KRAS-mutant biliary tract cancer predicts shorter PFS on durvalumab + Gem/Cis

Gemcitabine/cisplatin plus durvalumab (GCD; PD-L1 blockade) was evaluated retrospectively in advanced biliary tract cancer patients treated front line at MSK with pretreatment tumor sequencing (n=236; 56% intrahepatic CCA, 23% gallbladder, 16% extrahepatic CCA; NCT01775072). With median follow-up 23 months, cohort median PFS was 9.1 months (95% CI 7.7–11.0) and 12- and 24-month OS rates were 68% and 45%; by contrast, TOPAZ-1 reported median PFS 7.2 months with durvalumab+Gem/Cis (vs 5.7 months with Gem/Cis alone) and a 24-month OS rate 23.6% (vs 11.5%). KRAS alterations (17%) were the clearest adverse biomarker: KRAS-altered vs KRAS-WT had median PFS 5.6 vs 11 months and median OS 11 vs 21 months, and KRAS remained independently associated with shorter PFS in multivariable analysis (HR 2.06, 95% CI 1.36–3.12; p<0.001), alongside liver metastases (HR 2.06; p<0.001), while higher baseline albumin was protective (HR 0.44 per 1-unit increase; p<0.001).