HER2 Is a Viable Target in Biliary Tract Cancer

There is increasing evidence supporting routine performance of next-generation sequencing to identify targetable genomic abnormalities in biliary cancers. Regulatory approval has recently been achieved for agents targeting the fibroblast growth factor receptor (FGFR) and isocitrate dehydrogenase 1 (IDH-1) pathways.

Investigators now report results from a cohort of patients with HER2-positive advanced biliary cancers in MyPathway, an open-label, phase 2, basket trial of patients with advanced solid tumors and potentially targetable molecular alterations. Patients with previously treated advanced biliary cancer who tested positive for HER2 based on immunohistochemistry, fluorescent in situ hybridization testing, or next-generation sequencing and had no prior HER2-targeted therapy were treated with pertuzumab combined with trastuzumab on an every-3-week schedule.

Of 39 patients, 41% had received one prior regimen and 44% had received two or more, 41% had gallbladder primaries and 36% had intra- or extrahepatic primaries, and 80% were identified as HER2-positive by gene amplification.

Response rate — the primary endpoint — was 23%, and another 28% had stable disease. The median duration of response was 10.8 months. Median progression-free survival was 4.0 months and overall survival was 10.9 months. Grade 3 or higher treatment-related adverse events were uncommon (8%).