<p>Safety and Efficacy of Lenvatinib Treatment in Child–Pugh A and B Patients with Unresectable Hepatocellular Carcinoma in Clinical Practice: A Multicenter Analysis</p>

Abstract

Purpose To assess the safety, efficacy and prognostic impact of clinical factors related to lenvatinib treatment in Child-Pugh class A (CP-A) and class B (CP-B) patients with unresectable hepatocellular carcinoma (u-HCC). Methods Patients with u-HCC who were treated with lenvatinib at multiple centers in Japan were retrospectively analyzed for treatment outcomes according to their respective CP status. Radiological objective response (OR) was assessed using modified response evaluation criteria in solid tumors (mRECIST) guidelines. Results Baseline demographic parameters were comparable between 126 (69.6%) patients with CP-A disease and 55 patients (30.4%) with CP-B disease. Frequency of lenvatinib-related adverse events, including decreased appetite (P=0.034), diarrhea (P=0.040), elevated serum bilirubin (P=0.016) and vomiting (P=0.009), were higher in CP-B than in CP-A patients. Relative dose intensity (RDI) was significantly higher in CP-A (0.69) than CP-B patients (0.50, P <0.001). Furthermore, OR rate (44.0%) was markedly higher in CP-A5 patients as compared to CP-A6 (25.5%), CP-B7 (22.2%), and CP-B8 patients (5.3%), respectively (P=0.002). In multivariable analysis, performance status (0 vs 1, 2, P=0.026), CP class (A vs B, P=0.045) and RDI (≥0.7 vs <0.7, P=0.034) were identified as factors associated with response to lenvatinib treatment. Overall survival (OS) at 12 months was significantly different between CP-A (66.3%) and CP-B patients (30.0%, P=0.002), and between CP 5–7 (59.2%) and CP 8 patients (34.8%, P=0.003). In multivariable analysis, CP class (A vs B, P=0.007) and Barcelona clinic liver cancer (BCLC) stage (B vs C, P=0.002) were associated with OS following lenvatinib treatment. Conclusion Lenvatinib treatment offers significant benefits in patients with good liver function in real-world practice. The various characteristics identified in this study might be helpful as clinical predictors of response to lenvatinib and survival in clinical practice. Further studies are required to address eligibility for lenvatinib treatment in CP 7 patients.

Lenvatinib for Hepatocellular Carcinoma: A Literature Review

“…Many real-world studies have reported the short-term therapeutic response of lenvatinib, resulting in an ORR of 29.9-53.5%, as assessed by mRECIST [17][18][19][20][21][22][23][24], and 14-25%, as assessed by RECIST ver.1.1 [19,22,25,26]. These findings seemed to be in agreement with the results of phase 2 and 3 studies (Table 1).…”

“…We reported that BCLC intermediate stage was a significant predictive factor that was associated with the ORR in a multivariate analysis [18], which agreed with the results regarding the ORRs in the analysis of a Japanese subpopulation in the REFLECT trial [27]. A high ORR was found in patients with a good PS [21], Child-Pugh class A [21], and Child-Pugh score 5 (CP-5A) [23]. Some of the researchers also reported that the high relative dose intensity (RDI) at four weeks (30 days) [23,28,29] or eight weeks (60 days) [19,21,30,31] was relevant to therapeutic response of lenvatinib, including the PFS and OS ( Table 2).…”

“…The median OS was 13.6 months (95% CI 12.1-14.9) in a phase 3 study [12]. The median OS was shown to be 7.1-13.3 months, according to some retrospective studies [19,21,22,26], and modified ALBI (mALBI) grade 2b or 3 [24], Child-Pugh class B [21], BCLC advanced stage [21,35], and elevated C-reactive protein [36] were found to be significant unfavorable factors. While the starting dose of sorafenib did not influence OS according to one retrospective study [37], the patients with the higher RDI of lenvatinib (>67%) at eight weeks had significantly better OS in comparison to those with lower RDI (≤67%) [19].…”

“…A high ORR was found in patients with a good PS [21], Child-Pugh class A [21], and Child-Pugh score 5 (CP-5A) [23]. Some of the researchers also reported that the high relative dose intensity (RDI) at four weeks (30 days) [23,28,29] or eight weeks (60 days) [19,21,30,31] was relevant to therapeutic response of lenvatinib, including the PFS and OS ( Table 2). The cut-off values of the RDI were similar, ranging from 66% to 75%.…”

“…Adverse events that were frequently reported in many previous studies included fatigue, appetite loss, hand-foot skin reaction (HFSR), diarrhea, hypertension, hypothyroidism, and proteinuria [12,18,[21][22][23][24]40]. The rate of discontinuation due to AEs was 8.6-43.5% [18,22,40].…”