Safety and efficacy of 12 mg/d lenvatinib (LEN) in patients with unresectable hepatocellular carcinoma (uHCC) and bodyweight >80 kg in REFLECT
Session type: Poster / e-Poster / Silent Theatre session
In a phase 3 trial (REFLECT), LEN (a multikinase inhibitor of VEGFR 1-3, FGFR 1-4, PDGFRα, RET, and KIT) demonstrated a treatment effect on overall survival by statistical confirmation of noninferiority vs sorafenib for first-line treatment of uHCC. Dosing by bodyweight in REFLECT was based on a phase 2 study of LEN in uHCC and PK modelling. Cutoff values were LEN 8 mg/d for bodyweight <60 kg and 12 mg/d for bodyweight ≥60 kg. This post hoc analysis of REFLECT assessed safety and efficacy of LEN in patients with bodyweight >80 kg.
Patients were stratified by baseline bodyweight: <60 kg, ≥60 to ≤80kg, and >80 kg. Safety and efficacy outcomes by bodyweight group were assessed.
Baseline demographics among groups were generally similar. Median treatment durations (months) were similar (range, 5.59-6.54), as were mean LEN relative dose intensities (range, 86%-93%). Key safety and efficacy data are reported (Table). Adjusted by treatment duration, adverse-event rates (episodes/patient-year) were similar across bodyweight groups. No adjustments were made for comorbidities by bodyweight groups.
Table: Efficacy and AEs of Interest by bodyweight
Bodyweight <60 kg (n=153)
Bodyweight ≥60 to ≤80 kg (n=234)
Bodyweight >80 kg (n=89)
Median OS, months
Median PFS, months
ORR (mRECIST by investigator), %
Hypertension, n (%)
Palmar-plantar erythrodysesthesia, n (%)
Proteinuria, n (%)
Diarrhea, n (%)
In this post hoc analysis including patients of bodyweight >80 kg receiving LEN 12 mg/d, efficacy and safety were similar to results in REFLECT. These results are consistent with the approved dose of 8 mg/d (bodyweight <60 kg) and 12 mg/d (bodyweight ≥60 kg) of LEN in uHCC.