Antibiotic use during treatment with immune checkpoint inhibitors (ICI) may improve overall survival for patients with advanced melanoma, a retrospective study at the University of Wisconsin Carbone Cancer Center has found. The findings, published this month, challenge previous assumptions about the negative impact of antibiotics on ICI efficacy and suggest a more nuanced relationship between gut health, antibiotic timing, and cancer treatment outcomes.
The study, which reviewed data from 214 melanoma patients treated between June 2014 and September 2022, divided participants into two groups: 79 who received antibiotic therapy either 30 days before or during ICI treatment, and 135 who did not. Researchers assessed overall survival (OS) and progression-free survival (PFS) as primary outcomes.
While antibiotic use within 30 days before initiating ICI therapy showed a trend toward worse OS outcomes in a univariate analysis, the difference was not statistically significant after adjusting for other factors. While, antibiotic use during ICI therapy correlated with significantly improved OS outcomes, both in univariate (HR, 0.61; P = 0.035) and multivariate analyses (HR, 0.57; P = 0.023). This suggests a potential benefit to antibiotic intervention while patients are undergoing immunotherapy.
The type of antibiotic administered too appeared to play a role. Patients receiving antibiotics without anaerobic coverage demonstrated improved PFS, although this finding also did not reach statistical significance (HR, 0.68; P = 0.092). Forty-two patients received antibiotics with anaerobic coverage, while 37 did not.
The study acknowledged a potential increased risk of immune-related gastritis and/or colitis among patients receiving antibiotics during ICI therapy (odds ratio [OR], 1.892; P = 0.045), particularly when anaerobic coverage was absent. A total of 65 patients developed these conditions during the study period. However, researchers noted the imprecision of these estimates.
The findings contrast with earlier research highlighting the detrimental effects of antibiotics on ICI response. A 2019 study published in Oncoimmunology found that antibiotics were associated with decreased progression-free survival in advanced melanoma patients treated with immune checkpoint inhibitors. More recent research, including a 2024 study published in PubMed, has also indicated that antibiotic exposure prior to ICI can negatively impact both PFS and OS by disrupting the gut microbiome, which is known to influence immune response.
The University of Wisconsin study included patients receiving various ICI regimens, including single-agent pembrolizumab or nivolumab (58.9%), combination nivolumab-ipilimumab (40.6%), and nivolumab with relatlimab. Antibiotics were prescribed for documented infections in 97 cases and for prophylactic purposes in 29, with a small number prescribed for other or unknown reasons.
Researchers emphasized the need for careful antimicrobial stewardship and consideration of antibiotic spectrum and timing in relation to ICI therapy. They called for further investigation into the complex interplay between the gut microbiome, antibiotic use, cancer type, and ICI therapy to better understand its impact on treatment response and survival. The study authors concluded that more research is needed to clarify these relationships.
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