Antibiotic Therapy is Associated with Worse Outcome in Patients with Hepatocellular Carcinoma Treated with Sorafenib

Abstract

Background: Antibiotic treatment (ABT) affects the outcome of cancer patients treated with immune checkpoint inhibitors (ICIs) and chemotherapy, possibly by altering the gut microbiome. We investigated the impact of ABT on overall survival (OS) and progression-free survival (PFS) in patients with advanced HCC treated with sorafenib.

Methods: HCC patients treated with sorafenib between 05/2006 and 03/2020 at the Medical University of Vienna were retrospectively analyzed. ABT was defined as antibiotic use within 30 days prior to or after sorafenib initiation.

Results: Of 206 patients, the majority was male (n=171, 83%) with a mean age of 66±9.6 years. Half of patients (n=94, 46%) had impaired liver function (Child-Pugh stage B). Median time of follow-up was 10.8 (95% CI: 9.2-12.3) months. ABT was administered in 23 (11%) patients due to different types of proven or clinically suspected bacterial infections (n=17, 74%) and hepatic encephalopathy (n=6, 26%). The median duration of ABT was 14 (IQR: 12-30) days. Penicillin (n=13, 57%), followed by rifaximin (n=6, 26%), fluoroquinolones (n=3, 13%), and cephalosporins (n=1, 4%), was administered in the ABT group. The ABT group had a significantly shorter median OS (4.7 (95% CI: 3.2-6.1) months vs 11.4 (95% CI: 9.9-12.9) months, p=0.012), which was confirmed in multivariable analysis (HR: 1.91 (95% CI: 1.1-3.2), p=0.014). Similarly, PFS trended to be shorter in the ABT group (3.5 (95% CI: 1.6-5.4) months vs 4.8 (95% CI: 3.9-5.7) months, p=0.099). None of the 10 patients with complete or partial response was found in the ABT group.

Conclusion: ABT was independently associated with worse outcomes in sorafenib-treated HCC patients. Prospective studies are needed to elucidate the underlying mechanism.

Keywords: antibiotics; hepatocellular carcinoma; sorafenib; targeted therapy.