Cholangiocarcinoma News

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

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