Role of Targeted Therapies in Advanced Cholangiocarcinoma - Episode 1

Advanced Cholangiocarcinoma: Current Treatment Landscape

Saeed Sadeghi, MD: The current landscape for metastatic cholangiocarcinoma is somewhat limited. At this time, for patients in the first-line setting, the standard-of-care regimen is still the ABC-02 regimen of gemcitabine and cisplatin that has been in practice for some time. The ABC-02 trial demonstrated an overall survival benefit for the combination—11.2 months. For patients who have progressed following first-line therapy, unfortunately we don’t have a true standard of care.

The closest we have to that is the recently presented ABC06 trial that looked at the combination of FOLFOX [5-fluororacil, leucovorin calcium, oxaliplatin] plus supportive care compared with supportive care alone. The trial did show a benefit in overall survival in the second-line setting—6.2 months—when compared with placebo. Because it was a phase 3 trial, it’s considered by many to be the standard of care in the second-line setting. Beyond this, other chemotherapy combination regimens have been studied. We don’t have high-level evidence for other regimens, and there’s certainly a need for additional therapeutics for this disease.

In the past few years, there’s been a great deal of research and work done identifying various mutations that occur in cholangiocarcinoma. These mutations and changes are potentially actionable, and this has really led to the development of novel therapeutics that can be beneficial in a subset of patients.

With a better understanding of the molecular pathways that are involved in cholangiocarcinoma, we have the ability to design drugs that are highly selective for specific pathways. This is beneficial because by doing this, you can potentially limit the toxicities of compounds and avoid additional toxicities that may occur because of off-target effects from the therapies.

Transcript edited for clarity.