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Patients with biliary cancer who undergo molecular profiling appear to survive significantly longer when compared with those who do not.

“Biliary tract cancer (BTC) exhibits diverse genetic alterations. Identifying actionable mutations was associated with significantly higher survival,” says Aiwu Ruth He, MD, PhD. Dr. He and colleagues reported study findings in a poster presentation at the 2024 ASCO Gastrointestinal Cancers Symposium.

Using next-generation sequencing, researchers can identify recurrent genomic alterations in BTC. Dr. He and colleagues analyzed the impact of molecular tests of BTC on the outcome of patients who receive systemic therapy for biliary cancer in real-life clinical settings. They conducted a retrospective analysis of data from patients with biopsy-proven BTC who received continued care at one comprehensive cancer center from 2018 through 2022. Patients with pancreatic cancer or primary hepatocellular carcinoma were excluded.

The 147 patients included in the final analysis had a mean age of 63 and 54% were female. The most common cancers among them were intrahepatic cholangiocarcinoma (77.5%), extrahepatic cholangiocarcinoma (15.6%), and gallbladder carcinoma (6.9%). Overall, 116 (79%) patients had one prior line of therapy, 24 (16%) had two, 6 (4%) had three, and 1 (1%) had one prior line of therapy. Tissue biopsy was performed in 59 (40%) of cases and blood biopsy in 6 (4%).

Molecular profiling was performed in 49.4% of patients and actionable mutations for FDA-approved treatments or clinical trial enrollment were found in 26.3%. Actionable mutations included KRAS (n=11), FGFR2 (n=9), IDH-1 (n=8), Her-2neu (n=5), BRCA1/2 (n=5), and PD-L1 (n=4; Figure).

Patients who underwent molecular profiling survived significantly longer (43±5 months vs. 25±4; P=0.013), and patients with actionable mutations survived even longer than the rest of the cohort (52±8 months vs. 26±7 months; P=0.019).

Molecular Profiling of Biliary Tract Cancer Is Important & Challenging

“It is important to obtain a molecular profile of the tumor for all patients with cholangiocarcinoma who will receive systemic therapy for biliary tract cancer,” Dr. He says. “There is an urgent need to overcome the challenge that many patients do not have enough tumor tissue for a molecular profile… While we focus on how some genetic alterations predict the response to therapeutics, we would like to understand whether some genetic alterations are prognostic for better survival. Is there benefit to combining treatments targeting multiple genetic alterations?”

“We expect to see the availability of more therapeutic agents that target specific genetic alterations,” she adds. “Clinicians should keep a lookout for new progress in precision medicine for biliary tract cancer and should encourage their patients to enroll in clinical trials.”