REFLECT

REFLECT, trial NCT01761266 sponsored by Eisai and reported in 2018, showed that lenvatinib matched sorafenib on survival with more tumour shrinkage, giving first-line unresectable hepatocellular carcinoma a second option after a decade. It randomised 954 patients in a non-inferiority design, met its primary overall survival endpoint for non-inferiority, and improved progression-free survival and response rate by modified RECIST, making it the first positive first-line trial since SHARP. OnCo links it to hepatocellular carcinoma, lenvatinib, sorafenib, Ann-Lii Cheng and Masatoshi Kudo. Because it showed equivalence rather than superiority, whether lenvatinib's higher response rate matters clinically, particularly before local therapies, remains the open question.