A Case of Hepatocellular Carcinoma Successfully Resumed Atezolizumab and Bevacizumab After Associated Grade 3 Diarrhea and Grade 2 Colitis: Case Report and Literature Review

Abstract Systemic chemotherapy has shown a significant survival benefit in patients with hepatocellular carcinoma (HCC). However, it is associated with various immune-related adverse events (irAEs). We report a case with grade 3 diarrhea and grade 2 colitis following systemic chemotherapy, successfully treated with prednisolone. An 89-year-old man was incidentally detected with a 140-mm hypervascular intrahepatic nodule on contrast-enhanced computed tomography (CECT). Washout of the contrast medium was also detected, and protein induced by vitamin K deficiency or antagonists-II (PIVKA-II) was elevated. Since the Albumin–Bilirubin (ALBI) grade was 2a without any distant metastasis, transarterial chemoembolization (TACE) was performed to treat the HCC, but several intrahepatic nodules were seen in both lobes. Therefore, the patient was treated with lenvatinib for 1 year and 4 months. A complete response according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria was achieved in 2 months; however, multiple hypervascular nodules were detected again. Since the ALBI grade was 1, a second round of chemotherapy with atezolizumab and bevacizumab was initiated. Although a complete response was achieved, the therapy was discontinued due to grade 3 diarrhea and grade 2 colitis after the sixth course. Based on the stool analysis and culture, CECT, and colonoscopy, the diagnosis was atezolizumab-associated colitis. Diarrhea was controlled following the oral administration of 0.5 mg/kg/day of prednisolone, and atezolizumab-bevacizumab therapy was successfully reinitiated without recurrence of colitis. The management of irAEs is important for a significant survival benefit. Systemic chemotherapy with atezolizumab and bevacizumab can be resumed despite a grade 3 irAE due to atezolizumab.

[1]  H. Yoshiji,et al.  Liver-related events after direct-acting antiviral therapy in patients with hepatitis C virus-associated cirrhosis , 2022, Journal of Gastroenterology.

[2]  C. Schneider,et al.  Durable Metastatic Melanoma Remission Following Pembrolizumab and Radiotherapy: A Case Report of Prophylactic Immunosuppression in a Patient with Myasthenia Gravis and Immune-Mediated Colitis , 2021, Frontiers in Immunology.

[3]  Zhanjun Guo,et al.  Correlation Between Immune-Related Adverse Events and Prognosis in Hepatocellular Carcinoma Patients Treated With Immune Checkpoint Inhibitors , 2021, Frontiers in Immunology.

[4]  M. M. van den Heuvel,et al.  Mechanisms of Immune Checkpoint Inhibitor-Mediated Colitis , 2021, Frontiers in Immunology.

[5]  Jana G Hashash,et al.  Diagnosis and Management of Immune Checkpoint Inhibitor Colitis. , 2021, Gastroenterology & hepatology.

[6]  A. Gasbarrini,et al.  Safety, Efficacy, and Pharmacodynamics of Tremelimumab Plus Durvalumab for Patients With Unresectable Hepatocellular Carcinoma: Randomized Expansion of a Phase I/II Study , 2021, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  M. Kurosaki,et al.  The Real-World Data in Japanese Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib from a Nationwide Multicenter Study , 2021, Cancers.

[8]  T. Murakami,et al.  Management of Hepatocellular Carcinoma in Japan: JSH Consensus Statements and Recommendations 2021 Update , 2021, Liver Cancer.

[9]  F. Piscaglia,et al.  Experience with regorafenib in the treatment of hepatocellular carcinoma , 2021, Therapeutic advances in gastroenterology.

[10]  L. Rimassa,et al.  Impact of corticosteroid therapy on the outcomes of hepatocellular carcinoma treated with immune checkpoint inhibitor therapy , 2020, Journal for ImmunoTherapy of Cancer.

[11]  H. Ogata,et al.  Clinical, Endoscopic, and Pathological Characteristics of Immune Checkpoint Inhibitor-Induced Gastroenterocolitis , 2020, Digestive Diseases and Sciences.

[12]  J. Marrero,et al.  Trial Design and Endpoints in Hepatocellular Carcinoma: AASLD Consensus Conference , 2020, Hepatology.

[13]  A. Cohen,et al.  Immune Checkpoint Inhibitor Rechallenge After Immune-Related Adverse Events in Patients With Cancer. , 2020, JAMA oncology.

[14]  Matthew J. Frigault,et al.  NCCN Guidelines Insights: Management of Immunotherapy-Related Toxicities, Version 1.2020. , 2020, Journal of the National Comprehensive Cancer Network : JNCCN.

[15]  F. Farraye,et al.  "Immune checkpoint inhibitor-related luminal GI adverse events". , 2019, Gastrointestinal endoscopy.

[16]  W. Huh,et al.  Combination checkpoint inhibitor therapy induces multiple immune major related adverse events in the treatment of vaginal melanoma: A cautionary case report , 2019, Gynecologic oncology reports.

[17]  H. Iijima,et al.  Immune checkpoint inhibitor-induced diarrhea/colitis: Endoscopic and pathologic findings , 2019, World journal of gastrointestinal pathophysiology.

[18]  P. Brastianos,et al.  Concurrent therapy with immune checkpoint inhibitors and TNFα blockade in patients with gastrointestinal immune-related adverse events , 2019, Journal of Immunotherapy for Cancer.

[19]  O. Lambotte,et al.  Evaluation of Readministration of Immune Checkpoint Inhibitors After Immune-Related Adverse Events in Patients With Cancer. , 2019, JAMA oncology.

[20]  Jianjun Gao,et al.  Resumption of Immune Checkpoint Inhibitor Therapy After Immune-Mediated Colitis , 2019, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  N. Malhotra,et al.  Immune checkpoint inhibitor-induced colitis: A comprehensive review , 2019, World journal of clinical cases.

[22]  N. Kato,et al.  Predominance of regorafenib over sorafenib: Restoration of membrane‐bound MICA in hepatocellular carcinoma cells , 2018, Journal of gastroenterology and hepatology.

[23]  Douglas B. Johnson,et al.  Incidence of immune checkpoint inhibitor-related colitis in solid tumor patients: A systematic review and meta-analysis , 2017, Oncoimmunology.

[24]  K. Kerr,et al.  Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. , 2017, Annals of oncology : official journal of the European Society for Medical Oncology.

[25]  J. Soria,et al.  Immune-related adverse events with immune checkpoint blockade: a comprehensive review. , 2016, European journal of cancer.

[26]  J. Kirkwood,et al.  Baseline circulating IL-17 predicts toxicity while TGF-β1 and IL-10 are prognostic of relapse in ipilimumab neoadjuvant therapy of melanoma , 2015, Journal of Immunotherapy for Cancer.

[27]  Y. Osaki,et al.  Non-B, non-C hepatocellular carcinoma (Review). , 2013, International journal of oncology.

[28]  H. El‐Serag,et al.  Epidemiology of viral hepatitis and hepatocellular carcinoma. , 2012, Gastroenterology.

[29]  M. Imamura,et al.  Recent trend of clinical features in patients with hepatocellular carcinoma , 2012, Hepatology research : the official journal of the Japan Society of Hepatology.

[30]  A. Ribas,et al.  CTLA4 blockade increases Th17 cells in patients with metastatic melanoma , 2009, Journal of Translational Medicine.