Safety of nivolumab in combination with prior or concurrent radiation therapy in hepatocellular carcinoma

Nivolumab has been demonstrated to be effective for the treatment of unresectable hepatocellular carcinoma (HCC). While many patients may additionally benefit from radiation therapy (RT), the toxicity of combination nivolumab and RT is unknown. Patients who underwent liver-directed RT prior to or concurrent with nivolumab for HCC at our institution were reviewed. Toxicity was assessed by Common Terminology Criteria for Adverse Effects v5.0 criteria until disease progression, change in systemic therapy, additional liver-targeted locoregional therapy (LRT), or death. Prevalence ratios (PR) were compared for patients undergoing prior and concurrent RT. Childs-Turcotte-Pugh (CTP) and Albumin-Bilirubin (ALBI) scores at 1-, 3-, and 6-months were compared with baseline. We identified 55 patients with median follow-up 6.0 months; 34 (62%) received prior and 21 (38%) received concurrent RT. Grade 3+ toxicity occurred in 8 patients (17%). Grade 3+ toxicities did not differ between prior and concurrent RT cohorts on the univariable analysis (PR 1.91; 95% CI 0.42, 8.59) but were higher in the prior RT cohort on the multivariable analysis (PR 5.42; 95% CI 1.42, 20.67; p = 0.013). Mean CTP scores increased from baseline (6.33) at 1 month (7.04; 95% CI 6.80, 7.27) and 3 months (6.81; 95% CI 6.43, 7.19) and thereafter normalized; mean ALBI scores increased from baseline (− 1.93) at 1 month (− 1.75; 95% CI − 1.84, − 1.66) with no difference thereafter. Combination RT and nivolumab is generally safe in the management of unresectable HCC with a low rate of serious adverse events. Prospective trials investigating the efficacy of combination nivolumab and RT are warranted.