- Email: [email protected]
Hepatic arterial infusion chemotherapy for hepatocellular carcinoma: currnet status and future perspective
Annals of Oncology 30 (Supplement 6): vi53, 2019 doi:10.1093/annonc/mdz351
WORKSHOP 1 : HOW DO WE PROPERLY USE VARIOUS REGIMENS IN CHEMOTHERAPY FOR ADVANCED HCC? WS1
1
Hepatic arterial infusion chemotherapy for hepatocellular carcinoma: currnet status and future perspective
Hepatic arterial infusion chemotherapy (HAIC) is a treatment modality that provides direct delivery of highly concentrated anticancer drugs into tumour-feeding vessels using an intraarterial catheter technique and decreases the systemic distribution through the first-pass effect of the liver. Therefore, HAIC is expected to have strong anticancer effects and mild toxicity, and it has been used mainly for advanced hepatocellular carcinoma (HCC) with macrovascular invasion. Several studies have demonstrated the efficacy and safety of HAIC even after sorafenib (SOR) became a standard treatment for advanced HCC following the result of a phase III study: however, the results were not consistent with each other because of different patients and different treatment regimens. Moreover, no phase III trial was conducted to detect the efficacy of HAIC compared to that of SOR. Based on the results, HAIC could not become a standard treatment for patients with advanced HCC. As a perspective of HAIC, combination treatment containing tyrosine kinase inhibitors (TKIs) such as SOR or lenvatinib (LEN) may be an area to develop. Although LEN has shown non-inferiority to sorafenib in terms of survival, both SOR and LEN have several toxicities. Therefore, SOR and LEN are difficult to combine with other treatments, whereas HAIC could be a candidate because of its mild toxicity. Two prospective randomised trials that evaluated the efficacy of SOR and HAIC combination therapy showed promising results, and a phase III study that tests the efficacy of TKIs and HAIC combination therapy is warranted. Another aspect regarding HAIC to develop may be the treatment for patients with Child-Pugh class B/C disease. Several new chemotherapeutic agents have been developed; however, these treatments, including SOR and LEN, are only intended for patients with Child-Pugh class A disease. HAIC could be developed for such unmet medical needs.
5
Recent advances in systemic therapy for hepatocellular carcinoma
Masafumi Ikeda Department of Hepatobiliary & Pancreatic Oncology, National Cancer Center Hospital East For the treatment of advanced hepatocellular carcinoma (HCC), phase III trials have shown that sorafenib and lenvatinib as first-line treatment agents, and regorafenib, ramcirumab, and cabozantinib as subsequent-line treatment agents in combination with sorafenib, offer survival benefit. At present, sorafenib and lenvatinib for patients with advanced HCC, and regorafenib for patients who are refractory to systemic therapy are reimbursed and can be available in Japan. In the near future, ramucirumab is also expected to be approved for further treatment after second-line treatment of HCC patients with serum AFP levels of 400 ng/mL or more, and data on cabozantinib are also expected to be submitted for approval. Furthermore, the efficacy of immune checkpoint inhibitors is also expected. In regard to the anti-PD-1 antibody, nivolumab, patient enrollment for a phase III trial has been completed in a phase III study initiated to compare sorafenib and nivolumab in a first-line setting, and the final results are expected. A phase III trial conducted to compare pembrolizumab and placebo in sorafenib-refractory/intolerant patients revealed that pembrolizumab offered no survival benefit. However, the drug may be expected to be effective when used in combination with other agents. Currently, trials of combined immune checkpoint inhibitor plus immune checkpoint inhibitor and combined immune checkpoint inhibitor plus molecular-targeted agent therapy are ongoing, while some phase III trials have already been completed. In this session, current evidence on systemic therapy for advanced HCC will be reviewed and the trends in the future development of treatments for HCC will be outlined.
C The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. V
All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz351/5582774 by guest on 25 October 2019
Satoshi Kobayashi, Makoto Ueno, Manabu Morimoto Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center
WS1
WORKSHOP 1 : HOW DO WE PROPERLY USE VARIOUS REGIMENS IN CHEMOTHERAPY FOR ADVANCED HCC? WS1
1
Hepatic arterial infusion chemotherapy for hepatocellular carcinoma: currnet status and future perspective
Hepatic arterial infusion chemotherapy (HAIC) is a treatment modality that provides direct delivery of highly concentrated anticancer drugs into tumour-feeding vessels using an intraarterial catheter technique and decreases the systemic distribution through the first-pass effect of the liver. Therefore, HAIC is expected to have strong anticancer effects and mild toxicity, and it has been used mainly for advanced hepatocellular carcinoma (HCC) with macrovascular invasion. Several studies have demonstrated the efficacy and safety of HAIC even after sorafenib (SOR) became a standard treatment for advanced HCC following the result of a phase III study: however, the results were not consistent with each other because of different patients and different treatment regimens. Moreover, no phase III trial was conducted to detect the efficacy of HAIC compared to that of SOR. Based on the results, HAIC could not become a standard treatment for patients with advanced HCC. As a perspective of HAIC, combination treatment containing tyrosine kinase inhibitors (TKIs) such as SOR or lenvatinib (LEN) may be an area to develop. Although LEN has shown non-inferiority to sorafenib in terms of survival, both SOR and LEN have several toxicities. Therefore, SOR and LEN are difficult to combine with other treatments, whereas HAIC could be a candidate because of its mild toxicity. Two prospective randomised trials that evaluated the efficacy of SOR and HAIC combination therapy showed promising results, and a phase III study that tests the efficacy of TKIs and HAIC combination therapy is warranted. Another aspect regarding HAIC to develop may be the treatment for patients with Child-Pugh class B/C disease. Several new chemotherapeutic agents have been developed; however, these treatments, including SOR and LEN, are only intended for patients with Child-Pugh class A disease. HAIC could be developed for such unmet medical needs.
5
Recent advances in systemic therapy for hepatocellular carcinoma
Masafumi Ikeda Department of Hepatobiliary & Pancreatic Oncology, National Cancer Center Hospital East For the treatment of advanced hepatocellular carcinoma (HCC), phase III trials have shown that sorafenib and lenvatinib as first-line treatment agents, and regorafenib, ramcirumab, and cabozantinib as subsequent-line treatment agents in combination with sorafenib, offer survival benefit. At present, sorafenib and lenvatinib for patients with advanced HCC, and regorafenib for patients who are refractory to systemic therapy are reimbursed and can be available in Japan. In the near future, ramucirumab is also expected to be approved for further treatment after second-line treatment of HCC patients with serum AFP levels of 400 ng/mL or more, and data on cabozantinib are also expected to be submitted for approval. Furthermore, the efficacy of immune checkpoint inhibitors is also expected. In regard to the anti-PD-1 antibody, nivolumab, patient enrollment for a phase III trial has been completed in a phase III study initiated to compare sorafenib and nivolumab in a first-line setting, and the final results are expected. A phase III trial conducted to compare pembrolizumab and placebo in sorafenib-refractory/intolerant patients revealed that pembrolizumab offered no survival benefit. However, the drug may be expected to be effective when used in combination with other agents. Currently, trials of combined immune checkpoint inhibitor plus immune checkpoint inhibitor and combined immune checkpoint inhibitor plus molecular-targeted agent therapy are ongoing, while some phase III trials have already been completed. In this session, current evidence on systemic therapy for advanced HCC will be reviewed and the trends in the future development of treatments for HCC will be outlined.
C The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. V
All rights reserved. For permissions, please email: [email protected].
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_6/mdz351/5582774 by guest on 25 October 2019
Satoshi Kobayashi, Makoto Ueno, Manabu Morimoto Department of Gastroenterology, Hepatobiliary and Pancreatic Medical Oncology Division, Kanagawa Cancer Center
WS1