Nivolumab in Cholangiocarcinoma: A Case Report

Abstract

Cholangiocarcinoma is a rare neoplasm that is composed of mutated epithelial cells that originate in the bile ducts.. No potentially curative treatment exists except surgery, but most people have advanced stage disease at presentation and are inoperable at the time of diagnosis. For non-resectable cases due to distal metastasis, the 5-year survival rate is 0%. For those with advanced disease and chemotherapy, a gemcitabine-based therapy has shown some efficacy. Nivolumab, a fully human immunoglobulin G4 programmed death—1 (PD-1) immune checkpoint inhibitor antibody, has been demonstrated to restore T-cell immune activity in treating various malignancies. We report a case in which Nivolumab was used for advanced cholangiocarcinoma with clinically significant response. A 82 year old female (ECOG 2) presented with progressive abdominal pain and nausea and vomiting. CT scan of the abdomen revealed a 6 x 4 cm hepatic mass, suspicious for cholangiocarcinoma with peritoneal metastasis. FNA of the liver lesion was performed which returned positive for poorly differentiated adenocarcinoma staining positive with CK7, CK19, and focal staining with CK17 and CK20. Immunohistochemical stains negative for CDx2, GATA3, Glypican 3, TTF1 and CA19-9 more consistent with pancreas and biliary origin. The patient was treated with gemcitabine with capecitabine for 16 cycles. CT scan after completion showed overall increased size of intrahepatic cholangiocarcinoma (9.3 x 3.9 cm from 8 x 3.3 cm), peritoneal carcinomatosis and numerous small omental implants. After discussion with the patient, the plan to start a PD-1 inhibitor was offered. The patient was started on Nivolumab and now after 27 cycles, which was well tolerated, interval CT scans have shown regression in the size of the tumor. CT scan after the 12th cycle showed measurable decrease in hepatic tumor (8.5 x 3.3 cm from previously 9.7 x 4.2 cm) and portacaval lymph node (1.6 cm x 0.7 cm from 1.9 x 1 cm). Repeat CT scan after 24th cycle of Nivolumab, showed further measurable decrease in hepatic tumor(7.3 x 3.2 cm, previously 8.5 x 3.3 cm) and ascites. Cholangiocarcinoma usually yields an extremely poor prognosis and options are currently limited. Nivolumab appears to be efficacious in patients with advanced cholangiocarcinoma with minimal side effects. Further research needs to be performed to fully assess its potential as a therapeutic option.1329_A.tif Figure 1: No Caption available.1329_B.tif Figure 2: No Caption available.