In a phase 3 randomized controlled study (RCT) lenvatinib (LEN) demonstrated significantly better progression-free survival (PFS) vs sorafenib (SOR) in treatment-naive (1L) uHCC patients. Prior SOR RCTs had been conducted vs placebo (PBO). Our aim was to synthesize all efficacy evidence enabling a comparison of both LEN and SOR to PBO.
EMBASE®, MEDLINE®, MEDLINE® in-process, and Cochrane databases were systematically searched through February 2017 for relevant RCTs in 1L uHCC. Data from the recently completed LEN RCT were added to the review. A conventional NMA based on PFS and overall survival (OS) was performed using a frequentist random effect NMA programmed in R-3.3.1. PBO was used as the reference treatment.
3 Studies met inclusion criteria: 1 recently completed LEN vs SOR study (N = 954) and 2 RCTs comparing SOR to PBO: (1) Llovet 2008 (N = 602) and (2) Cheng 2009 (N = 226). The 3 RCTs were generally comparable with some variability in patient baseline characteristics: mean age, years (63, 66, 61), % male (84, 87, 85), % ECOG score 0-1 (100, 93, 95), % Child–Pugh class A (99, 97, 97), and % prior hepatitis B/C (50/23, 19/28, 73/8) in LEN vs SOR, SOR vs PBO (1), and SOR vs PBO (2), respectively. In the NMA vs PBO, LEN and SOR yielded indirect hazard ratios (HRs) of 0.38 and 0.58 for PFS and 0.63 and 0.69 for OS, respectively. Using LEN as a common comparator, SOR and PBO yielded indirect HRs of 1.52 and 2.63 for PFS and 1.09 and 1.58 for OS, respectively (Table).
This NMA demonstrated that for 1L uHCC patients, both LEN and SOR demonstrated significantly better PFS vs PBO: 62% progression risk reduction for LEN vs 42% for SOR.Table:
|Intervention||PFS HR (95% CI)||OS HR (95% CI)|
|PBO – Comparator|
|LEN||0.38 (0.30; 0.49)||0.63 (0.50; 0.80)|
|SOR||0.58 (0.47; 0.70)||0.69 (0.57; 0.83)|
|LEN – Comparator|
|SOR||1.52 (1.30; 1.76)||1.09 (0.94; 1.26)|
|PBO||2.63 (2.06; 3.36)||1.58 (1.25; 2.00)|
Clinical trial identification
Legal entity responsible for the study
G. Meier, D. Misurski, M. Baig, T. Tamai: Employee of Eisai Inc. S. Kraljevic: Employee of Eisai Co Ltd. All other authors have declared no conflicts of interest.