Update on Emerging Systemic Therapies in Cholangiocarcinoma

TOP - May 2022 Vol 15, No 3 - Cholangiocarcinoma

During the 2022 Cholangiocarcinoma Foundation annual meeting, Lipika Goyal, MD, MPhil, Assistant Professor of Medicine, Harvard Medical School, and Lead, Liver Cancer Research Program, Massachusetts General Hospital Cancer Center, Boston, presented a clinical update on emerging systemic therapies in cholangiocarcinoma (CCA).

The treatment landscape for CCA has changed dramatically in the past decade, Dr Goyal said. She attributed the recent advancements to a growing understanding of CCA disease biology that has led to the identification of actionable genetic alterations and a more rational clinical trials design. Dr Goyal highlighted the results and specific study designs of several studies in biliary tract cancer.

1. Based on results of the BILCAP study, adjuvant capecitabine therapy is used in patients with resected biliary tract cancer, but this does not improve overall survival (OS) compared with surgery alone.1

2. According to the phase 3 clinical trial results presented at the 2022 ASCO GI Cancers Symposium, adjuvant therapy with S-1, an oral fluoropyrimidine derivative, improved OS compared with surgery alone (77.1% vs 67.6%; hazard ratio [HR], 0.694; P = .008) in patients with resected biliary tract cancer.2

3. For targeted therapies, “there are a lot of different types of trials,” Dr Goyal said. Target-specific CCA trials “study mutations or alterations that are somewhat common, such as FGFR2 fusions and IDH1 mutations in intrahepatic CCA.”

By contrast, target-specific all-comer basket trials refer to clinical trial design in which a targeted therapy is evaluated for multiple diseases that share common molecular alterations, and this design is typically used “when you have a more rare frequency of the mutations.”

Finally, biliary umbrella clinical trials with target-specific arms refer to clinical trial design in which multiple targeted therapies are evaluated for a single disease,3 “where patients with BTCs [biliary tract cancers] get profiled, and then, depending on what alteration they have, they can go into one of many arms of a trial.”

For example, the open-label, phase 2a, multiple-basket MyPathway study is evaluating the dual anti-HER2 regimen of pertuzumab plus trastuzumab in patients with metastatic biliary tract cancers and HER2 amplification, overexpression, or both. At median follow-up of 8.1 months, 9 of 39 patients achieved a partial response, for an objective response rate of 23%.4

4. Based on results of the phase 3 TOPAZ-1 clinical trial presented at the 2022 ASCO GI Cancers Symposium, the addition of the PD-L1 inhibitor durvalumab to the chemotherapy backbone of gemcitabine plus cisplatin as first-line therapy in advanced biliary tract cancer significantly improved the OS versus gemcitabine plus cisplatin alone (12.8 vs 11.6 months; HR, 0.80; P = .021), without significantly more adverse events.5

Commenting on the TOPAZ-1 study, Dr Goyal noted, “There is a tail on the survival curve, where there is a population of patients who are getting significant benefit at 2 years, even though the actual difference in median survival was not too different. We are encouraged by these data, and this is the new standard.”

Dr Goyal urged attendees to feel “hope and excitement, in terms of all the progress made, in the treatment of cholangiocarcinoma: to feel proud of where you are, to be grateful for where you are.”


  1. Primrose JN, Fox RP, Palmer DH, et al; for the BILCAP study group. Capecitabine compared with observation in resected biliary tract cancer. Lancet Oncol. 2019;20:663-673.
  2. Ikeda M, Nakachi K, Konishi M, et al. Adjuvant S-1 versus observation in curatively resected biliary tract cancer: a phase III trial (JCOG1202: ASCOT). Presented at ASCO GI Cancers Symposium; January 20-22, 2022; San Francisco, CA. Abstract 382.
  3. Park JJH, Hsu G, Siden EG, et al. An overview of precision oncology basket and umbrella trials for clinicians. CA Cancer J Clin. 2020;70:125-137.
  4. Javle M, Borad MJ, Azad NS, et al. Pertuzumab and trastuzumab for HER2-positive, metastatic biliary tract cancer (MyPathway): a multicentre, open-label, phase 2a, multiple basket study. Lancet Oncol. 2021;22:1290-1300.
  5. Oh DY, He AR, Qin S, et al. A phase 3 randomized, double-blind, placebo-controlled study of durvalumab in combination with gemcitabine plus cisplatin in patients with advanced biliary tract cancer: TOPAZ-1. Presented at ASCO GI Cancers Symposium; January 20-22, 2022; San Francisco, CA.
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Last modified: May 6, 2022