AB023. S4-3. Down-staging locally advanced disease

Abstract: Cholangiocarcinoma is often diagnosed at an advanced stage and carries with it a poor prognosis. Surgical resection is the only curative therapy available for this disease and can be offered upfront in rare instances. The majority of patients with intrahepatic cholangiocarcinoma typically have large tumors or multifocal disease which preclude immediate resection. New approaches to locally advanced cholangiocarcinoma include neoadjuvant chemotherapy or targeted therapies that allow for down-staging disease. Combination chemotherapy with gemcitabine and cisplatin remains the standard of care for treating advanced cholangiocarcinoma. Chemo-intensification with triplet combinations such as gemcitabine, cisplatin and nab-paclitaxel have also shown promise in the palliative setting with a phase II study of 60 patients demonstrating an overall survival of over 19 months. Interestingly, in this study, 12 patients (20%) were converted from unresectable disease and underwent successful surgical resection. Two of these patients also demonstrated a pathologic complete response, suggesting a utility to this triplet chemotherapy regimen in the neoadjuvant setting. To this end, an ongoing multicenter study is investigating gemcitabine, cisplatin, and nab-paclitaxel in high-risk or borderline resectable cholangiocarcinoma to better understand its potential for down-staging disease and for offering these patients potentially curative therapy. Furthermore, as we identify the actionable mutations in patients with cholangiocarcinoma through next generation sequencing, consideration should be given to the role of targeted approaches based on individual molecular profiles in the neoadjuvant setting. As we better identify personalized approaches to down-staging locally advanced disease, the hope would be to increase the surgical resection and cure rate for this otherwise deadly malignancy.

Keywords: Neoadjuvant therapy; locally advanced cholangiocarcinoma