Background: The anti-programmed cell death protein-1 (PD-1) inhibitor is one of the second-line
therapies for advanced
hepatocellular carcinoma (HCC) after
sorafenib failure. The goal of this study is to evaluate the feasibility and safety of ablation on the
tumor in patients with advanced HCC who had stable disease or atypical response during single anti-PD-1
therapy after
sorafenib failure. Atypical response defined as mixed responses in different lesions of the same individual (e.g., active or stable lesions mixed with progressive lesions). Patients and Methods: This proof-of-concept clinical trial enrolled 50 patients treated with an anti-PD-1 inhibitor of
nivolumab or
pembrolizumab monotherapy between July 2015 and Nov 2017. Thirty-three cases with stable disease or atypical response to anti-PD-1 inhibitor received subtotal thermal ablation. The safety and the response of ablation during anti-PD-1
therapy were evaluated. The survival was estimated by the Kaplan-Meier curve. Results: Of all 50 patients treated with anti-PD-1
therapy, the rate of response, stable disease, atypical and typical progression were 10% (n = 5), 42% (n = 21) 32% (n = 16), and 12% (n = 6), respectively. Additional ablation improved efficacy with tolerable toxicity, and the response rate was increased from 10 to 24% (12/50). The median time to progression, progression-free survival, and overall survival was 6.1 months (95%CI, 2.6-11.2), 5 months (95%CI, 2.9-7.1), and 16.9 months (95%CI, 7.7-26.1), respectively. Conclusions: This proof-of-concept trial suggested that additional ablation may increase the objective response rate with tolerated toxicity and achieved a relatively better median survival, in advanced HCC patients who had stable or atypical progressive diseases during anti-PD-1
therapy, which may provide a potentially promising strategy to treat advanced HCC. Trial registration number: ClinicalTrials.gov identifier: NCT03939975.