Randomized phase II trial comparing the efficacy and safety of nintedanib versus sorafenib in patients with advanced hepatocellular carcinoma (HCC).

Abstract

238 Background: Nintedanib (N) is an oral, triple angiokinase inhibitor of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF) receptors. This randomized, multicenter, open-label, phase II study (NCT01004003; 1199.37) evaluated the efficacy and safety of N versus sorafenib (S) in patients with advanced HCC. Methods: Enrolled patients had unresectable advanced HCC, ECOG-PS ≤2, Child–Pugh score 5–6, alanine/aspartate aminotransferase (ALT/AST) ≤2× upper limit of normal, and ≥1 untreated measurable lesion or a previously treated lesion with progression (by RECIST 1.0). Patients were randomized 2:1 to N 200 mg bid or S 400 mg bid continuously in 28-day cycles, until intolerable adverse events (AEs) or disease progression (PD); treatment beyond PD was allowed if clinical benefit was perceived. Primary endpoint was time to progression (TTP) by independent central review (ICR; RECIST 1.0), and secondary endpoints were overall survival (OS) and investigator-assessed (IA) TTP. Results: Ninety-three patients were randomized to receive N (n=62) or S (n=31). At the cutoff date (15 July 2014), 77% of patients had a TTP event, and 70% had an OS event; 3 patients remained on treatment with 1 patient beyond PD. IA TTP was comparable between N and S (median 5.5 vs 3.8 months; HR 1.05 [95% CI: 0.63–1.76]), as was OS (median 11.9 vs 11.4 months; HR 0.88 [95% CI: 0.52–1.47]). ICR TTP data are pending. All patients reported an AE (CTCAE 3.0); more patients treated with S had Grade ≥3 AEs (68% vs 90%). AEs leading to dose reduction were higher with S (19% vs 42%), whereas AEs leading to drug discontinuation were higher with N (45% vs 23%). The only tyrosine kinase inhibitor class-specific AE reported in >15% of patients was hand-foot skin reaction in the S arm. AEs previously observed with N and higher in this arm were diarrhea, vomiting, nausea, and AST increase, while blood bilirubin increase was higher with S. Rash was reported in >15% of patients only in the S arm. Conclusions: N shows similar efficacy to S with respect to TTP and OS, with a manageable safety profile. Further studies of N in patients with advanced HCC are warranted. Clinical trial information: NCT01004003.