Complete pathological response with diabetic ketoacidosis to the combination of sintilimab and anlotinib in an unresectable hepatocellular carcinoma patient: a case report

Abstract

Most hepatocellular carcinoma (HCC) patients have dismal prognoses because they are already in the advanced stage at the time of initial diagnosis and are unable to undergo upfront surgery. Recent studies of immune checkpoint inhibitors (ICIs) and antiangiogenic agents (AAAs) have shown encouraging results for unresectable HCC (uHCC). Here, we report a patient with uHCC who was treated with a combination of anlotinib and sintilimab (sintilimab 200 mg, intravenous glucose tolerance test, q21d and anlotinib 12 mg, orally, d1–14, q21d), an analog of the combination of lenvatinib and pembrolizumab with much lower cost. The patient with recurrent uHCC was downstaged to resectable disease by the combination therapy. After eight cycles of treatment with anlotinib and sintilimab, the patient underwent a second operation. The histology of the resected mass revealed a major and almost complete pathological response. However, this patient was diagnosed with type I diabetes mellitus with ketoacidosis after nearly 10 cycles of combination treatment with anlotinib and sintilimab. Active follow-ups revealed no signs of local recurrence or distant failure. In conclusion, this case report demonstrated that the combination of anlotinib and sintilimab, one of the strategies combining ICIs with AAAs, showed promising efficacy in the treatment of uHCC patients.

Case Report: A Case of Sintilimab-Induced Cystitis/Ureteritis and Review of Sintilimab-Related Adverse Events

“…For the cases reviewed, the demographic features, clinical manifestations and treatment of irAEs were summarized ( Table 1 ). From these case reports, sintilimab has been shown to induce various immune-associated disorders, including autoimmune diabetes ( 18 , 26 , 30 ), pneumonitis ( 27 , 28 ), pulmonary fibrosis ( 20 ), cytokine release syndrome and multiple organ failure ( 20 , 21 ), myocarditis ( 24 , 29 ), hypothyroid myopathy ( 19 ), myasthenia gravis and myasthenia crisis ( 22 ), paraneoplastic neurological syndrome and enteric neuropathy ( 23 ), psoriasis exacerbation ( 25 ). Some literatures previously indicated that patients with irAEs usually showed a markedly better efficacy than those without irAEs, known as higher overall response rate, longer PFS and better overall survival ( 31 , 32 ).…”

Novel Nanocrystal Injection of Insoluble Drug Anlotinib and Its Antitumor Effects on Hepatocellular Carcinoma

“…Compared with traditional cytotoxic chemotherapeutics, these agents have higher safety and selectivity profiles, and they have benefited many patients who cannot be cured by surgical operations or who are resistant to common chemotherapeutics ( 58 ). Anlotinib can be used clinically for the treatment of locally advanced or metastatic non-small cell lung cancer, but it also offers a new hope for HCC treatment ( 59 , 60 ). Oral administration has good patient compliance and is usually the preferred route of administration of drugs for the treatment of chronic diseases ( 61 ).…”