Among patients with unresectable hepatocellular carcinoma, those treated with lenvatinib had delays in definitive and meaningful deterioration of fatigue, pain, and diarrhea compared against those treated with sorafenib, according to a study in the Lancet Gastroenterology & Hepatology.
The post-hoc analysis of secondary and exploratory endpoints from the REFLECT trial assessed the effects of lenvatinib compared with sorafenib on health-related quality of life. The multicenter, randomized, phase 3 REFLECT study compared the efficacy and safety of lenvatinib vs sorafenib as a first-line systemic treatment in patients with unresectable hepatocellular carcinoma (ClinicalTrials.gov Identifier: NCT01761266).
Eligible patients were aged 18 years or older with unresectable hepatocellular carcinoma and 1 or more measurable target lesion. Participants were randomly assigned 1:1 to receive oral lenvatinib (12 mg/day for bodyweight ≥60 kg or 8 mg/day for bodyweight <60 kg) or sorafenib (400 mg twice daily) in 28-day cycles. Patient-reported outcomes (PROs) were obtained at baseline, on day 1 of each subsequent cycle, and at the end of treatment.
A total of 954 patients were enrolled between March 14, 2013, and July 30, 2015; 478 patients received lenvatinib and 476 received sorafenib and were included in the intention-to-treat population. PRO analyses were conducted in the PRO population (n = 931 [n = 468 for lenvatinib; n = 463 for sorafenib]).
Participants’ demographic and health characteristics did not differ significantly between treatment groups in the PRO population, and 592 of 931 (64%) had an Eastern Cooperative Oncology Group performance status of 0 at baseline.
Compared with patients who received sorafenib, those who received lenvatinib had nominally statistically significant delays in definitive, meaningful deterioration of fatigue (hazard ratio [HR], 0.83; 95% CI, 0.69-0.99), pain (HR, 0.80; 95% CI, 0.66-0.96), and diarrhea (HR, 0.52; 95% CI, 0.42-0.65), according to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 scale.
No difference was observed in time to definitive deterioration on the global health status/quality of life score (HR, 0.89; 95% CI, 0.73-1.09). The hazard ratios for time to definitive deterioration favored responders for all scales, and the median time to definitive deterioration for responders exceeded those of nonresponders by 4.8 to 14.6 months.
Study limitations include the open-label design of REFLECT, which excluded patients with 50% or greater liver occupation or portal vein invasion at the main portal vein. Additionally, attrition throughout the study was high, and missing data were assumed to be missing at random.
“The evidence of [health related quality of life] benefits in clinically relevant domains support the use of lenvatinib compared with sorafenib to delay functional deterioration in advanced hepatocellular carcinoma,” stated the researchers.
Disclosures: This study was funded by Eisai and Merck Sharp & Dohme. Some of the study authors declared affiliations with pharmaceutical companies.
Vogel A, Qin S, Kudo M, et al. Lenvatinib versus sorafenib for first-line treatment of unresectable hepatocellular carcinoma: patient-reported outcomes from a randomised, open-label, non-inferiority, phase 3 trial. Lancet Gastroenterol Hepatol. Published online June 1, 2021. doi:10.1016/S2468