Combination toripalimab and bevacizumab for an elderly urothelial carcinoma patient with brain metastasis who failed rapidly after radiotherapy: a case report and literature review

Abstract

Brain metastasis is a rare refractory event in patients with urothelial carcinoma. Platinum-based chemotherapy is the recommended first-line standard therapy for all metastasis urothelial carcinoma patients eligible for cisplatin or carboplatin. Patients ineligible for platinum may receive immunotherapy. No clear evidence exists that UC with brain metastasis is sensitive to immunotherapy, and the optimal treatment for patients with BM is uncertain. We evaluated the safety and efficacy of combined immunotherapy and antivascular therapy in an elderly patient with urothelial carcinoma with brain metastasis, and summarize the currently available evidence. First, she underwent a left nephrectomy and left ureterectomy and recovered well postoperatively. The postoperative pathologic findings were consistent with urothelial carcinoma. Approximately 2 years later, the patient developed impaired limb movement on the right side and underwent MRI, which revealed lesions in the left frontal lobe and suggested brain metastasis. The brain metastasis responded to local radiotherapy but progressed again in a short time. Then, the patient was administered toripalimab at 240 mg combined with bevacizumab at 300 mg every 3 weeks. After 1cycle of treatment, the patient achieved a quick response, and symptoms improved significantly. Repeat evaluation imaging demonstrated that the lesions in the brain and lung were significantly smaller and evaluation showed partial response. The treatment was well tolerated and the patient remained in partial response until the last follow-up by July 2022, 6 months after the initiation of treatment. This case suggests that immune checkpoint blockade combined with antivascular therapy might be a new possibility for patients with metastatic urothelial carcinoma, including brain metastases.

Combination of anlotinib and toripalimab for an advanced biliary tract cancer patient with high Eastern Cooperative Oncology Group performance status: a case report

“…The demand for more effective treatment options is apparent based on the poor prognosis currently reported for patients with BTCs [15]. With the rapid development of ICIs, which can activate effector T cells and increase the cytotoxicity and infiltration of effector T cells to normalize tumor vasculature [16], several trials of combining ICIs with chemotherapy are underway, such as KEYNOTE-966, ABC-02, and TOPAZ-1 [17]. However, patients with recurrent or advanced BTCs often experience a rapid decline in performance status, and cannot tolerate chemotherapy [6].…”

“…Toripalimab, a humanized IgG4K mAb against PD-1, has a high binding affinity. A study showed the different binding orientation of toripalimab compared with other ICIs, which binds PD-1 mainly on a loop that contributes to multiple interactions with programmed death-ligand 1 [16,19]. Sheng et al [20] reported the good tolerability of toripalimab, which may make it possible to use concurrently with other anticancer drugs.…”