Safety and efficacy of lenvatinib by starting dose (8 mg or 12 mg) based on body weight in patients with unresectable hepatocellular carcinoma in REFLECT.

316 Background: Lenvatinib (LEN) demonstrated statistical confirmation of noninferiority versus sorafenib (SOR) for overall survival (OS), and improved progression-free survival (PFS), time to progression, and objective response rate (ORR) in pts with uHCC in REFLECT (Kudo M et al, Lancet 2018). We report the efficacy and safety of LEN by starting dose, which was based on body weight (BW). Methods: In REFLECT, a multicenter, open-label, noninferiority trial, pts with uHCC were randomized 1:1 to LEN (BW < 60 kg: 8 mg/d; BW ≥ 60 kg: 12 mg/d; QD) or SOR (400 mg BID). Efficacy was analyzed by intention-to-treat; safety was analyzed in pts who received treatment, in each dose group. Results: Of 478 pts randomized to LEN, 151 (male, 70%; median age, 65 y) and 327 (male, 91%; median age, 62 y) were included in the LEN starting dose groups of 8 mg/d or 12 mg/d, respectively. In the 8-mg group, 14% of pts were from Western regions; 86% from Asia-Pacific. In the 12-mg group, 42% were from Western regions; 58% from Asia-Pacific. Median OS was 13.4 (95% CI: 10.5–15.7) and 13.7 months (95% CI: 12.0–15.6); ORR was 22.2% and 24.9% for pts with BW < 60 kg and ≥ 60 kg, respectively. Median PFS was 7.4 months in both groups. Median duration of treatment: 8-mg group, 5.6 months; 12-mg group, 6.3 months. Mean LEN relative dose intensity: 8-mg group, 87.7%; 12-mg group, 87.5%. Most common any-grade adverse events (AEs; 8-mg vs 12-mg) were hypertension (43% vs 42%), diarrhea (35% vs 40%), decreased appetite (33% vs 35%), weight loss (29% vs 32%), and fatigue (28% vs 31%). Adjusted by treatment duration, AE rates (episodes/patient-year) were similar for 8-mg versus 12-mg: hypertension (0.79 vs 0.78), diarrhea (1.06 vs 0.99), decreased appetite (0.63 vs 0.59), weight loss (0.50 vs 0.51), and fatigue (0.52 vs 0.47). Pharmacokinetic profiles were similar between groups. Conclusions: LEN efficacy was comparable between groups. Exposure to LEN was greater for the 12-mg versus 8-mg group. When AEs were adjusted by treatment duration, no notable differences in the AE profiles between the starting doses were observed. Altogether, these results support the 8-mg and 12-mg starting doses based on BW of < 60 kg and ≥ 60 kg, respectively, in REFLECT. Clinical trial information: NCT01761266.