WASHINGTON—A new treatment recently approved by the US Food and Drug Administration (FDA) for biliary tract cancer, or cholangiocarcinoma, offers a modest improvement in long-term survival rates. Yet even that is big news for patients with this rare and aggressive disease.

AstraZeneca’s durvalumab (Imfinzi®) is designed to be taken in combination with standard-of-care chemotherapy (gemcitabine plus cisplatin) by patients with locally advanced or metastatic cholangiocarcinoma.

The FDA based its September 5, 2022, approval on the TOPAZ-1 phase 3 clinical trial, which showed that 25% of patients treated with durvalumab plus chemotherapy were still alive 2 years later, compared to only 10% of those treated with chemotherapy alone. Similar results were seen in all prespecified subgroups in the trial, which involved 685 patients, regardless of tumor location. The median overall survival for those on durvalumab was 12.8 months, vs 11.5 months for those on chemotherapy alone.

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Durvalumab, a monoclonal antibody that is administered via intravenous infusion every 3 weeks, represents the first-ever immunotherapy for patients with cholangiocarcinoma. The Cholangiocarcinoma Foundation, a nonprofit group that advocates for the 23,000 or so Americans diagnosed with the condition each year, has enthusiastically welcomed its approval.

“This is an incremental step forward for patients,” Stacie Lindsey, the organization’s founder and CEO, said by phone from the charity’s headquarters in Salt Lake City, Utah. “It’s not like we’re going from 1 year of survival to 5 years. But what it does is open up an entire class of drugs that have not been available for these patients before.”

Stacie Lindsey, founder and CEO of the Cholangiocarcinoma Foundation (CCF). (Photo courtesy of CCF)

She added: “Cholangiocarcinoma has traditionally been considered a cold-tumor type, meaning it doesn’t respond to immunotherapy. This is the first trial that showed a positive response.”

Lindsey told Rare Disease Advisor that her organization is “very excited” about the FDA approval, despite the fact that durvalumab does not dramatically increase overall survival rates.

“Cancer patients are generally excited about immunotherapy options,” said Lindsey, who lost a brother to the disease in 2007. “In the last 2.5 years, the FDA has approved 5 drugs for this particular cancer. But 4 of those have been for targeted treatment options, for specific mutations. With this drug, hopefully every patient will benefit from it.”

Shubh Goel is vice president of US immuno-oncology and franchise head at AstraZeneca. What’s important about durvalumab, she said, is that 1 in 4 patients who took it along with receiving chemotherapy was still alive after 2 years, versus 1 in 10 who received chemotherapy alone.

“This is a special drug for us at AstraZeneca,” she said. “Clearly, there’s been an unmet medical need, and this marks our first foray into the liver cancer space. We believe the approval of Imfinzi represents a practice-changing advance for patients with biliary tract cancer who really need well tolerated and effective treatment options.”

Shubh Goel, AstraZeneca’s vice president and US franchise head for immuno-oncology. (Photo courtesy of AstraZeneca)

AstraZeneca got more good news on October 22, 2022, with FDA approval of the British company’s tremelimumab (Imjudo) in combination with durvalumab for unresectable hepatocellular carcinoma (HCC), the most common type of liver cancer.

Cholangiocarcinoma is one of the fastest-growing carcinomas in the United States, with the incidence of the disease at about 3 per 100,000 inhabitants. Doctors have also seen a drop in the age of onset. even as far more common cancers (such as lung cancer and melanoma) are declining in prevalence. Classically, cholangiocarcinoma was rarely diagnosed in patients younger than 60, but increasingly patients in their 50s, 40s, and even 30s have the disease.

Even so, cholangiocarcinoma is far more prevalent in Asia, where parts of Thailand see mortality rates as high as 85 per 100,000 because people who live there consume raw, pickled, fermented, or undercooked fish contaminated with a local parasite known as a liver fluke. About 10% of those infected with 2 species of this parasite will eventually develop cholangiocarcinoma.

One of the principal investigators on TOPAZ-1 trial was Aiwu Ruth He, associate professor of medicine at MedStar Georgetown University Hospital in Washington, DC, and a medical oncologist who specializes in cancers of the gastrointestinal tract.

“For cholangiocarcinoma, it’s always a challenge to carry a large randomized global study,” Dr. He said in an interview. “We’re excited about the data. In the field, a lot of therapies were tested, and we did not know if this would be positive or not. But this new combination made an incremental improvement in survival. We’re seeing the benefits, and in general, it’s quite well tolerated.”

Aiwu Ruth He, MD, PhD, an associate professor of medicine at MedStar Georgetown University Hospital in Washington, DC. (Photo courtesy of MedStar Georgetown)

Dr. He said the trial involved patients at sites in North and South America, Europe, and Asia.

AstraZeneca presented the results of the TOPAZ-1 trial at the 2022 American Society of Clinical Oncology Gastrointestinal Cancers Symposium. They were also published in the New England Journal of Medicine Evidence.

In July 2022, durvalumab plus chemotherapy was added to the National Comprehensive Cancer Network (NCCN) Guidelines as a Category 1 preferred regimen as first-line therapy for locally advanced or metastatic biliary tract cancer, based on the data from TOPAZ-1. The combination is also under review by regulatory agencies in Australia, Brazil, Britain, Canada, Israel, Japan, Singapore, Switzerland, and the European Union.