Safety and efficacy of 12 mg/d lenvatinib (LEN) in patients with unresectable hepatocellular carcinoma (uHCC) and bodyweight >80 kg in REFLECT


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Arndt Vogel1,Masatoshi Kudo2,Ann-Lii Cheng3,Max W. Sung4,Richard S. Finn5,Albert Y. Lin6,Ghassan K. Abou-Alfa7,Angel Alsina8,Valeriy Breder9,Niall Tebbutt10,Pia Osterlund11,C. J. Yen12,Min Ren13,Soamnauth Misir13,Corina E. Dutcus13,Daniel Palmer14,Philippe Merle15,Matthias Pinter16,TR Jeffry Evans17
1Hannover Medical School,2Kindai University School of Medicine,3National Taiwan University Hospital,4Tisch Cancer Institute at Mount Sinai,5Geffen School of Medicine, UCLA Medical Center,6VA Palo Alto Health Care System,7Memorial Sloan Kettering Cancer Center,8Tampa General Hospital,9N.N. Blokhin Russian Cancer Research Center, Ministry of Health of the Russian Federation,10Olivia Newton-John Cancer Centre,11Tampere University and Central Hospital,12National Cheng Kung University Hospital,13Eisai Inc.,14University of Liverpool, Liverpool,15CHU de Lyon -Hospital La Croix-Rousse,16Medical University of Vienna,17University of Glasgow

Abstract

Background

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.

Method

Patients were stratified by baseline bodyweight: <60 kg, ≥60 to ≤80kg, and >80 kg. Safety and efficacy outcomes by bodyweight group were assessed.

Results

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

Parameter

Bodyweight <60 kg (n=153)

Bodyweight ≥60 to ≤80 kg (n=234)

Bodyweight >80 kg (n=89)

Median OS, months

13.4

13.6

14.9

Median PFS, months

7.4

7.3

9.2

ORR (mRECIST by investigator), %

22

24

28

Hypertension, n (%)

66 (43)

97 (42)

38 (43)

Palmar-plantar erythrodysesthesia, n (%)

37 (24)

65 (28)

26 (29)

Proteinuria, n (%)

38 (25)

59 (25)

20 (23)

Diarrhea, n (%)

54 (35)

91 (39)

39 (44)

Conclusion

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.