Abstract 3627: Organ-specific differential responses to immune checkpoint inhibitors in patients with advanced hepatocellular carcinoma
Authors: Li-Chun Lu, Chiun Hsu, Yu-Yun Shao, Yee Chao, Chia-Jui Yen, I-Lun Shih, Yi-Ping Hung, Chun-Jung Chang, Ying-Chun Shen, Jhe-Cyuan Guo, Tsung-hao Liu, Chih-Hung Hsu, Ann-Lii Cheng
Journal: Cancer Research (2018)

Abstract Background: Immune checkpoints inhibitors (ICIs) such as anti-PD-1/PD-L1 monoclonal antibodies exhibit significant clinical activity in patients with advanced hepatocellular carcinoma (HCC). Immune microenvironments of different organs are often different and may affect the efficacy of immunotherapy. The study explores whether tumor response to ICIs of HCC may vary among different organs. Patients and Methods: We reviewed patients with advanced HCC who had received anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy, alone or in combination, in 3 medical centers in Taiwan. Patients with measurable diseases were enrolled. An organ-specific response criteria, modified from RECIST 1.1, allowing a maximum of 5 measurable lesions per organ system, was used to evaluate the responses to ICIs for tumors of individual organ system. The organ-specific complete responses (CR), partial responses (PR), stable diseases (SD), or progressive diseases (PD) were determined for individual organ system. Results: A total of 76 patients (Male: Female= 62: 14, median age of 59.1 years) with advanced HCC were enrolled. Among them, 51 (67.1%) and 12 (15.8%) patients had chronic hepatitis B virus or chronic hepatitis C infection. The ICI treatments included anti-PD-1 or anti-PD-L1 alone, anti-CTLA4 alone, and anti-PD-1/PD-L1 plus anti-CTLA4 combination in 59, 1, and 16 patients; 20 and 56 patients had received ICIs as first-line or ≥ 2nd-line therapy. The overall response rate (RR) by RECIST 1.1 was 28.9%. Fifty-nine, 34, 18, and 18 patients who had measurable hepatic tumors, lung, lymph node, and intra-abdomen metastases were subject to organ-specific response evaluation. Organ-specific RRs of hepatic tumors, lung, lymph node, and intra-abdomen metastases, were 23.7, 41.2, 27.8, and 38.9%, respectively. Among 39 patients who had both hepatic and extrahepatic tumors, 16 had significant differential responses between hepatic and extrahepatic tumors: 12 of them had disease control (CR/PR/SD) in extrahepatic tumors and PD in hepatic tumors, and 4 exhibited disease control in hepatic tumors and PD in extrahepatic tumors (p=0.046). Moreover, in 16 patients with only evaluable hepatic tumors and lung metastases, 8 had disease control in lung metastases and PD in hepatic tumors, and none experienced disease control in liver tumors and PD in lung metastases (p=0.005). Conclusions: The hepatic tumors of HCC are less responsive to ICIs than the extrahepatic lesions. Lung metastases show best response to ICIs. The underlying mechanism warrants further investigation. (This work is supported by grants from the Ministry of Science and Technology, Taiwan, MOST 106-2314-B-002-210). Citation Format: Li-Chun Lu, Chiun Hsu, Yu-Yun Shao, Yee Chao, Chia-Jui Yen, I-Lun Shih, Yi-Ping Hung, Chun-Jung Chang, Ying-Chun Shen, Jhe-Cyuan Guo, Tsung-hao Liu, Chih-Hung Hsu, Ann-Lii Cheng. Organ-specific differential responses to immune checkpoint inhibitors in patients with advanced hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3627.