Abstract
BackgroundA 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.MethodsThe intent-to-treat population enrolled in Japan was analyzed.ResultsOf 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.ConclusionsThe 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 IDClinicalTrials.gov. No. NCT01761266.
Highlights
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and one of the major causes of cancer-related deaths worldwide [1,2,3,4]
In the analysis of the secondary efficacy endpoints that were determined by the investigator assessment based on mRECIST, lenvatinib was superior to sorafenib for progression-free survival (PFS), with a median of 7.2 vs. 4.6 months and an hazard ratio (HR) of 0.63 (0.44–0.90; P = 0.0104; Fig. 1b and Table 2), and time to progression (TTP), with a median of 7.2 vs. 4.6 months and an HR of 0.62 (0.43–0.89; P = 0.0087)
Significant improvement with lenvatinib vs. sorafenib was shown in the objective response rate (ORR) (CR ? partial response (PR)), 29.6% vs. 6.9%, with an odds ratio [OR] of 7.03 (2.46–20.09; P = 0.0001)
Summary
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and one of the major causes of cancer-related deaths worldwide [1,2,3,4]. Despite the overall survival rate of HCC patients being considerably improved with advances of diagnostic measures and treatment modalities [3, 6], patients often experience recurrence of the disease and face limited treatment options with advanced disease. This is because HCC frequently develops in patients with chronic liver disease, cirrhosis in particular, which may lead to a limited prognosis after surgical resection [1, 3].
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