Nintedanib, a triple angiokinase inhibitor, was found to be safe for treating patients with hepatocellular carcinoma and mild or moderate liver impairment, according to data from a phase 1 trial presented at the European Society for Medical Oncology’s European Cancer Congress.
“Nintedanib monotherapy [has already] demonstrated efficacy and a manageable safety profile in phase 1/2 studies of Asian and Caucasian patients with HCC,” the researchers wrote.
Masafumi Ikeda, MD, chief of the department of hepatobiliary and pancreatic oncology, National Cancer Center Hospital East, Kashiwa, Japan, enrolled 30 patients with advanced HCC unamenable to curative surgery or loco-regional therapy and were divided into two groups based on liver function: group 1 consisted of patients with aspartate aminotransferase and alanine aminotransferase levels less than two times the upper limit of normal (ULN) and Child-Pugh score between 5 and 6 (n = 16), group 2 were patients with AST or ALT greater than two times and less than five times the ULN or Child-Pugh score of 7 (n = 14). Group 1 patients were dosed with either 150 or 200 mg twice a day of nintedanib and group 2 patients with either 100, 150 or 200 mg twice a day. The maximum tolerated dose of nintedanib was 200 mg for both groups. Of the patients, 22 had received prior therapy with Nexavar (sorafenib, Bayer Healthcare).
“The primary objective was [maximum tolerated dose] after the first treatment cycle [of 28 days],” the researchers wrote in the abstract.
According to the abstract, dose-limiting toxicities in group 1 included grade 3 diarrhea (n = 1) or grade 3 drug-induced liver injury (n = 1). In group 2, the only dose-limiting toxicity was grade 3 drug-induced liver injury (n = 1). The most frequent adverse events experienced during treatment were: diarrhea (50%), nausea (44%), decreased appetite (38%) and vomiting (38%) in group 1, and decreased appetite (50%), ascites (50%), diarrhea (43%), hypoalbuminemia (43%), nausea (36%), fatigue (36%) and increased AST (36%) in group 2.
“The [adverse events] profile of nintedanib was similar in patients previously treated with sorafenib,” the researchers wrote.
In group 1, 31% of patients underwent dose reduction of nintedanib due to adverse events, as well as 21% in group 2. However, no patients discontinued treatment due to adverse events.
At the end of 28 days of treatment, 15 of 16 patients in group 1 and all 14 patients in group 2 had a time to progression event. The median investigator-assessed time to progression was 2.8 months (95% CI, 1.1-5.5) in group 1 and 3.2 months (95% CI, 1-6.7) in group 2.
The researchers concluded: “In Japanese patients with HCC and mild or moderate liver impairment, the maximum tolerated dose for Nintedanib of 200 mg [twice a day] is the same as previously observed for other Asian and Caucasian patients with HCC. Nintedanib has a manageable safety profile with no unexpected adverse events, and promising efficacy signals in prior [sorafenib]-treated patients that warrants further study.”
Ikeda M, et al. Abstract 2356. Presented at: European Cancer Congress; Sept. 25-29, 2015; Vienna.
Disclosures: Ikeda reports serving on the advisory board for Bayer Yakuhin; and receiving grants and/or research support from the National Cancer Center Research and Development Fund, Ministry of Health, Labour, and Welfare of Japan, Bayer Yakuhin, Novartis Pharma, Merck Serono, Kyowa Hakko Kirin, Yakult, Dainippon Sumitomo, Taiho Pharmaceutical, Eli Lilly Japan, Otsuka Pharmaceutical, Chugai Pharmaceutical, OncoTherapy Science, Boehringer Ingelheim, Kowa, Ono Pharmaceutical, Eisai, AstraZeneca, Pfizer Japan, GlaxoSmithKline and Zeria Pharmaceutical. Please see the abstract for a full list of all other authors’ relevant financial disclosures.