Liao Highlights Treatment Selection Considerations and Key Data in Biliary Tract Cancer


Chih-Yi Liao, MD, discusses the treatment landscape of advanced biliary tract cancer and outlines therapy selection factors.

Chih-Yi Liao, MD

Chih-Yi Liao, MD

The treatment paradigm of advanced biliary tract cancer (BTC) has expanded rapidly in recent years, adding additional options for patients that require careful consideration of a variety of factors when selecting the optimal therapy, according to Chih-Yi Liao, MD.

“Systemic therapies for BTC are [leading us into] a very exciting but also complicated treatment landscape,” Liao said in an interview with OncLive®. “We’ve seen approvals for first-line immunotherapy plus the gemcitabine/cisplatin backbone, [including] gemcitabine/cisplatin plus pembrolizumab [Keytruda] and gemcitabine/cisplatin plus durvalumab [Imfinzi]. In the second line and beyond, we’re seeing an emerging role for multiple targeted therapies [such as] IDH inhibitors, FGFR inhibitors, HER2-targeted therapies, BRAF-targeted therapies, and [more]. It’s really becoming a very complicated treatment landscape.”

In September 2022, the FDA approved durvalumab in combination with gemcitabine and cisplatin for the treatment of adult patients with locally advanced or metastatic BTC. The decision was supported by findings from the phase 3 TOPAZ-1 trial (NCT03875235), which demonstrated that patients who received durvalumab plus chemotherapy experienced a median overall survival (OS) of 12.8 months (95% CI, 11.1-14.0) vs 11.5 months (95% CI, 10.1-12.5) among those who received chemotherapy alone (HR, 0.80; 95% CI, 0.66-0.97; =.021). The median progression-free survival was 7.2 months (95% CI, 6.7-7.4) vs 5.7 months (95% CI, 5.6-6.7), respectively (HR, 0.75; 95% CI, 0.63-0.89; = .001).1

In October 2023, the FDA approved pembrolizumab with gemcitabine and cisplatin for the treatment of patients with locally advanced unresectable or metastatic BTC. The approval was supported by findings from the phase 3 KEYNOTE-966 trial (NCT04003636), which showed that the median OS with pembrolizumab plus chemotherapy was 12.7 months (95% CI, 11.5-13.6) vs 10.9 months (95% CI, 9.9-11.6) with chemotherapy alone (HR, 0.83; 95% CI, 0.72-0.95; one-sided =.0034).2

In the interview, Liao, associate director, Gastrointestinal Oncology, co-director, Neuroendocrine Tumor Program, and assistant professor of medicine at UChicago Medicine in Illinois, discussed the current and future treatment paradigm of advanced BTC shared during a recent State of the Science Summit™ on gastrointestinal cancer, which he chaired.

OncLive: What is the role of molecular testing in BTC and when would you use a liquid vs tissue-based testing technique?

Liao: Molecular testing is essential for BTC because there are now so many approved targeted therapies, especially in the advanced metastatic setting. Most of these are in the second line and beyond, but trials are investigating targeted therapies in the first-line setting and those data are not out yet.

I like to have my molecular testing results as soon as possible to plan ahead. I tend to order [the test] when I first meet the patient, when they’re first diagnosed, or even when they’re still [receiving] first-line therapy. Even if it doesn’t impact my first-line therapy decision, it can help me prepare for the future.

I typically order both tissue-based next-generation sequencing [NGS] and liquid-based [testing]. Tissue-based [testing] is always more sensitive. The problem with BTC is that many of our patients run into challenges [in terms of] having enough tissue to run NGS, especially for [patients with] hilar cholangiocarcinoma. Therefore, liquid biopsy can be very convenient to help us get those same data, but it’s not as sensitive as the tissue-based [testing], so I tend to [order] both. The other positive with liquid-based assays is that the turnaround time can be quicker.

What is your experience using the TOPAZ-1 and KEYNOTE-966 treatment protocols in practice?

I have more experience using the TOPAZ-1 study [regimen] because it’s been around longer. The data are very similar, and I consider them to be comparable. There are some differences in the study designs, the main one being [how] the chemotherapy backbone [was administered].

In the TOPAZ-1 study the gemcitabine and cisplatin chemotherapy backbone was continued for a total of 8 cycles and then completely stopped. Then durvalumab [was administered] continuously as monotherapy for maintenance. In KEYNOTE-966 gemcitabine/cisplatin was continued for 8 cycles. After that physicians had a choice of continuing single-agent gemcitabine in addition to pembrolizumab as maintenance therapy.

I tend to continue the immunotherapy as monotherapy [in the maintenance setting]. But there are some patients, for instance young patients [and] patients who can tolerate chemotherapy very well without any adverse effects, [such as] cytopenia, [for whom] I may consider continuing single-agent gemcitabine beyond 8 cycles. But both of [the studies] are positive and clearly establish the role of adding a checkpoint inhibitor to first-line gemcitabine/cisplatin therapy.

What does the future hold for HER2-targeted therapies in BTC?

The HER2-targeted therapy space has become very exciting. We’ve seen positive phase 2 trial data for trastuzumab [Herceptin] plus pertuzumab [Perjeta], fam-trastuzumab deruxtecan-nxki [Enhertu], trastuzumab plus tucatinib [Tukysa], and many other [regimens].

The only one of those that’s approved is trastuzumab deruxtecan, which is a tumor agnostic approval for any tumors that have HER2 immunohistochemistry 3+. That said several others, including trastuzumab/pertuzumab and also trastuzumab plus tucatinib, are currently listed in the National Comprehensive Cancer Network guidelines based on phase 2 data. It’s become a very challenging landscape for our physicians [in terms of] thinking about which [regimen] to choose. We would like to see more data that help us understand how to sequence these available therapies, and perhaps use them in the first-line setting like in other diseases.


  1. FDA approves durvalumab for locally advanced or metastatic biliary tract cancer. FDA. September 2, 2022. Accessed June 25, 2024.
  2. FDA approves Merck’s Keytruda (pembrolizumab) plus gemcitabine and cisplatin as treatment for patients with locally advanced unresectable or metastatic biliary tract cancer. News release. Merck. November 1, 2023. Accessed June 25, 2024.
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