CCF Welcomes a New Standard of Care

Recognizing a major step forward for improved patient outcomes, the Cholangiocarcinoma Foundation (CCF; https://cholangiocarcinoma.org/) welcomed a new standard of care for the New Year. With the US Food and Drug Administration approval of AstraZeneca’s Imfinzi (durvalumab), patients with cholangiocarcinoma (CCA) now have an immunotherapy option for first-line treatment.¹ The phase 3 TOPAZ-1 trial showed that durvalumab in combination with standard-of-care chemotherapy resulted in improved overall survival versus placebo plus chemotherapy in patients with advanced biliary tract cancer (BTC).²

This is the first time an immunotherapy drug has been shown as effective for this disease. It is hoped that this milestone approval will open doors for other innovative immunotherapy combinations. CCF has partnered with AstraZeneca and other companies seeking to develop more effective treatments for CCA to provide patient input on clinical trial design and encourage enrollment in the pivotal studies needed to develop evidence of safety and efficacy for new therapies.

BTCs include intrahepatic and extrahepatic CCA and gallbladder cancer, each having different genetic influences, risk factors, and clinical presentations. CCA is a cancer that forms in the bile ducts of the liver. Each year, approximately 10,000 people in the United States are diagnosed with CCA, and it is the second most common primary liver cancer in the world.³

Overall, patients with BTC have a poor prognosis, and only 5% to 15% survive 5 years.⁴ This dismal outlook has fueled the urgency for the development of novel therapies and underscores the tremendous enthusiasm and hope engendered in the CCA community by news of a new, more effective standard of care.

“As a 12-year survivor of stage IV intrahepatic CCA, I am excited to see a new standard of care for patients with CCA, and this is the first improvement since 2010. I hope we continue to see additional treatment options for our patient community that provide more hope for those in need,” said Melinda Bachini, CCF director of advocacy.

Durvalumab is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumor’s immune-evading tactics and releasing the inhibition of immune responses. AstraZeneca provided confirmatory evidence from its clinical trial that 35.1% of those taking durvalumab with the chemotherapy combination were still alive at 12 months, compared with 25.6% taking just the chemotherapy.² At 24 months, survival was 24.9% and 10.4%, respectively.²

“The durvalumab approval is a big step forward and a significant change in trajectory for the treatment options available to this community. A new first-line treatment opens doors and increases opportunities for patients. We are grateful to all who participated in this clinical trial,” said Stacie Lindsey, CCF founder and CEO.

TOPAZ-1 lead study author Do-Youn Oh, MD, PhD, a professor in the Division of Medical Oncology of the Department of Internal Medicine at Seoul National University Hospital and Seoul National University College of Medicine in Seoul, South Korea, explained in a news release that patients were enrolled in the study from 105 centers across 17 countries including the United States.⁵ More than half of the patients were enrolled from centers in Asian countries. Notably, 55% of patients had intrahepatic cancers, 19% had extrahepatic cancers, and 25% had gallbladder cancer.⁵ The double-blind study randomized 685 patients with previously untreated, unresectable locally advanced, recurrent, or metastatic BTC 1:1 to receive 1500 mg of durvalumab every 3 weeks versus placebo plus 1000 mg/m² of gemcitabine and 25 mg/m² of cisplatin on days 1 and 8 every 3 weeks.⁵

Patients were treated for up to 8 cycles, which was followed by 1500 mg of durvalumab or placebo every 4 weeks until disease progression or unacceptable toxicity. The researchers demonstrated a 20% reduction in the risk of death with durvalumab plus chemotherapy versus placebo plus chemotherapy.⁵

“We’re proud to have worked hand in hand with CCF and the broader BTC community to bring a new treatment to patients who have seen little progress in the first-line treatment landscape in years,” said Shubh Goel, US immuno-oncology franchise head at AstraZeneca. “As the first immunotherapy in this setting, this approval underscores our commitment to transforming cancer care and bringing hope to those living with rare and difficult-to-treat cancers like BTCs.”

CCF hopes this approval energizes clinicians, researchers, industry sponsors, regulators, and advocates across the rare-cancer community to stay focused on development of better treatment options for difficult-to-treat cancers. We are more hopeful than ever about the many exciting options moving through the drug development pipeline in clinical trials, with an eye toward a cure or cures for CCA.

References

1. US Food and Drug Administration. FDA approves durvalumab for locally advanced or metastatic biliary tract cancer. www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-locally-advanced-or-metastatic-biliary-tract-cancer. Accessed January 15, 2023.
2. Oh DY, He AR, Qin S, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. NEJM Evidence. 2022;1(8).
3. Blechacz B. Cholangiocarcinoma: current knowledge and new developments. Gut Liver. 2017;11(1):13-26.
4. AstraZeneca. Imfinzi plus chemotherapy significantly improved overall survival in 1st-line advanced biliary tract cancer in TOPAZ-1 phase III trial at interim analysis. https://www.astrazeneca.com/media-centre/press-releases/2021/imfinzi-improved-survival-in-biliary-tract-cancer.html. Accessed January 15, 2023.
5. OncLive. Durvalumab plus chemotherapy improves survival in advanced biliary tract cancer. https://www.onclive.com/view/durvalumab-plus-chemotherapy-improves-survival-in-advanced-biliary-tract-cancer?s=03. Accessed January 20, 2023.