Cholangiocarcinoma Awareness: Immunotherapy, Precision Medicine, and the Importance of Molecular Testing With Kannan Thanikachalam, MD
Expert Perspectives · Lyn Brook · 2026-02-23
Cholangiocarcinoma has historically been a challenging malignancy to treat, marked by limited therapeutic options and poor outcomes. In this interview honoring Cholangiocarcinoma Awareness Month, Kannan Thanikachalam, MD, a Gastrointestinal Medical Oncologist at Roswell Park Comprehensive Cancer Center, discusses how the treatment landscape has evolved in recent years and highlights the growing roles of immunotherapy, molecular profiling, and clinical trial participation in improving patient care.
A Rapidly Changing Treatment Landscape
According to Dr. Thanikachalam, the most meaningful advances in cholangiocarcinoma management have occurred within the past five to six years. “In the early 2000s, there was no standard of care for treatment of cholangiocarcinoma,” he explained. The first major breakthrough came in 2008, when gemcitabine and cisplatin emerged as the standard chemotherapy backbone.
However, progress stalled for more than a decade. “There were no major updates from 2008 until 2020/2021,” Dr. Thanikachalam said, when pivotal trials reshaped first‑line treatment. The TOPAZ‑1 and KEYNOTE studies demonstrated improved outcomes with the addition of immunotherapy to chemotherapy, establishing a new standard that combines gemcitabine and cisplatin with either durvalumab or pembrolizumab.
These advances marked a turning point, signaling that immunotherapy could play a meaningful role in cholangiocarcinoma treatment—a disease long considered refractory to novel systemic approaches.
Current Standards of Care and Individualized Treatment
Dr. Thanikachalam emphasized that staging remains the first and most critical step in determining treatment strategy. For patients with disease beyond early‑stage, potentially resectable cholangiocarcinoma, combination therapy is now the norm. “The current standard of care is a combination of chemotherapy and immunotherapy together with gemcitabine cisplatin along with durvalumab or pembrolizumab, depending on patient preference and physician preference,” he said.
Beyond first‑line therapy, treatment decisions increasingly rely on molecular profiling. Cholangiocarcinoma is now recognized as a genetically heterogeneous disease, with actionable alterations varying by tumor location. Dr. Thanikachalam explained that intrahepatic and extrahepatic cholangiocarcinomas harbor distinct molecular features.
“In intrahepatic cholangiocarcinoma, we see a lot more mutations like IDH1 and FGFR2 fusions,” he noted. In contrast, extrahepatic tumors more commonly demonstrate “HER2 amplification or overexpression,” along with occasional BRCA or BRAF mutations. Many of these alterations can be targeted with oral or other non‑chemotherapy agents, expanding options in the second‑line and later settings.
This molecularly-driven approach represents one of the most transformative developments in the field. “The space has significantly changed and evolved within the last six years,” Dr. Thanikachalam said, adding that ongoing clinical trials continue to explore new targeted strategies.
The Critical Role of Comprehensive Molecular Testing
One lesser‑known but highly impactful aspect of cholangiocarcinoma care is the prevalence of actionable genomic alterations. Dr. Thanikachalam estimates that “around 30% to 40% of cholangiocarcinoma” cases harbor DNA changes that can be treated with non‑chemotherapy options.
For this reason, he stressed the importance of comprehensive next‑generation sequencing (NGS) for all patients with advanced disease. Smaller or limited testing panels may miss clinically relevant alterations, potentially depriving patients of effective targeted therapies or clinical trial opportunities.
Multidisciplinary Care and Quality of Life
Cholangiocarcinoma often presents unique supportive care challenges, making a multidisciplinary approach essential. Dr. Thanikachalam highlighted common complications such as cholangitis, biliary obstruction, and jaundice, which can significantly affect quality of life during treatment.
“It’s very important to maintain the quality of life as well, as they go through the treatment,” he said, pointing to the importance of timely biliary stenting and coordinated inpatient and outpatient care. Nursing, interventional endoscopy, nutrition support, and symptom management all play key roles in optimizing outcomes.
Looking ahead, Dr. Thanikachalam emphasized that meaningful progress will depend heavily on clinical trial participation. Cholangiocarcinoma is classified as a rare cancer, with approximately 8,000 to 10,000 new cases annually in the United States.
Raising Awareness and Supporting Patients
Finally, Dr. Thanikachalam encouraged patients and clinicians alike to engage with advocacy organizations and educational opportunities. He highlighted the Cholangiocarcinoma Foundation as a vital patient‑centered resource and recommended attendance at the annual Cholangiocarcinoma Conference in Salt Lake City, which brings together patients, families, and multidisciplinary experts. Such forums provide education, community support, and access to leading specialists in medical, surgical, and radiation oncology.
Key Takeaways
Cholangiocarcinoma treatment has evolved rapidly over the past 5 to 6 years, with immunotherapy now part of first‑line care.
Gemcitabine/cisplatin plus durvalumab or pembrolizumab is the current standard for advanced disease.
Molecular profiling is essential: “Around 30% to 40%” of cases harbor actionable DNA alterations.
Tumor location matters, with distinct molecular patterns in intrahepatic versus extrahepatic disease.
Comprehensive NGS testing should be standard for advanced cholangiocarcinoma.
Multidisciplinary care and clinical trial participation are critical to improving outcomes in this rare cancer.
About Dr. Thanikachalam
Kannan Thanikachalam, MD, is a Gastrointestinal Medical Oncologist at Roswell Park Comprehensive Cancer Center, where he specializes in the treatment of hepatobiliary and upper GI cancers. He provides expert care in both inpatient and outpatient settings, with a particular focus on advancing the management of rare tumors like cholangiocarcinoma through immunotherapy and targeted clinical trials.