Rapid Trajectory of Clinical Research in Biliary Tract Cancers

March 2022, Vol 3, No 1
Milind M. Javle, MD
Hubert L. and Olive Stringer Professor
GI Medical Oncology
University of Texas MD Anderson
Cancer Center, Houston
Chair, NCI Task Force,
Hepatobiliary Cancers

Dear Friends,

The 2022 ASCO GI Cancers Symposium clearly highlighted the rapid trajectory of clinical research in biliary tract cancers. One of the most eagerly anticipated studies, TOPAZ-1, was presented by Do-Youn Oh, MD, PhD, from Seoul National University Hospital in South Korea. This phase 3 clinical trial enrolled 685 patients and investigated the addition of the PD-L1–directed agent durvalumab to gemcitabine and cisplatin chemotherapy backbone versus these chemotherapies alone. The results demonstrated a statistically significant improvement in overall survival (OS), overall response rate (ORR), and progression-free survival (PFS), without dose-limiting toxicities.

PD-L1 expression in this study did not correlate with response, and there appeared to be an advantage for Asian patients with the immunochemotherapy, although this study was not powered for patient distribution by geography. Nevertheless, this study represents a milestone in the treatment of biliary cancers by (finally) bringing immunotherapy to the forefront of therapy.

Along the same lines, Robin Kate Kelley, MD, from the University of California, San Francisco, reported the results of a phase 2 clinical trial with the immunotherapy pembrolizumab combined with granulocyte macrophage colony-stimulating factors for advanced chemorefractory biliary tract cancer. In this study, the ORR was 12%, and interestingly, a numerical superiority in OS and PFS was seen with the immunotherapy in viral-related cholangiocarcinoma (CCA) compared with nonviral CCA.

We continue to learn about molecular targeting in CCA, and 2 studies—one by Mitesh J. Borad, MD, from the Mayo Clinic in Phoenix, and one by Rachna T. Shroff, MD, from the University of Arizona Cancer Center—used innovative retrospective study designs to describe (1) the relative benefit of futibatinib from clinical trials versus chemotherapy, and (2) the natural history of FGFR-altered CCA in the real-world setting. These types of analyses are particularly informative for uncommon subtypes of rare cancers.

In another subset of molecular targets, Madhulika Eluri, MD, Fellow at M.D. Anderson Cancer Center, and Dr Kelley, provided interesting data regarding family history of liver cancer in patients with CCA and the frequency of DNA repair genetic alterations.

Dr Eluri reported a large series of 429 patients and >1000 controls, noting a disproportionately high incidence of primary liver cancer in first-degree relatives of patients with CCA. Dr Kelley reported a 4.6% incidence of germline mutations and a 13% incidence of somatic mutations in DNA-damage repair genes in 804 patients with biliary tract cancer, with the highest incidence (19%) seen in gallbladder cancer. These data certainly make the case for molecular testing, which includes germline profiling for this population, akin to pancreatic cancer.

Pemigatinib and infigratinib are both effective for the treatment of CCA associated with FGFR2 fusions, but the activity of these agents in patients with FGFR2 mutations remains low. The FIDES-1 study (presented by me) demonstrated that derazantinib resulted in clinical benefit, with a disease control rate of 74% and PFS of 7.3 months, with tolerable adverse effects.

Targeted therapies often affect a patient’s quality of life (QOL). Christina X. Chamberlain, PhD, and colleagues from Servier Pharmaceuticals, reported that QOL was maintained with ivosidenib in the ClarIDHy phase 3 clinical trial compared with placebo in the management of patients with CCA and IDH1 mutation.

Finally, although we are excited by novel therapeutics and innovative clinical trials, Jessica M. Keilson, MD, and colleagues from the Cholangiocarcinoma Foundation reported sobering results regarding patients’ financial toxicity associated with clinical trial participation and the cost of targeted therapies, a fact that should be considered when offering an investigational therapy to our patients.


Milind Javle, MD

Milind M. Javle, MD
Hubert L. and Olive Stringer Professor
Department of Gastrointestinal Medical Oncology
Division of Cancer Medicine
The University of Texas
M.D. Anderson Cancer Center
Houston, TX
NCI Task Force: Hepatobiliary Cancers

Related Items

ASCO GI Presentations Show Progress in BTC
By Milind M. Javle, MD
March 2024, Vol 5, No 1
Editor-in-Chief Milind M. Javle, MD, highlights takeaways from the ASCO GI 2024 symposium, emphasizing the latest developments in biliary tract cancer.
Annual CCA Summit Is Now a Key Scientific Meeting in BTCs
By Milind M. Javle, MD
December 2023, Vol 4, No 4
The 5th annual CCA Summit, held October 19-21, 2023, in Scottsdale, AZ, was a very successful meeting by all measures and has gradually become one of the key scientific meetings in biliary tract cancers.
Advances in the Management of Patients With Biliary Cancer
By Milind M. Javle, MD
September 2023, Vol 4, No 3
As we approach the fall season, it is wonderful to reflect on some of the amazing research presented this year, most recently at the ASCO 2023 annual meeting. One of the major highlights of ASCO this year included the results of HER2/neu-directed novel therapies in biliary cancer. Shubham Pant, MD, MBBS, from MD Anderson Cancer Center, presented the results of the HERIZON-1 clinical trial of the bispecific antibody zanidatamab in HER2/neu-expressing biliary cancers.
Annual CCF Conference Brings Together All Stakeholders
By Milind M. Javle, MD
June 2023, Vol 4, No 2
This issue of CCA News highlights the Cholangiocarcinoma Foundation (CCF) 10th Annual Conference held in April. This meeting was chaired by Dr Chiara Branconi, a Lord Kelvin Adam Smith Reader at the University of Glasgow and a medical oncologist with Beatson Cancer Centre; and Dr Laura Goff, medical director of the Vanderbilt-Ingram Cancer Center’s Hematology and Oncology Division.
Exciting New Abstracts from the ASCO GI Cancers Symposium
By Milind M. Javle, MD
March 2023, Vol 4, No 1
Dr Javle provides his perspective on important abstracts presented at the ASCO Gastrointestinal Cancers Symposium, held January 19-21, 2023, in San Francisco, CA.
Highlights from the Fourth Annual CCA Summit
By Milind M. Javle, MD
December 2022, Vol 3, No 4
We have recently concluded the 4th Annual CCA Summit, which was held on October 13-15, 2022, in Denver, Colorado.
New Standard of Care Emerging for Treatment of BTCs
By Milind M. Javle, MD
September 2022, Vol 3, No 3
On September 2, 2022, the US Food and Drug Administration approved durvalumab in combination with gemcitabine/cisplatin for advanced biliary tract cancers (BTCs) on the basis of the TOPAZ-1 study.
Hot Topics at ASCO-GI 2022
By Milind M. Javle, MD
Dr Milind Javle provides his perspectives on key presentations on cholangiocarcinoma and biliary tract cancer at the 2022 ASCO Gastrointestinal Cancers Symposium.
Cholangiocarcinoma Research Continues to Thrive
By Milind M. Javle, MD
December 2021, Vol 2, No 4
The Third CCA Summit was held on October 21-22, 2021 in New Orleans. For the majority of the cholangiocarcinoma (CCA) community, this was their first “live” meeting since the pandemic.

Subscribe Today!

To sign up for our newsletter or print publications, please enter your contact information below.

I'd like to receive: