What is your preferred second line of treatment after progression on cisplatin/gemcitabine for advanced or metastatic cholangiocarcinoma?
What is your choice for second line treatment for advanced/metastatic cholangiocarcinoma following progression on gemcitabine/cisplatin?
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After progression on the front-line standard of gemcitabine and cisplatin (ABC-02, Valle et al. NEJM 2010), there is not an established second-line standard of care. There are several small prospective studies as well as some retrospective data that are indeed conflicting regarding the true efficacy of chemotherapy in the second-line setting in this population.
In my practice, I often try to find a clinical trial for bile duct cancer. At the time of presentation, I will have the tumor in question genotyped using next generation sequencing. These data are important both for standard of care options as well as investigational options in the second-line. For example, a bile duct cancer with mismatch repair deficiency/ microsatellite high phenotype should receive pembrolizumab as a standard of care or an immune checkpoint inhibitor in the context of a clinical trial. Sequencing of bile duct tumors may also reveal a host of actionable mutations that are accessible on investigational clinical studies, including but not limited to alterations in IDH1/2, FGFR2, ERBB2, BRCA, MDM2, and NTRK. In addition, there are several other rational clinical trials offered across the United States that are evaluating novel treatments for bile duct cancer.
In the absence of a trial, I typically recommend a move to a fluoropyrimidine-based regimen such as capecitabine monotherapy, or combination treatment such as FOLFIRI or gemcitabine/capecitabine. I base my patient discussion on the physiological fitness of the patient and the potential side effects profile. Regarding the use of second-line platinum, I often only use this in patients who had an initial excellent response to prior cisplatin and have been off prior cisplatin for an extended period of time. In very select instances for incurable liver-limited or locally advanced disease, I might consider a regional approach. Finally, for patients who have diminished performance status, I would also discuss best supportive care.