摘要

肝細胞癌是臺灣常見的癌症之一，早期症狀不明顯，導致多數病人在診斷時已屬中晚期，預後不佳。在過去，酪胺酸酶抑制劑 (tyrosine kinase inhibitor, TKI) 一直是晚期肝細胞癌僅有的全身性治療選擇。而自免疫療法問世後，雙重免疫治療已被證實可以改善晚期肝細胞癌的預後。根據IMbrave150 的三期試驗結果，atezolizumab 與bevacizumab 的合併療法相較於sorafenib，可明顯改善整體存活期和無惡化存活期，但同時也伴隨較強的副作用。而根據HIMALAYA 的三期試驗結果，tremelimumab 與durvalumab 的合併療法相較於durvalumab 的單一療法或是sorafenib，也可改善整體存活期。此外，根據一篇network meta-analysis 的文獻分析，可發現atezolizumab與bevacizumab 以及tremelimumab 與durvalumab 的兩種治療組合相較於安慰劑或是TKI 皆可改善存活率。然而，由於atezolizumab 與bevacizumab 的合併療法因不良反應而導致停藥的機率最高，相較之下tremelimumab 與durvalumab 發生不良反應的風險則較低，可能更加適合身體狀況不甚理想的病人。

 

ABSTRACT

Hepatocellular carcinoma (HCC) is among the most common cancers in Taiwan. However, early diagnosis is challenging because most patients are asymptomatic in the initial stages, and the disease is often diagnosed at an intermediate or advanced stage with a poor prognosis. Tyrosine kinase inhibitors (TKIs) have been used as first-line treatments for over a decade. Immunotherapy has benefitted patients with advanced HCC. The results of the IMbrave150 clinical trial showed treatment with atezolizumab in combination with bevacizumab significantly increased overall survival (OS) and progression-free survival compared with sorafenib but also resulted in a higher incidence of adverse events. Treatment with a combination of tremelimumab and durvalumab led to increased OS compared with either durvalumab monotherapy or sorafenib. Moreover, these combination therapies improved survival outcomes compared with placebos or TKIs according to a network meta-analysis. The combination therapies of atezolizumab-bevacizumab and durvalumab-tremelimumab were associated with higher and lower probabilities of adverse events, respectively.

 

 

Submitted for publication: 2024.9.23; Accepted for publication: 2025.3.19