Case report: Preliminary response to tislelizumab plus S-1 in patients with metastatic gallbladder carcinoma: A report of five cases and a literature review

Abstract

Gallbladder cancer (GBC) and cholangiocarcinoma are common cancers of the biliary system and are associated with a poor prognosis. Surgery and chemotherapy provide limited benefit to patients with advanced biliary tract carcinoma. Novel immunotherapies and molecularly targeted therapies are more effective options; however, few patients benefit and drug resistance is a concern. Here, we report five cases of advanced GBC with either high programmed death-ligand 1 (PD-L1) expression or a high tumor mutation burden (TMB-H). The patients were treated with a combination therapy of tislelizumab and S-1. The tumors were effectively controlled in most patients. One patient developed immune-related pneumonia (irP) during treatment, which resolved after hormone therapy, and the patient underwent surgery. Tislelizumab and S-1 were administered again after surgery; however, recurrent irP required discontinuation, and the tumor progressed after drug withdrawal. These cases demonstrate that combined therapy of anti-programmed cell death protein-1 (PD-1) antibodies and S-1 is a safe and effective regimen with few side effects for GBC patients, especially for sensitive populations (patients with TMB-H, microsatellite instability, deficient mismatch repair, or high expression of PD-L1). To our knowledge, this is the first time that tislelizumab in combination with S-1 has been used to treat patients with advanced GBC.

Keywords: GBC; PD-L1; S-1; immunotharapy; tislelizumab.

Figure 1

CECT and Immunohistochemistry for Case 1. (A, B) Tumor condition at first CECT scan. (C) Immunohistochemistry of PD-L1 expression. (D, E) Tumor conditions after seven cycles of treatment of tislelizumab + S-1. (F) irP after treatment. (G, H) The tumor shrank after continued immunotherapy, but the patient developed irP. (I) New lymph node metastasis. (J) irP developed during postoperative tislelizumab administration. (K) Lung metastasis. (L) irP after administration of nivolumab. CECT, contrast-enhanced computed tomography; PD-L1, Programmed Cell Death-Ligand 1; irP, immune-related pneumonia.

Figure 2

CECT, HE, and Immunohistochemistry for Case 2. (A) Intrahepatic mass at diagnosis. (B) A second intrahepatic mass at diagnosis. (C) Peri-gallbladder condition at diagnosis. (D) Hematoxylin and eosin staining of biopsy tissue (original magnification ×200). (E) Hematoxylin and eosin staining of biopsy tissue (original magnification ×400). (F) PD-L1 staining of biopsy tissue (original magnification ×400). (G) The reduction of the intrahepatic mass after 5 months of treatment. (H) Significant reduction in a second intrahepatic mass after 5 months of treatment. (I) Significant reduction in the peri-gallbladder mass after 5 months of treatment. (J) Persistent reduction of the intrahepatic mass after 18 months of treatment. (K) Persistent reduction in a second intrahepatic mass after 18 months of treatment. (L) Persistent reduction in the peri-gallbladder mass after 18 months of treatment. CECT, contrast-enhanced computed tomography; HE, hematoxylin and eosin; PD-L1, Programmed Cell Death-Ligand 1.

Figure 3

CECT and Macroscopy for Case 3-5. (A) Preoperative tumor conditions of case 3. (B) Postoperative 6 months reexamination of case 3. (C) Postoperative 18 months reexamination of case 3. (D) Preoperative tumor conditions of case 4. (E) Postoperative progression and bile duct dilatation of case 4. (F) Postoperative progression and hilar soft tissue effects of case 4. (G) Postoperative neck metastasis of case 4. (H) Hilar soft tissue shadow slightly reduced after immunotherapy in case 4. (I) Neck tumor disappeared after immunotherapy in case 4. (J) Preoperative tumor conditions of case 5. (K) Postoperative intrahepatic metastasis of case 5. (L) Intrahepatic metastases reduced after immunotherapy in case 5. CECT, contrast-enhanced computed tomography; HE, hematoxylin and eosin; PD-L1, Programmed Cell Death-Ligand 1.

Figure 4

Timelines of Case 1-5. (A) The timeline of case 1. (B) The timeline of case 2. (C) The timeline of case 3. (D) The timeline of case 4. (E) The timeline of case 5.