New Standard of Care Emerging for Treatment of BTCs

September 2022, Vol 3, No 3
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

Dear Readers,

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. This is an important milestone and the fourth drug to be approved for this cancer within 2 years—a truly remarkable achievement. Additional data from this important study were presented at ASCO 2022 and the recently concluded ESMO 2022. Durvalumab has been beneficial for diverse patient populations: Okusaka and team demonstrated its effectiveness in both initially unresectable and recurrent disease at the ESMO 2022 meeting. Burris and colleagues had earlier reported at ASCO 2022 that the addition of durvalumab to chemotherapy did not deteriorate quality of life, and the survival improvement occurred across a diverse population, although there appears to be a greater benefit in Asian patients. Similarly, the effectiveness of durvalumab may extend across the 3 BTC types. After a decade, we now have a new standard of care, and we welcome the advent of immunotherapy to BTC! Other agents being explored include toripalimab, sintilimab, and durvalumab plus tremelimumab, and it is hoped that these agents will improve on the results seen in the TOPAZ-1 analyses.

Another area of active development is the HER2/neu pathway in BTC. The HERIZON-BTC-01 trial of zanidatamab for patients with HER2-expressing BTC has completed accrual expeditiously, and we anxiously await its results. Trastuzumab deruxtecan, the antibody–drug conjugate, appears to be effective, irrespective of the degree of HER2 expression in a variety of solid tumors, including breast, colorectal, and biliary. Ohba and colleagues noted a 36.4% overall response rate in HER2 amplified or expressers. Interstitial lung disease is a notable complication and is dose/duration-related. Tucatinib plus trastuzumab is an exciting new combination in this space with positive results in colorectal cancer. The same combination will be explored in BTCs in a basket study. Overall, we look forward to a deeper understanding of the HER2 pathway in BTCs and access to these novel agents in the clinic.

FGFR genetic aberrations continue to be studied. The FIGHT-202 updated data continue to reflect the benefit of pemigatinib in FGFR2-fusion cholangiocarcinoma (CCA). The PROOF 301 trial is investigating the role of infigratinib as a first-line treatment for this cancer. Futibatinib has promising activity as a covalent inhibitor and results in durable responses with limited toxicity. Agents under investigation for FGFR-inhibitor resistance include tinengotinib (TT-00420) and RLY4008, and promising preliminary results were presented at ASCO 2022 and ESMO 2022.

In this issue of CCA News, Dr Flavio Rocha provides insightful commentary on the role of perioperative therapy for CCA. The NEO-GAP study, led by Dr Shishir Maithel, has clearly indicated the feasibility of multiagent chemotherapy in the neoadjuvant setting followed by surgery. The optimal postoperative adjuvant therapy continues to be debated. BILCAP has clearly established capecitabine as a standard, and the STAMP study from Korea suggested that gemcitabine/cisplatin does not improve on the results achieved with capecitabine in the adjuvant setting. Finally, although we have made great strides in targeted strategies for BTCs, Upadhyay and colleagues have noted that a substantial fraction of patients die from liver failure, thereby highlighting the case for liver-directed therapy in this cancer.


Milind M. Javle, MD

Related Items

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.
Rapid Trajectory of Clinical Research in Biliary Tract Cancers
By Milind M. Javle, MD
March 2022, Vol 3, No 1
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.
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: