Association between antibiotic exposure and survival in patients with hepatocellular carcinoma treated with nivolumab.

e16186 Background: Nivolumab, an immune checkpoint inhibitor, has improved the outcomes of patients with hepatocellular carcinoma (HCC). It is approved for HCC patients previously treated with sorafenib. Outcomes have been reported in previous studies, in malignancies other than HCC, to be worse when patients have been exposed to antibiotics while receiving immune checkpoint inhibitors. We aimed to evaluate the effects of antibiotics on survival in HCC patients treated with nivolumab. Methods: We performed a retrospective review of 59 patients with advanced HCC that have been treated with nivolumab in two academic centers in Saudi Arabia. Patient characteristics, tumor data, antibiotic use (2 weeks prior, during, and 4 weeks after nivolumab therapy), survival data, and other factors were collected. Log-rank test analysis was performed to test the difference in overall survival (OS) time with and without antibiotics use. Results: The majority of patients were males (n=51, 85%), and 38 were Child-Pugh A (64%). A large number of patients had Barcelona Clinic Liver Cancer (BCLC) stage C tumors (n=42, 71%), and 20 patients (34%) used antibiotics. Most patients received nivolumab as second-line therapy after exposure to sorafenib (n=49, 83%). In patients who received nivolumab as first- or second-line therapy (n=57) and did not receive antibiotics, the median OS was double that of patients who received antibiotics (10 vs. 4.5 months, P=0.04). In child A patients who received nivolumab as second-line therapy (n=32), those who were exposed to antibiotics had a statistically significant shorter median OS compared to those who did not (5.5 vs. 20 months, P=0.04). More patients achieved partial response, or complete response (as per modified RECIST criteria) in the cohort that did not receive antibiotics compared to patients who received antibiotics (21% vs. 15%) but that was not statistically significant (P=0.6). Conclusions: This study shows that HCC patients receiving nivolumab have worse survival if they received antibiotics. Antibiotic mediated alteration of the gut microbiome may impact nivolumab response and shorten patient survival. Although this finding may warrant a prospective larger study but it is consistent with other previous studies. Antibiotics should be used very cautiously when treatment with checkpoint inhibitors is considered.