Tigatuzumab/Nexavar combination fails to improve advanced HCC

Researchers found that tigatuzumab in combination with Nexavar was not effective in treating patients with advanced hepatocellular carcinoma, according to phase 2 clinical trial data published in the Journal of Hepatology.

Researchers began the clinical study with safety cohorts receiving escalating maintenance doses of tigatuzumab (Daiichi Sankyo) with regular doses of Nexavar (sorafenib, Bayer), who then reached “steady-state levels” of repeated dosing, according to the research. Overall, 163 adults with advanced HCC from 28 clinical sites in Japan, South Korea, Taiwan and the U.S., were randomly assigned to a combination regimen of either tigatuzumab (6 mg/kg loading, 2 mg/kg/week maintenance) plus 400 mg of sorafenib twice daily; tigatuzumab (6 mg/kg loading, 6 mg/kg/week maintenance) plus 400 mg of sorafenib twice daily; or 400 mg of sorafenib alone twice daily.

“The primary endpoint was time to progression, [with] secondary endpoints including overall survival and safety,” the researchers wrote.

Overall, none of the patients showed a complete response to therapy. The median time to progression was 3 months among patients who received 6 mg/2 kg of tigatuzumab (P = .988 vs. sorafenib); 3.9 months among patients who received 6 mg/6 kg of tigatuzumab (P = .586 vs. sorafenib); and 2.8 months among patients treated with sorafenib alone. Only 11 patients remained in the study at the primary analysis cutoff date due to the fact that 152 discontinued treatment because of disease progression, according to the research.

“The [time to progression] as assessed by independent radiological review showed similar results, especially in the higher dose [tigatuzumab] and [sorafenib] alone groups,” the researchers wrote.

The median overall survival was highest among patients who received 6 mg/2 kg of tigatuzumab (12.2 months; P = .659 vs. sorafenib) compared with 8.2 months for both of the other treatment groups (P = .303 vs. sorafenib).

A total of 75.9% of patients treated with tigatuzumab (88/116) experienced treatment-emergent adverse events, with palmar-plantar erythrodysesthesia syndrome, diarrhea and decreased appetite being the most common. A total of 98.3% of patients treated with sorafenib (114/116) experienced treatment-emergent adverse events due to sorafenib.

The most common serious adverse event related to tigatuzumab treatment were ascites (n = 5) and hepatic encephalopathy related to sorafenib (n = 4).

The researchers concluded: “Tigatuzumab in combination with sorafenib vs. sorafenib alone in adults with advanced HCC did not meet its primary efficacy endpoint, although the combination is well-tolerated. “ – by Melinda Stevens

Disclosures: Cheng reports being a consultant for Daiichi Sankyo Inc., Merck Serono, Eisai, Jennerex and Exelixis; and has received research funding from Aanofi-Chugai and MSD. Please see the study for a full list of all other authors’ relevant financial disclosures.