Abstract 1115P
Background
Recent development of immune checkpoint inhibitors (ICI) has revolutionized cancer management. Antibiotics can significantly disrupt the composition of the gut microbiota. This microenvironment plays a key role in the regulation of the immune system. Its modification could affect the efficacy of ICI. We aimed to assess the association between hospital stays with infection and overall survival in patients (pts) treated with ipilimumab.
Methods
All pts treated with ipilimumab between January 2012 and December 2014 were selected from the PMSI national database. Antibiotic exposure was defined as the presence of a hospital stay with an infection during the 2 months prior to the first course of ipilimumab (C1) or within the following month. The primary outcome, overall survival (OS) was defined as the time interval between C1 and date of death; data were censored at the last hospital stay for patients without reported death. OS was estimated by Kaplan-Meier method and compared by the log-rank test and by Cox regression models.
Results
We studied 44357 hospital stays from 97 centres, involving 1661 pts (1072 in 2014). Our data appear to be complete: French National Cancer Institute (INCA) lists 1080 pts in 2014. All pts received ipilimumab as monotherapy for an advanced melanoma. Overall, 123 of the 1661 (7.4%) pts were considered as receiving antibiotics in hospital during the exposure defined period. The most frequent sites of infection were: skin (21.6%), respiratory tract (20.4%) and digestive system (14.4%). Infection was associated with a shorter OS: median 6.3 versus 15.4 months, hazard ratio, HR=1.91; 95% confidence interval (CI) 1.48-2.46, p=10-6. In multivariate analysis adjusted for covariates, the association between infection and OS remained significant: HR=1.71; 95%CI, 1.32-2.21, p=10-5; malnutrition and brain metastases were also significantly associated with poor OS: HR=4.37; p=10-13; and HR=1.90; p=10-11, respectively.
Conclusions
Infection and antibiotic administration in hospital around the first course of ipilimumab appear to be associated with a significant reduction in clinical benefit from ipilimumab in advanced melanoma.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
N. Penel: Honoraria (institution), Research grant/Funding (institution): Bayer; Honoraria (institution), Research grant/Funding (institution): PharmaMar; Honoraria (institution): Pfizer; Honoraria (institution): Astellas; Honoraria (institution): AstraZeneca; Honoraria (institution): Ipsen. All other authors have declared no conflicts of interest.