Journal of Hepatocellular Carcinoma (May 2021)
Clinical Indicators for Long-Term Survival with Immune Checkpoint Therapy in Advanced Hepatocellular Carcinoma
Abstract
Cecilia Monge,1 Changqing Xie,1 Seth M Steinberg,2 Tim F Greten1,3 1Gastrointestinal Malignancies Section, Thoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA; 2Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA; 3NCI CCR Liver Cancer Program, National Institutes of Health, Bethesda, MD, 20892, USACorrespondence: Tim F Greten Tel +1 240-760-6114Email [email protected]: Patients with advanced hepatocellular carcinoma have a dismal prognosis; only a subset of patients with advanced HCC will benefit from treatment with immunotherapy. We searched for clinical characteristics predicting exceptional long-term survival in HCC patients treated with immune checkpoint inhibitors.Methods: We compared clinical characteristics of 59 patients with advanced hepatocellular carcinoma treated with immunotherapy with and without locoregional therapy between 2013– 2019. We compared patients who lived less than 12 months with patients who lived more than 3 years. Traits of short-term (31 patients) and long-term (5 patients) survivors were compared. Patients who died between 12 months and 3 years of starting treatment on protocol were not included in the analysis.Results: Two out of five patients (40%) in the long-term survival group had a partial response (PR) or a complete response (CR) per the modified Response Evaluation Criteria in Solid Tumors (mRECIST), while, of the 31 patients in the short-term survival group, only 2 (6.5%) had a CR or PR. Two of the 5 patients with a long-term survival had immune-related adverse events grade 3 or 4 (IrAEs-3/4). None of the patients in the short-term survival group had IrAEs-3/4. The patients, who presented with IrAEs-3/4, which included colitis and adrenal insufficiency, continued to have a response off treatment. The median overall survival (OS) was 11.8 months (95% CI: 7.8– 15.4 months), with a 12-month OS of 46.6% (95% CI: 33.4– 58.8%) and a 3-year OS of 12.5% (95% CI: 5.0– 23.7%).Conclusion: We found a possible association between immune-related adverse events grade 3 and 4 and long-term survival in patients with advanced HCC. The cases in our analysis represent extraordinary defiance of the usual predicted dismal course of advanced HCC.Keywords: hepatocellular carcinoma, immunotherapy, long-term overall survival, immune-related adverse events, tremelimumab, durvalumab
