Orantinib plus conventional transcatheter arterial chemoembolization (cTACE) does not improve overall survival (OS) over cTACE alone among patients with unresectable hepatocellular carcinoma, according to a study published in The Lancet Gastroenterology & Hepatology.1
TACE is associated with significant risks such as metastasis, liver dysfunction, and incomplete tumor necrosis. A previous study demonstrated that TACE plus orantinib insignificantly prolonged progression-free survival (PFS), though it did not improve OS.
For the double-blind, phase 3 ORIENTAL study (ClinicalTrials.gov Identifier: NCT01465464) researchers randomly assigned 889 patients with hepatocellular carcinoma to receive oral orantinib 200 mg twice daily or placebo within 28 days of cTACE. The median follow-up was 17.3 months.
Patients in the orantinib arm had a median OS of 31.1 months (95% CI, 26.5-34.5) vs 31.1 months (95% CI, 28.4-not reached) in the placebo arm (hazard ratio [HR], 1.090; 95% CI, 0.878-1.352; P = .435).
The study also failed to demonstrate an improvement of median time to TACE failure and time to treatment failure for patients receiving orantinib, but the orantinib arm did achieve a median time to progression of 2.9 months (95% CI, 2.8-3.0) vs 2.5 months (95% CI, 1.4-2.9) in the placebo arm (HR, 0.858; 95% CI, 0.744-0.990; P = .0356).
The trial was terminated early citing futility.
The main adverse events (AE) experienced by patients in the orantinib arm included an elevation of liver function enzymes, edema, and ascites. The most frequently reported grade 3 or greater AEs in the orantinib arm and placebo arm were elevated aspartate aminotransferase (43% vs 36%, respectively), elevated alanine aminotransferase (34% vs 30%), and hypertension (11% vs 9%).
Serious adverse were reported by 45% and 30% of patients in the orantinib and placebo arms, respectively.
The authors concluded that “more refined trial designs, more applicable endpoints, and concomitant use of more potent and less toxic targeted agents should be explored in future TACE combination trials.”
- Kudo M, Cheng AL, Park JW, et al. Orantinib versus placebo combined with transcatheter arterial chemoembolisation in patients with unresectable hepatocellular carcinoma (ORIENTAL): a randomised, double-blind, placebo-controlled, multicentre, phase 3 study. Lancet Gastroent Hepato. 2017 Oct 4. doi: 10.1016/S2468-1253(17)30290-X [Epub online ahead of print]