapy on Outcome in Non-small Cell Lung Cancer

Svatoň

Zemanová

et al. 2020

Anticancer Res

View full text Add to dashboard Cite

Aim: To investigate potential association between administration of corticosteroids, antibiotics, probiotics, proton pump inhibitors, non-steroidal anti-inflammatory drugs (NSAID), statins and metformin and outcome in patients with non-small cell lung cancer (NSCLC) treated with nivolumab. Patients and Methods: A total of 224 patients with advanced NSCLC treated at nine comprehensive cancer centers were analyzed in this national retrospective study. Survival statistics were evaluated using Kaplan-Meier method and Cox analysis. Results: Only corticosteroid use had a significant negative effect on the objective response rate. In the univariate analysis, there was no significant effect of the studied concomitant medications on the efficacy of nivolumab. In a subsequent multifactorial analysis, a possible positive effect of the concomitant use of NSAID at the initiation of nivolumab treatment was revealed. Conclusion: The results of the present retrospective exploratory analysis underscore the importance of knowing the exact type of concomitant medication, the route of administration, the dose of medication, and the region of the ongoing study. The present data indicated a significantly higher rate of progression in patients treated with corticosteroids and the possible positive effect of NSAID use at the initiation of nivolumab treatment.Nivolumab is a human monoclonal antibody to programmed cell death protein 1 (PD1) that represents a new therapeutic option in the second-line treatment of advanced non-smallcell lung cancer (NSCLC). Improved efficacy with a more favorable adverse event profile has been documented for nivolumab compared to docetaxel in phase III trials. However, the objective response rate of nivolumab monotherapy is only about 20%, with the disease control rate 2209

show abstract

NSCLC Immunotherapy Efficacy and Antibiotic Use: A Systematic Review and Meta-Analysis

Lurienne

Cervesi

Duhalde

et al. 2020

Journal of Thoracic Oncology

108

View full text Add to dashboard Cite

Immune checkpoint inhibitors (ICIs) have dramatically improved patient outcomes in a variety of tumor types, but with variable efficacy. Recent research has suggested that antibiotic-induced disruption of the microbiota may impact ICI efficacy. We performed a systematic review and metaanalysis of studies that assessed the impact of antibiotic use on the survival of patients diagnosed with NSCLC and treated with ICI. We systematically searched Medline, the Cochrane Library, and major oncology conferences proceedings. Eligible studies mentioned hazard ratio or Kaplan-Meier curves for progression-free survival (PFS) or overall survival (OS) based on antibiotic exposure before or during ICI treatment. We identified 23 eligible studies. The impact of antibiotics was then evaluated in 2208 patients for PFS and 5560 for OS. For both PFS and OS metaanalyses, the between-study heterogeneity was high (Higgins and Thompson I 2 of 69% and 80%, respectively). The pooled hazard ratio was 1.47 (95% confidence interval [CI]: 1.13-1.90) for PFS and 1.69 (95% CI: 1.25-2.29) for OS revealing a significantly reduced survival in patients with NSCLC exposed to antibiotics. The median OS was reduced on average by 6.7 months (95% CI: 5.1-8.4) in the patients exposed to antibiotics. The effect seems to depend on the time window of exposure with stronger effects reported when the patients took antibiotics [À60 days; þ60 days] around ICI initiation. In patients with NSCLC, the findings of the meta-analysis indicate that antibiotic use before or during treatment with ICI leads to a median OS decreased by more than 6 months. Specifically, exposure shortly before or after ICI initiation seems to be particularly detrimental, whereas antibiotic use later during disease course does not seem to alter survival. Because PFS and OS were difficult to compare between studies owing to heterogeneity and the multiple confounding factors identified, further studies are needed to strengthen the understanding of this phenomenon.

show abstract

P1.04-16 Early Antibiotic Use Affects the Efficacy of First Line Immunotherapy in Lung Cancer Patients but Route of Administration Seems to be Decisive

Cited by 4 publications

References 0 publications

Use of antibiotics is associated with worse clinical outcomes in patients with cancer treated with immune checkpoint inhibitors: A systematic review and meta-analysis

Use of antibiotics is associated with worse clinical outcomes in patients with cancer treated with immune checkpoint inhibitors: A systematic review and meta-analysis

Impact of Concomitant Medication Administered at the Time of Initiation of Nivolumab Therapy on Outcome in Non-small Cell Lung Cancer

NSCLC Immunotherapy Efficacy and Antibiotic Use: A Systematic Review and Meta-Analysis

Contact Info

Product

Resources

About