Targeted Therapies Offer Hope for Cholangiocarcinoma

In an interview with Targeted Oncology, Arndt Vogel, MD, PhD, professor and clinician scientist in the Division of Gastroenterology and Hepatology at the University of Toronto, discusses the treatment landscape in biliary tract cancer.

Biliary tract cancer, including cholangiocarcinoma, is a devastating disease with a very poor prognosis. A review of recent phase 3 clinical trials shows that the median overall survival for patients is only around 1 year, according to Dr Vogel. This highlights the urgent need for more effective treatments.

One of the challenges in treating cholangiocarcinoma is its resistance to chemotherapy. While chemotherapy can improve survival to some extent, studies have shown that more aggressive triplet chemotherapy regimens don't provide a significant survival advantage over standard doublet chemotherapy. This indicates that we need to look beyond traditional chemotherapy to make meaningful progress.

A major advancement in our understanding of cholangiocarcinoma has come from a better understanding of its genetic mutations. We now know there are many actionable targets in biliary tract cancer, including HER2. Because of this, comprehensive molecular sequencing is a crucial step in the treatment pathway. This allows oncologists to identify specific genetic alterations and, in the second-line setting, treat patients with targeted therapies.

In the first-line setting, the standard of care has evolved to include immunotherapy combined with chemotherapy. However, this combination offers a modest benefit, extending survival by only about 6 weeks. This shows that while we are making small steps forward, there is still a long way to go.

The challenge with assessing the true benefit of these newer targeted therapies is a lack of robust evidence from large-scale clinical trials. Many of these therapies have only been studied in phase 2 trials, which are typically single-arm studies without a control group. This makes it difficult to definitively quantify the absolute survival benefit of a particular treatment. Without a control arm, it's hard to separate the effects of the treatment from other factors that might influence a patient's prognosis.

Despite this limitation, the data from phase 2 studies are highly encouraging. The results consistently show high response rates and significantly long progression-free survival in patients treated with these targeted therapies. While we can't define the exact survival benefit, the consistent and compelling data from these studies provide a strong conviction that these targeted therapies are improving outcomes for patients with cholangiocarcinoma. This evidence, even from phase 2 trials, makes researchers very confident that they are on the right path toward better treatment options.