Based on the phase III REFLECT study, lenvatinib (LEN) has been recommended as a first-line (1L) therapy for uHCC since 2018. Recent years have seen a further expansion of 1L treatment recommendations for uHCC, to include atezolizumab+bevacizumab, nivolumab, FOLFOX4 and donafenib. We conducted a network meta-analysis (NMA) to compare the efficacy and safety of lenvatinib with other systemic therapies in first-line uHCC.
A systematic literature review identified randomized, controlled, multicenter trials in adults with advanced HCC who had received no prior systemic therapy. Literature retrieval was conducted using PubMed, ScienceDirect, the Cochrane Database, EMBASE and other sources. Objective response rate (ORR), disease progression-free survival (PFS), time-to-progression (TTP) and treatment discontinuations due to adverse events (AEs) were extracted from published studies and quantitatively pooled using frequentist NMA. Pairwise risk ratio(RR), hazard ratio(HR) with confidence interval was calculated. The P-scores were used to rank each treatment.
In total, 1398 records were screened and 27 were eligible for analysis, and the treatments included were atezolizumab+bevacizumab, brivanib, FOLFOX4, donafenib, dovitinib, lenvatinib, linifanib, nintedanib, nivolumab, sorafenib, sunitinib, vandetanib, 11 sorafenib combination therapies and three other combination therapies. For ORR and TTP, lenvatinib was ranked first (P-scores: 0.88 and 0.99), for PFS, atezolizumab+bevacizumab was ranked first followed by lenvatinib (HR: 0.89; 95% CI, 0.64-1.25; P-scores: 0.95 and 0.90) and donafinib and nivolumab ranked 5th and 6th (HR: 1.38; 95% CI, 1.09-1.73, HR: 1.41; 95% CI, 1.13-1.76; P scores: 0.90 vs 0.59 vs 0.56 respectively). Atezolizumab+bevacizumab was associated with the highest probability of discontinuation due to AEs (RR: 1.27 [0.35-4.60]), lenvatinib ranked 4th (P scores: 0.25 and 0.39, respectively).
This NMA suggested that greater ORR and TTP benefits with first-line use of Lenvatinib than others. Although Atezolizumab+Bevacizumab showed more benefit in PFS, more discontinuation because of AE should also take into consideration.
The authors.
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All authors have declared no conflicts of interest.