Growing up in Egypt as the daughter of 2 physics teachers, Reham Abdel-Wahab, MD, PhD, dreamed of working someday as a scientist.

Reham Abdel-Wahab, MD, PhD, chief scientific officer of the Cholangiocarcinoma Foundation (CCF). Credit: CCF

When she was 10, her father died of liver disease. That reinforced her determination to become a doctor, and also explains why she chose to focus on hepatocellular carcinoma—a decision that later enabled her to come to the United States and fulfill her dream.

Today, Dr. Abdel-Wahab is chief scientific officer of the Cholangiocarcinoma Foundation (CCF) as well as its director of research.

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Based in Houston, Texas, Dr. Abdel-Wahab did a 5-year research fellowship at MD Anderson Cancer Center and formerly chaired the foundation’s international research network, which now includes more than 200 members, half from the US and half from Asia.

Cholangiocarcinoma, a rare but particularly aggressive bile duct cancer, is one of the fastest-growing carcinomas in the United States, even as far more common cancers (such as lung cancer and melanoma) are declining in prevalence. Doctors diagnose at least 8000 new cases a year in the United States, where the incidence of the disease is about 3 per 100,000 inhabitants, Dr. Abdel-Wahab said.

At present, the 5-year survival rate for cholangiocarcinoma patients is about 9%, according to the foundation.

“Unfortunately, more than 70% of patients present at an advanced stage, like a stage 4, where the disease has expanded outside the liver,” Dr. Abdel-Wahab told Rare Disease Advisor in a recent interview. “With standard first-line gemcitabine/cisplatin therapy, we are speaking about less than one year, though definitely, with the new treatments that have been approved recently, there will be improvements in the survival rate.”

US doctors are also noting a drop in the age of onset of cholangiocarcinoma. Classically, it was rarely seen in patients younger than 60, but increasingly, patients in their 50s, 40s, and even 30s are being diagnosed with the disease—and no one’s sure why.

Learn more about the epidemiology of cholangiocarcinoma

The disease—considered resistant to chemotherapy—is far more prevalent in Asia, where parts of Thailand see mortality rates as high as 85 per 100,000 because inhabitants of those regions consume raw, pickled, fermented, or undercooked fish contaminated with a local parasite known as a liver fluke. About 10% of people infected with 2 species of this parasite will eventually develop cholangiocarcinoma.

A speaker from Swiss drug firm Basilea Pharmaceutica makes a presentation at the 2019 Annual Cholangiocarcinoma Foundation (CCF) Conference in Salt Lake City, Utah. Credit: CCF

“There’s also a lot of research correlating the association between cholangiocarcinoma and hepatitis, particularly hepatitis B and C, and also with metabolic syndrome—the triad of diabetes, hypertension, and obesity,” Dr. Abdel-Wahab said.

The CCF’s 9th annual conference took place February 23-25, 2022, in Salt Lake City, Utah, attracting 250 participants in person and another 900 online. Dr. Abdel-Wahab was among 56 speakers who presented basic, translational, and clinical research, including new data on an immunotherapy option for patients.

In addition, 40 poster presentations were featured at the conference, during which some 200 participants wearing glow-in-the-dark clothing joined in a “Light it Green for CCA” walk through downtown Salt Lake City while carrying green lanterns to symbolize hope for a cure. The sky bridge at City Creek Center was also illuminated in green, the official color of cholangiocarcinoma.

Cholangiocarcinoma Foundation (CCF) Founder and CEO Stacie Lindsey. Credit: CCF

CCF Founder and CEO Stacie Lindsey of Lehi, Utah, said that during the COVID-19 pandemic—which forced her organization to hold its last 2 annual conferences virtually—“we got a lot done.”

“We had 3 approvals for new therapies, and we’ve had the ability to energize patients and educate them about the opportunity for clinical trials,” said Lindsey, who created the CCF after her 39-year-old brother, Mark, died of cholangiocarcinoma in 2006.

At that time, there was no standard of care and only 4 clinical trials for cholangiocarcinoma. Today, she said, some 150 clinical trials for the disease are ongoing—with many more in the solid tumor area, for which cholangiocarcinoma patients might qualify.

“If you want a shot at the newest, greatest opportunities, clinical trials will be a part of your treatment program, especially when you have such a low standard of care,” Lindsey said. “So we try to give patients as much information as we can. We feel like it’s our responsibility that they know all the options.”

In April 2020, the US Food and Drug Administration (FDA) approved Incyte’s pemigatinib (Pemazyre®), an oral kinase inhibitor, to treat adults with locally advanced or metastatic cholangiocarcinoma. The therapy is specifically for patients with a fibroblast growth factor receptor 2 (FGFR2) mutation, making it the first targeted therapy for patients with this disease.

Participants attend the annual Cholangiocarcinoma Foundation (CCF) conference in Salt Lake City, Utah. Credit: CCF

Then, on May 28, 2021, the FDA granted accelerated approval to QED Therapeutics’ infigratinib (Truseltiq®), a kinase inhibitor for adults with previously treated unresectable locally advanced or metastatic cholangiocarcinoma with FGFR2.

Less than 3 months later, on August 25, 2021, the FDA approved Servier Pharmaceuticals’ ivosidenib (Tibsovo®) for adults with previously treated, locally advanced, or metastatic cholangiocarcinoma with an isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.

Perhaps most encouraging are the results from AstraZeneca’s TOPAZ-1 study, a phase 3 trial which showed that durvalumab (Imfinzi®) combined with standard-of-care chemotherapy led to improved overall survival in patients with cholangiocarcinoma, vs placebo plus chemotherapy. The immunotherapy is FDA-approved for the treatment of 2 types of lung cancer.

“The TOPAZ trial data is one of the first immunotherapy trials to show a positive response in cholangiocarcinoma, which has usually been classified as a cold tumor,” Lindsey said of the double-blind trial, which included 685 patients in 18 countries—55% of them in Asia. “The results mark a step forward and quite possibly a significant change in how clinical trials move forward if the FDA approves this treatment.”