Postprogression treatment of lenvatinib plus PD‐1 inhibitor in advanced hepatocellular carcinoma refractory to hepatic arterial infusion chemotherapy

Abstract Purpose This study compares the efficacy and safety of lenvatinib and programmed cell death protein (PD)‐1 versus lenvatinib alone for advanced hepatocellular carcinoma (Ad‐HCC) refractory to hepatic arterial infusion chemotherapy (HAIC). Methods From April 2016 to September 2021, 145 patients with Ad‐HCC refractory to HAIC based on modified Response Evaluation Criteria in Solid Tumors criteria were enrolled by two radiologists and classified into the HAIC‐lenvatinib group (H‐L, n = 87) and HAIC‐lenvatinib‐PD‐1 group (H‐L‐P, n = 58). A propensity score‐matching method was used to reduce selective bias. The overall survival (OS) and postprogression‐free survival (PPS) rates were compared using the Kaplan–Meier method with log‐rank test. Multivariable analyses of independent prognostic factors were evaluated by means of the forward stepwise Cox regression model. Results After propensity score matching 1:1, the median OS was 43.6 months in the H‐L‐P group and was significantly longer than that (18.9 months) of the H‐L group ( p = .009). The median PPS was 35.6 months in the H‐L‐P group and was significantly longer than that (9.4 months) of the H‐L group ( p = .009). Multivariate analyses showed that the factors that ‎significantly affected the OS were‎ α‐fetoprotein (hazard ratio [HR], 2.14; 95% CI, 1.26–3.98; p = .006), early response to HAIC (HR, 0.44; 95% CI, 1.20–3.85; p = .009), and H‐L treatment (HR, ‎0.52; 95% CI, 0.30–0.86; p = .012). Modified albumin‐bilirubin grade (HR, 1.32; 95% CI, 1.03–1.70; p = .026), early response to HAIC (HR, 0.44; 95% CI, 0.25–0.77; p = .004), and H‐L (HR, ‎0.47‎; 95% CI, 0.28–0.78; p = .003) significantly affected the PPS. Conclusions This combination therapy of PD‐1 inhibitors plus lenvatinib has promising survival benefits in the management of patients with Ad‐HCC refractory to HAIC. Plain Language Summary Lenvatinib plus programmed death 1 inhibitor is an effective and safe postprogression treatment and improved significantly overall survival and postprogression‐free survival compared with lenvatinib alone in patients with advanced hepatocellular carcinoma refractory to hepatic arterial infusion chemotherapy.