Independent imaging review (IIR) results in a phase 3 trial of lenvatinib (LEN) versus sorafenib (SOR) in first-line treatment of patients (pts) with unresectable hepatocellular carcinoma (uHCC).

345 Background: LEN showed treatment effect on OS by statistical demonstration of noninferiority to SOR in a phase 3 study in pts with uHCC, with significant improvement ( P < 0.00001) in median PFS (7.4 vs 3.7 mos; HR: 0.66; 95% CI, 0.57−0.77), median TTP (8.9 vs 3.7 mos; HR: 0.63. 95% CI, 0.53−0.73), and ORR (24% vs 9%). Tumor assessments were by investigator review (IR) per modified RECIST (mRECIST). We present IIR results to assess concordance for IR vs IIR and mRECIST vs RECIST 1.1 by IIR. Methods: In this open-label study, pts with uHCC, ≥ 1 measurable target lesion, BCLC stage B or C, Child-Pugh class A, ECOG PS ≤ 1, and no prior systemic therapy were randomized 1:1 to LEN (body weight ≥60 kg: 12 mg/d; <60 kg: 8 mg/d) or SOR 400 mg twice daily. Primary endpoint was OS. Secondary efficacy endpoints were PFS, TTP, and ORR by mRECIST. IR tumor assessments were done every 8 wks. Post hoc exploratory blinded IIR studies were done using mRECIST and RECIST 1.1 (first timepoint at wk 8). Results: A total of 954 pts enrolled (LEN: 478; SOR: 476), of which 952 (99.8%) pts were IIR assessable (table). Adjudication rate (AR; percentage of cases adjudicated due to disagreement) for timepoint of PD was similar for mRECIST (47%) and RECIST 1.1 (45%); for responder (CR or PR)/nonresponder (SD, PD, or not evaluable [NE]), it was 32% for mRECIST and 17% for RECIST 1.1. PFS and TTP results were nearly the same per mRECIST by IIR as by IR and the same by IIR per mRECIST and RECIST 1.1. Very good concordance was seen between IIR and IR in best overall response (BOR) per mRECIST with the greatest discordance due to more pts being assessed as PR than SD for LEN. Conclusions: IIR supports IR results. ORR was higher in both arms by IIR vs IR but relative ORR was preserved in LEN vs SOR. Higher AR for IIR per mRECIST on response may be due to the greater number of responders or disease complexity. Median PFS and TTP were the same by IIR per mRECIST and RECIST 1.1, showing these data can be compared between methods. Clinical trial information: NCT01761266. [Table: see text]