| The systemic therapy for advanced hepatocellular carcinoma (HCC) has shifted from molecular target agents to immunotherapy. Globally, six immunotherapies, including atezolizumab + bevacizumab, STRIDE (tremelimumab + durvalumab), atezolizumab + cabozantinib, durvalumab monotherapy, tislelizumab, and pembrolizumab, have shown positive results in clinical trials. In Japan, three immunotherapies, including atezolizumab + bevacizumab, STRIDE, and durvalumab monotherapy, as well as five molecular target agents (sorafenib, lenvatinib, regorafenib, cabozantinib, and ramucirumab), can be used as systemic treatments for unresectable HCC. Following the insurance coverage of STRIDE and durvalumab, the Japanese guidelines for hepatocellular carcinoma treatment were revised. STRIDE is recommended as one of the first-line treatments, and durvalumab is recommended as one of the treatments when combination immunotherapies are not suitable. The treatment algorithm for systemic therapy in the guidelines was also revised. After the approval of atezolizumab + bevacizumab, the first-line systemic therapy shifted from lenvatinib to atezolizumab + bevacizumab, and most of the second-line treatment after atezolizumab + bevacizumab was lenvatinib, based on the results of the HERITAGE study, which analyzed real-world data of systemic therapy for hepatocellular carcinoma in Japan. In real practical settings in Japan, STRIDE is used as the second-line systemic therapy after atezolizumab + bevacizumab. However, the efficacy and safety of STRIDE after atezolizumab + bevacizumab remain unclear. The emergence of these immunotherapies has changed the treatment target to the objective response rate (ORR) because the ORR correlates with overall survival. Several ongoing clinical trials in Japan aim to achieve a higher ORR. One of the treatments is lenvatinib combined with intrahepatic arterial infusion of cisplatin (LEN + CDDP), which has shown an ORR of more than 50%. The ORR of Atezolizumab + bevacizumab and STRIDE is 30% and 20%, respectively. Meanwhile, STRIDE showed a higher rate of progressive disease (PD) although it showed longer durable response. Considering these ORRs and the PD rate, one idea is tailoring systemic treatment based on tumor burden. STRIDE can be selected as the first-line treatment in cases of low tumor burden, and LEN + CDDP can be selected in cases of high tumor burden. Comprehensive genome profiling (CGP) was approved in Japan for second or later treatment selection. We have experienced some cases where treatment was selected based on CGP. |
