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.

Significance of the autoantibody assay in predicting the development of immune‐related adverse events in patients receiving atezolizumab plus bevacizumab combination therapy for unresectable hepatocellular carcinoma

“…20,21 The incidence rate of irAEs is not high, but in patients with severe irAEs, continuing AB therapy could be difficult and could lead to the deterioration of their general condition. [9][10][11][12][13] In addition, DT combination therapy, which has been administered for u-HCC since 2023, is reported to be associated with a higher incidence of irAEs than AB therapy. 22 Immune-related AEs can significantly affect quality of life and can even be life-threatening.…”

“…The median numbers of doses of atezolizumab and bevacizumab were 5 (2-33) and 5 (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21), respectively. The overall median PFS was 31 weeks (Figure 2a).…”

“…7 The incidence rate of irAEs has been reported to be 30% in patients receiving PD-1/PD-L1 inhibitors. [8][9][10][11][12] However, only five case reports on the irAE development in patients receiving AB therapy have been published. [9][10][11][12][13] Studies have reported that the presence of RF and thyroid autoantibodies at baseline could be associated with irAE development in patients with other types of carcinomas.…”

“…[8][9][10][11][12] However, only five case reports on the irAE development in patients receiving AB therapy have been published. [9][10][11][12][13] Studies have reported that the presence of RF and thyroid autoantibodies at baseline could be associated with irAE development in patients with other types of carcinomas. 14,15 Moreover, smoking, high body mass index, history of autoimmune diseases, and use of concomitant medications such as proton pump inhibitors and nonsteroidal anti-inflammatory drugs might be also associated with irAE development.…”

“…In particular, 43% of the patients presented with grade 3 or 4 AEs and 2% with grade 5 AEs 7 . The incidence rate of irAEs has been reported to be 30% in patients receiving PD‐1/PD‐L1 inhibitors 8–12 . However, only five case reports on the irAE development in patients receiving AB therapy have been published 9–13 …”