Molecular determinants of outcome to gemcitabine, cisplatin, and nab-paclitaxel in patients with advanced biliary tract cancer

Summary

Clinicogenomic analysis (TruSight Oncology 500) of advanced biliary tract cancer treated with gemcitabine, cisplatin, and nab-paclitaxel (GAP; n=198) versus gemcitabine and cisplatin (GC; n=89). GAP modestly improved PFS (HR 0.764) without an OS difference overall. Frequent alterations spanned TP53, KRAS (16.4%), SMAD4, and TNFRSF14. Single-gene mutations did not predict benefit, but PI3K-pathway activation was associated with inferior PFS (HR 2.15) and OS (HR 2.10) on GAP — benefit from GAP was confined to patients without PI3K activation (Pinteraction=0.023 PFS, 0.003 OS), replicated in an independent validation cohort (GAP n=103, GC n=64).