Combining Sorafenib and Transarterial Chemoembolization Extends Progression-Free Survival in Patients with Hepatocellular Carcinoma
Sorafenib (Nexavar) in combination with transcatheter arterial chemoembolization (TACE) significantly improves progression-free survival (PFS), with no unexpected adverse results, compared with TACE alone in patients with unresectable hepatocellular carcinoma (HCC), according to results from the phase 2 TACTICS clinical trial.
The median PFS was nearly twice as long in the sorafenib plus TACE group than with TACE alone, said Masatoshi Kudo, MD, PhD, Department of Gastroenterology and Hepatology, Kindai University, Osaka, Japan, at the 2018 Gastrointestinal Cancers Symposium.
The long duration of sorafenib treatment in the TACTICS study, at 38.7 weeks, may have been the key to the treatment success, he added. In previous trials in which patients with unresectable HCC did not respond to the combination therapy, sorafenib was administered for only 17 to 21 weeks.
“The TACTICS trial clearly showed TACE in combination with sorafenib is a treatment option to improve clinical outcomes, and may be a standard of care in patients with intermediate-stage HCC,” Dr Kudo said.
TACTICS was a randomized, open-label study conducted at 33 centers in Japan. Patients with unresectable HCC, a Child-Pugh score ≤7, no vascular invasion or extrahepatic spread, and adequate organ function were randomized in a 1:1 ratio to receive TACE alone or to TACE plus sorafenib.
In the TACE plus sorafenib group, sorafenib 400 mg once daily was administered for 2 to 3 weeks before the first TACE, followed by sorafenib 800 mg once daily. Sorafenib was interrupted 2 days before and 3 days after each TACE session as long as organ function was maintained. TACE was repeated on demand when the tumor volume increased by 50% from baseline. New intrahepatic lesions were not regarded as progressive disease because it is the natural tumor biology of HCC and does not imply a lack of treatment response, Dr Kudo explained.
The regimen was continued until the time to untreatable progression (TTUP) was achieved, defined as the inability to further receive or derive benefit from TACE, deterioration of liver function to Child-Pugh C, or appearance of vascular invasion or extrahepatic spread, which served as a secondary end point of the study.
Enrollment was halted after the first 156 patients were randomized to their treatment groups. The median PFS was 25.2 months in the TACE plus sorafenib arm compared with 13.5 months for TACE alone, resulting in a hazard ratio (HR) of 0.59 (P = .006). Overall survival data were not yet mature.
The median TTUP was 26.7 months in the TACE plus sorafenib arm versus 20.6 months for TACE alone (HR, 0.57; P = .02). Median time to progression was 26.7 months in the TACE plus sorafenib arm versus 16.4 months for TACE alone, resulting in an HR of 0.54 (P = .005) favoring sorafenib.
Adverse events were consistent with the known safety profile of previous TACE combination therapy trials.
Chronic Liver Problems After Chemoembolization
A real-world study conducted by investigators at Beth Israel Deaconess Medical Center in Boston and presented at the meeting showed “chronic deterioration of liver function after a single TACE in a cohort of patients with HCC.” The data from nearly 600 patients who received TACE suggest that some patients do not fully recover from acute liver damage after TACE.
Led by Rebecca A. Miksad, MD, MPH, Director, Gastrointestinal Medical Oncology, Beth Israel Deaconess Medical Center, the investigators examined US electronic health records to assess liver function in 572 patients with HCC who had undergone TACE. The researchers looked at baseline function and again during the acute period (0-29 days after TACE) and during the chronic period (30-90 days after TACE). Patients’ median age was 62 years.
Dr Miksad and colleagues found deterioration in at least 1 liver function parameter, most often a decrease in albumin levels (31%), in many patients during the chronic period. The investigators also saw a chronic deterioration in total bilirubin (23%), aspartate aminotransferase (30%), alanine aminotransferase (25%), and international normalized ratio (INR; 15%). The deterioration of INR was possibly a result of anticoagulation use after TACE, the investigators cautioned.
“Further characterization of post-TACE chronic deterioration of liver function in HCC, especially in the context of additional treatment, is important, because such deterioration may limit subsequent HCC treatments that are frequently needed for the patient population,” they concluded.