Apatinib significantly increases overall survival in patients with pretreated advanced hepatocellular carcinoma compared with placebo, with a manageable safety profile, according to a study in the Lancet Gastroenterology & Hepatology.
The randomized, double-blind, placebo-controlled, phase 3 AHELP trial was conducted at 31 hospitals in China (ClinicalTrials.gov identifier: NCT02329860). Eligible patients were aged 18 years or older with histologically or cytologically confirmed or clinically diagnosed advanced hepatocellular carcinoma. Patients had been refractory or intolerant to previous systemic chemotherapy, targeted therapy, or both.
Participants received apatinib 750 mg (three 250-mg tablets) or placebo (3 tablets) orally, once daily in 28-day cycles. Overall survival was the primary endpoint.
A total of 400 patients were randomly assigned to apatinib (n=267) or placebo groups (n=133) from April 1, 2014, to May 3, 2017; 6 patients in the apatinib group and 1 in the placebo group did not receive treatment and were excluded from the full analysis. Participants had a median age of 51 years (range, 25-78 years), and 86% were men. In addition, 340 (87%) patients had hepatitis B virus (HBV) infection and 160 (41%) had received sorafenib.
On the data cutoff date of December 15, 2017, 312 overall survival events occurred, and the median follow-up was 7.6 months (interquartile range, 4.6-13.0 months).
Apatinib significantly improved overall survival compared with placebo (hazard ratio [HR] 0.785; 95% CI, 0.617-0.998]; P =.048). The median overall survival was 8.7 months (95% CI, 7.5-9.8) in the apatinib group compared with 6.8 months (95% CI, 5.7-9.1) in the placebo group.
A total of 387 patients (257 in the apatinib group and 130 in the placebo group) were included in the safety set. The median treatment exposure duration was 3.6 months (range, <0.1-28.7 months) for the apatinib group and 1.8 months (range, 0.2-19.2 months) for the placebo group.
Treatment-related adverse events (TRAEs) occurred in 250 (97%) patients in the apatinib group and in 92 (71%) patients who received placebo. Grade 3 or 4 TRAEs occurred in 199 (77%) patients in the apatinib group and 25 (19%) in the placebo group, and serious adverse events occurred in 95 (37%) patients in the apatinib group and 30 (23%) in the placebo group.
The most frequently occurring TRAEs were hand–foot syndrome (144 [56%] of 257 patients in the apatinib group vs 5 [4%] of 130 patients in the placebo group) and hypertension (123 [48%] vs 17 [13%], respectively).
Apatinib also significantly improved progression-free survival compared with placebo (median, 4.5 months vs 1.9 months; HR 0.471; 95% CI, 0.369-0.601), and the proportion of patients with an objective response was greater in the apatinib group (11%) vs the placebo group (2%).
The investigators noted that future studies are needed to validate the efficacy and safety of apatinib in patients with advanced hepatocellular carcinoma who have previously received tyrosine kinase inhibitor agents. Also, AHELP primarily enrolled patients with HBV infection, limiting the ability for cross-comparison among other etiologies.
Disclosures: The study was funded by Jiangsu Hengrui Medicine. Some of the study authors are employees of Jiangsu Hengrui Medicine. Please see the original reference for a full list of disclosures.
Qin S, Li Q, Gu S, et al. Apatinib as second-line or later therapy in patients with advanced hepatocellular carcinoma (AHELP): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Gastroenterol Hepatol. Published online May 7, 2021. doi: 10.1016/S2468-1253(21)00109-6