Mutations Matter: Cholangiocarcinoma Tumor Profiling Awareness

At least half of patients with cholangiocarcinoma have mutations in their tumors that may be treatable with targeted drugs or immunotherapies that are either experimental or approved for other cancer types. These are available through clinical trials.

Yet when surveyed, half of patients with this diagnosis said their tumor tissue hadn’t undergone molecular profiling to determine if those mutations were present. Why not? Most said they hadn’t known about this kind of testing.

The Cholangiocarcinoma Foundation ( — which supports and advocates for those with this rare cancer that affects the bile ducts — is determined to make sure everyone with the disease learns about and has access to genetic profiling and clinical trial partici­pation. The foundation is working toward that goal through its new program called Mutations Matter, funded with a $125,000 grant from Bayer Pharmaceuticals.

Through a new website (, educational videos and targeted email campaigns, the foundation plans to tell both patients and doctors why this testing should be done as soon as possible after a cholangiocarcinoma diagnosis.

“Profiling needs to be done immediately, so you can plan what you want to do next if it progresses,” Stacie Lindsey, president of the foundation, said in a presentation at the organization’s annual conference, held Jan. 30 in Salt Lake City, Utah. “Cholangiocarcinoma is the most highly targetable among gastrointestinal cancers,” she added — it expresses the most mutations that are potentially treatable with drugs already approved to treat other types of cancer.

The gap in knowledge on this topic lies mainly in the fact that 85 percent of patients with cholangiocarcinoma are treated outside major academic cancer centers, where both tumor profiling and access to clinical trials are standard, Lindsey said. In community treatment settings, she said, oncologists who treat cholangiocarcinoma tend to be generalists rather than gastrointestinal specialists, tumor profiling may be limited or discouraged, and access to clinical trials may be restricted or not offered.

When it comes to a rare cancer like cholangiocarcinoma, the fact that just 5 percent of adults with cancer participate in clinical trials is “tricky,” she said, because insufficient enrollment can lead to studies being canceled or pharma­ceutical companies and academia failing to invest in them.

The foundation conducted its survey of 132 patients and their profiling histories a year and a half ago, when the immunotherapy Keytruda (pembrolizumab) was approved for all solid tumors that are considered micro­satellite instability-high, meaning that they have trouble repairing their own DNA when it’s damaged. About 3 percent of patients with cholangiocarcinoma have that status and are eligible for the treatment, but they can’t know that unless their tumor tissue is profiled, Lindsey said.

Of the half of respondents who said that their tumors had been profiled, 62 percent noted that the test results had influenced their treatment decisions.

Lindsey cited 51-year-old survivor Matt Reidy as an example. He had his tumor profiled, and when Keytruda was approved two years later, it turned out he was eligible to take the drug.

“I started Keytruda, and within four months I had a complete response,” Reidy is quoted as saying on the Mutations Matter website. “I continued the therapy for 18 months total, and three years after starting, I remain cancer-free and consider myself cured.”

Lindsey said the foundation is running Mutations Matter with help from a variety of partners.

Komodo Health gathers data on where patients are being treated and how, to pinpoint where education is most needed. If hot spots are found at sites within the country, the foundation can wage email campaigns targeted to community oncologists there. Digital communications company DMD is in charge of those targeted email efforts, and public relations experts at EIN Communications created a communications plan and are reaching out to media.

It was D2 Creative that made the simple, digestible videos — called “illuminations” — that are available in six languages and aimed at patients and doctors. The Cholangiocarcinoma Foundation has established a blueprint for outreach to other nonprofit organizations that might benefit from sharing the videos with their members, Lindsey said.

Finally, Perthera Inc., a health care artificial intelligence company, is acting as a concierge for patients, facilitating genetic profiling for each and then generating a free report, including a list of potentially relevant clinical trials and how to contact them. Perthera is offering its services at no cost during the program’s first year, which began in June 2018.