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Differential Organ-Specific Tumor Response to Immune Checkpoint Inhibitors in Hepatocellular Carcinoma
Li-Chun Lu1,2,3, Chiun Hsu1,2, Yu-Yun Shao1,2,3
1Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan.
Background And Aims:
Immune checkpoint inhibitors (ICIs) exhibit significant clinical activity in patients with advanced hepatocellular carcinoma (HCC). This study explored whether tumor response to ICIs in HCC varies among different organs.
Methods:
We reviewed the data of patients with advanced HCC who had received ICIs. Patients with measurable diseases were enrolled. Organ-specific response criteria, adapted from RECIST 1.1 and immune-related RECIST, were used to evaluate the objective response to ICIs in tumors located in the liver, lung, lymph node, and other intra-abdominal sites.
Results:
Of the 75 enrolled patients with advanced HCC, 51 and 11 patients had chronic hepatitis B virus and chronic hepatitis C virus infection, respectively. Regarding ICI treatment, 58, 1, and 16 patients had undergone anti-PD-1/anti-PD-L1 monoclonal antibody (mAb) alone, anti-CTLA4 mAb alone, and anti-PD-1 mAb plus anti-CTLA4 mAb, respectively; 20 and 55 patients had received ICIs as first-line or ≥second-line therapy. The overall objective response rate (ORR) was 28.0%. In total, 58, 34, 19, and 18 patients had measurable hepatic tumors and lung, lymph node, and other intra-abdominal metastases, and the corresponding organ-specific ORRs were 22.4, 41.2, 26.3, and 38.9%, respectively. Of the 39 patients who had both hepatic and extrahepatic tumors, 12 had disease control in extrahepatic tumors while progressive disease (PD) in hepatic tumors, whereas only 4 exhibited disease control in hepatic tumors while PD in extrahepatic tumors (p = 0.046, McNemar test). Of the 16 patients with only evaluable tumors in the liver and lungs at baseline, 8 had disease control in the lungs while PD in the liver, and none experienced disease control in the liver while PD in the lungs (p = 0.005).
Conclusions:
The hepatic tumors of HCC may be less responsive to ICIs than extrahepatic lesions. Lung metastases responded most favorably to ICIs. The mechanisms underlying this differential response to ICIs warrant further investigation.