Evaluating Patient Outcomes Following Liquid Biopsy in Advanced Cholangiocarcinoma

Patients with advanced cholangiocarcinoma (CCA) often experience failure rates of up to 27% when undergoing tissue biopsies. Many physicians are turning to liquid biopsies to identify actionable molecular alterations in these patients.

A new study led by Amit Mahipal, MPH, MBBS, and presented at the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium investigated the rate of molecular alteration detection using circulating tumor DNA (ctDNA) testing. The study also evaluated common treatment patterns in advanced CCA and outcomes for those who received ivosidenib following ctDNA-detected IDH1 mutations.

A guideline-recommended biomarker was identified in 18% of the 1495 patients diagnosed with more than 1 ctDNA alteration. Of those with intrahepatic CCA (n=403), 11% were determined to have had an IDH1 mutation, and 9% had an FGFR2 fusion. One percent were diagnosed with high microsatellite instability, 1% had a BRAF V600E mutation, less than 1% had ERBB2 amplification, and less than 1% had RET fusion.

Of the participating patients, gemcitabine and cisplatin (48%) were the most common first-line therapies, while FOLFOX (21%), gemcitabine and cisplatin (13%), and capecitabine (11%) were the most common second-line therapies.

Researchers noted that patients with IDH1 mutations who received ivosidenib (n=21) demonstrated improved real-world time-to-treatment discontinuation (rwTTD; 4.6 vs 2.8, respectively; P=.1011) and real-world time to next treatment (rwTTNT; 11.0 vs 5.2, respectively; P=.2559) when compared with those receiving chemotherapy (n=33).

No difference in real-world overall survival between those who received ivosidenib and those who did not was detected.

Investigators concluded that ctDNA detects the rate of actionable molecular alterations at a comparable rate (18%) to tissue-based testing. They also noted that patients with ctDNA-detected IDH1 mutations who were treated with ivosidenib demonstrated some improvement in rwTTD and rwTTNT but not enough to be statistically significant.

“These data support the clinical utility of liquid biopsy to identify advanced CCA patients who may benefit from targeted therapy,” the researchers wrote.