Dr Bekaii-Saab on Evolving Sequencing Approaches in CRC

nable alterations include the KRAS G12C mutation, for which the KRAS G12C inhibitor adagrasib (Krazati) has been incorporated into National Comprehensive Cancer Network guidelines, according to Bekaii-Saab. BRAF V600E mutations, found in approximately 5% to 10% of biliary tract cancers, are responsive to combined BRAF/MEK inhibition using agents like dabrafenib (Tafinlar) plus trametinib (Mekinist), he noted. IDH1 mutations, present in approximately 20% of intrahepatic cholangiocarcinomas, can be targeted with ivosidenib (Tibsovo), which has demonstrated progression-free survival benefit and a modest overall survival advantage, although ORRs have been limited, he stated.

Furthermore, an expanding list of rare oncogenic fusions is being identified and matched with corresponding targeted therapies, contributing to the growing paradigm of precision oncology in biliary tract cancers, Bekaii-Saab emphasized. Overall, despite the relative rarity of biliary tract malignancies, approximately 30% to 40% of patients may benefit from biomarker-driven therapies beyond conventional chemotherapy and immunotherapy, many of which elicit ORRs in the 30% to 40% range, with the notable exception of ivosidenib, he concluded.