The addition of sorafenib to transarterial chemoembolization improved PFS among patients with unresectable hepatocellular carcinoma, according to results of a randomized phase 2 trial presented at the Gastrointestinal Cancers Symposium.
Studies have shown sorafenib (Nexavar, Bayer), a synthetic compound targeting growth signaling and angiogenesis, did not significantly extend time to progression for patients with advanced HCC after transarterial chemoembolization.
Whether a combination of sorafenib with transarterial chemoembolization — an image-guided, nonsurgical procedure that is uses an X-ray-guided catheter to deliver chemotherapy and embolization materials into liver blood vessels — prolonged PFS or OS compared with transarterial chemoembolization alone remained unclear.
Masatoshi Kudo, MD, PhD, from the department of gastroenterology and hepatology at Kindai University in Osaka-Sayama, Japan, and colleagues conducted an open-label trial at 33 institutions. Researchers randomly assigned 156 patients to transarterial chemoembolization (n = 76) or sorafenib plus transarterial chemoembolization (n = 80).
At baseline, all patients had unresectable HCC, Child-Pugh scores of 7 or less, ECOG performance status of 0 to 1, no vascular invasion or extrahepatic spread, and proper organ function.
Researchers pretreated patients in the combination group with 400 mg sorafenib once daily for 2 to 3 weeks prior to transarterial chemoembolization. Patients then received 800 mg once daily during conventional transarterial chemoembolization sessions until untreatable progression, defined as the length of time to when transarterial chemoembolization sessions were no longer possible due to untreatable tumor progression, deterioration of Child-Pugh C, or vascular invasion and extrahepatic spread.
PFS and OS served as the primary endpoints. Secondary endpoints included time to progression and safety.
Researchers anticipated a target HR of 0.71 and power of 0.8, with a 40% extension in PFS from 18 months in the control group to 25 months in the combination arm.
Patients treated with transarterial chemoembolization alone demonstrated shorter PFS than those in the combination group (13.5 months vs. 25.2 months; HR = 0.59; 95% CI, 0.41-0.87).
The monotherapy group also demonstrated shorter median time to progression (13.5 months vs. 24.1 months; HR = 0.56; 95% CI, 0.38-0.83). The median time to untreatable progression was 20.6 months in the monotherapy group compared with 26.7 months in the combination group (HR = 0.57; 95% CI, 0.35-0.92).
The number of OS events was not reached at the time of analysis.
Researchers observed no unexpected toxicities.
“Adverse events were consistent with the known safety profile with previous [transarterial chemoembolization] combination trials,” the researchers wrote. – by Melinda Stevens
Kudo M, et al. Abstract 206. Presented at: Gastrointestinal Cancers Symposium; Jan. 18-20, 2018; San Francisco.
Disclosures: Kudo reports consultant roles with Bayer, Bristol-Myers Squibb, Chugai Pharma, Kowa and Taiho Pharmaceutical; honoraria from Ajnomoto, Bayer and Eisai; and research funding from AbbVie, Bayer, Chugai Pharma, Daiichi Sanyko, Eisai, Merck, Otsuka, Sumitomo Dainippon, Taiho Pharmaceutical and Takeda. Please see the abstract for all other authors’ relevant financial disclosures.