REFLECT-a phase 3 trial comparing efficacy and safety of lenvatinib to sorafenib for the treatment of unresectable hepatocellular carcinoma: an analysis of Japanese subset.
Adult
Aged
Aged, 80 and over
Antineoplastic Agents
/ therapeutic use
Carcinoma, Hepatocellular
/ drug therapy
Female
Humans
Intention to Treat Analysis
Japan
Liver Neoplasms
/ drug therapy
Male
Middle Aged
Phenylurea Compounds
/ therapeutic use
Quinolines
/ therapeutic use
Sorafenib
/ therapeutic use
Survival Analysis
Treatment Outcome
Hepatocellular carcinoma
Japanese population
Lenvatinib
REFLECT trial
Sorafenib
Journal
Journal of gastroenterology
ISSN: 1435-5922
Titre abrégé: J Gastroenterol
Pays: Japan
ID NLM: 9430794
Informations de publication
Date de publication:
Jan 2020
Jan 2020
Historique:
received:
12
04
2019
accepted:
27
10
2019
pubmed:
14
11
2019
medline:
29
4
2021
entrez:
14
11
2019
Statut:
ppublish
Résumé
A phase 3, multinational, randomized, non-inferiority trial (REFLECT) compared the efficacy and safety of lenvatinib (LEN) and sorafenib (SOR) in patients with unresectable hepatocellular carcinoma (uHCC). LEN had an effect on overall survival (OS) compared to SOR, statistically confirmed by non-inferiority [OS: median = 13.6 months vs. 12.3 months; hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.79-1.06], and demonstrated statistically significant improvements in progression-free survival (PFS) and the objective response rate (ORR) in the overall population. The results of a subset analysis that evaluated the efficacy and safety of LEN and SOR in the Japanese population are reported. The intent-to-treat population enrolled in Japan was analyzed. Of 954 patients in the overall population, 168 Japanese patients were assigned to the LEN arm (N = 81) or the SOR arm (N = 87). Median OS was 17.6 months for LEN vs. 17.8 months for SOR (HR 0.90; 95% CI 0.62-1.29). LEN showed statistically significant improvements over SOR in PFS (7.2 months vs. 4.6 months) and ORR (29.6% vs. 6.9%). The relative dose intensity of LEN and SOR in the Japanese population was lower than in the overall population. Frequently observed, related adverse events included palmar-plantar erythrodysaesthesia syndrome (PPES), hypertension, decreased appetite, and proteinuria in the LEN arm, and PPES, hypertension, diarrhea, and alopecia in the SOR arm. The efficacy and safety of LEN in the Japanese population were similar to those in the overall population of REFLECT. With manageable adverse events, LEN is a new treatment option for Japanese patients with uHCC. ClinicalTrials.gov. No. NCT01761266.
Sections du résumé
BACKGROUND
BACKGROUND
A phase 3, multinational, randomized, non-inferiority trial (REFLECT) compared the efficacy and safety of lenvatinib (LEN) and sorafenib (SOR) in patients with unresectable hepatocellular carcinoma (uHCC). LEN had an effect on overall survival (OS) compared to SOR, statistically confirmed by non-inferiority [OS: median = 13.6 months vs. 12.3 months; hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.79-1.06], and demonstrated statistically significant improvements in progression-free survival (PFS) and the objective response rate (ORR) in the overall population. The results of a subset analysis that evaluated the efficacy and safety of LEN and SOR in the Japanese population are reported.
METHODS
METHODS
The intent-to-treat population enrolled in Japan was analyzed.
RESULTS
RESULTS
Of 954 patients in the overall population, 168 Japanese patients were assigned to the LEN arm (N = 81) or the SOR arm (N = 87). Median OS was 17.6 months for LEN vs. 17.8 months for SOR (HR 0.90; 95% CI 0.62-1.29). LEN showed statistically significant improvements over SOR in PFS (7.2 months vs. 4.6 months) and ORR (29.6% vs. 6.9%). The relative dose intensity of LEN and SOR in the Japanese population was lower than in the overall population. Frequently observed, related adverse events included palmar-plantar erythrodysaesthesia syndrome (PPES), hypertension, decreased appetite, and proteinuria in the LEN arm, and PPES, hypertension, diarrhea, and alopecia in the SOR arm.
CONCLUSIONS
CONCLUSIONS
The efficacy and safety of LEN in the Japanese population were similar to those in the overall population of REFLECT. With manageable adverse events, LEN is a new treatment option for Japanese patients with uHCC.
TRIAL REGISTRATION ID
BACKGROUND
ClinicalTrials.gov. No. NCT01761266.
Identifiants
pubmed: 31720835
doi: 10.1007/s00535-019-01642-1
pii: 10.1007/s00535-019-01642-1
pmc: PMC6942573
doi:
Substances chimiques
Antineoplastic Agents
0
Phenylurea Compounds
0
Quinolines
0
Sorafenib
9ZOQ3TZI87
lenvatinib
EE083865G2
Banques de données
ClinicalTrials.gov
['NCT01761266']
Types de publication
Clinical Trial, Phase III
Comparative Study
Equivalence Trial
Journal Article
Multicenter Study
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
113-122Subventions
Organisme : Eisai Inc.
ID : N/A
Organisme : Merck Sharp & Dohme Corp.
ID : N/A
Organisme : Eisai
ID : N/A
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