ESMO 2021: Antibiotic Therapy and Outcome from Nivolumab in Metastatic Renal Cell Carcinoma (mRCC) Patients: Results of the GETUG-AFU 26 NIVOREN Multicentric Phase II Study

( The NIVOREN GETUF AFU 26 study is a French multi-center prospective study to evaluate the safety and efficacy of the anti-PD-1 checkpoint agent nivolumab in a “real world” setting after failure of 1-2 tyrosine kinase inhibitor in metastatic renal cell carcinoma (mRCC). As antibiotic use around the time of starting immune checkpoint blockade has been associated with reduced efficacy in multiple cancer types, Dr. Derosa and colleagues identified patients from the NIVOREN study who received antibiotics between 60 days prior to starting therapy to 42 days after starting nivolumab and assessed the impact on clinical outcomes and toxicities.

A total of 104 patients were identified from the 707 patients examined who received antibiotics within the designated time window. The clinical characteristics of these patients are shown below.


The administration of antibiotics was associated with a numerically decreased objective response rate and a numerically higher incidence of progressive disease. This difference was not statistically significant. The median progression-free survival in antibiotic recipients was 2.6 months versus 3.8 months in patients who did not receive antibiotics (hazard ratio for progression with antibiotic use 1.24 (0.99-1.55), p = 0.0564).


Notably, the median overall survival in patients that did not receive antibiotics around the time of nivolumab was 25 months compared to 13 months for patients who did receive antibiotics. This difference was statistically significant, as shown below.


A multivariate Cox regression analysis was used to assess the impact of antibiotic use on overall survival after correcting for other prognostic factors. After adjusting for the parameters listed below, antibiotic use remained statistically significantly associated with worsened overall survival.


The data presented suggest (1) that antibiotic use around the time of nivolumab initiation is frequent, with almost 15% of patients in this study receiving antibiotics 60 days before through 42 days after starting nivolumab, and (2) antibiotic use during this time frame appears to compromise overall survival in these patients. Prospective analyses may help understand whether antibiotic use is a surrogate for a more frail/immunodeficient population, or whether antibiotics directly impair the immune response to mRCC.

Presented by: Lisa Derosa, MD, PhD, Medical Oncology Department, Institut Gustave Roussy, Paris, France

Written by: Alok Tewari, MD, PhD – Genitourinary Medical Oncologist, Instructor in Medicine, Dana-Farber Cancer Institute, Harvard Medical School,
Twitter: @aloktewar during the 2021 European Society for Medical Oncology (ESMO) Annual Congress 2021, Thursday, Sep 16, 2021 – Tuesday, Sep 21, 2021.


  1. Lisa Derosa, Bertrand Routy, Antoine Desilets, Romain Daillère, Safae Terrisse, Guido Kroemer and Laurence Zitvogel. Microbiota-Centered Interventions: The Next Breakthrough in Immuno-Oncology? Cancer Discov August 16 2021. DOI: 10.1158/2159-8290.CD-21-0236