Hand-foot syndrome may predict better outcomes after sorafenib for HCC

Among patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib, those with hand-foot syndrome (HFS) who were able to receive post-progression treatment had good overall survival (OS). The data suggest that this side effect is important for preserving the remaining hepatic reserve, according to a study published in Oncology.

The multi-center study was led by Chikara Ogawa, MD, at the Kindai University Faculty of Medicine in Osaka-Sayama, Japan. The team examined the relationship between treatment outcomes and HFS, as well as the relationship between survival rate and post-progression treatment after sorafenib therapy.

Sorafenib is a multi-targeted tyrosine kinase inhibitor that suppresses tumor proliferation and angiogenesis. It has been shown to improve the time to progression and OS in advanced HCC with vascular invasion and/or extrahepatic spread. In Japan, it is the standard of care for systemically treated patients.

Prior studies have reported improved therapeutic results in patients who exhibited HFS compared to those who did not report HFS. For this study, 314 patients with advanced HCC based on histological or radiological findings were treated with sorafenib in five general hospitals in Japan from June 2009 to January 2016.

The study included 254 men and 60 women—mean age was 72.5 ± 9.46 years. Patients presented with hepatitis B virus infection (n=43), hepatitis C virus infection (n=175), and other forms of liver disease (n=96). HCC was newly diagnosed in 57 patients, and it had recurred in 257 patients. There were 295 patients with a history of treatment for HCC; 19 had no prior treatment.

The initial recommended dose of sorafenib was 800 mg/day. However, a large study in Japan found little difference between a starting dose of 400 mg/day or 800 mg/day, due to the smaller body surface area in most Japanese patients when compared with those in Europe and the Americas. The mean initial sorafenib dose in this study was 391.7 ± 159 mg/day (range: 200 mg to 800 mg).

The Child-Pugh class and score at the initiation of sorafenib therapy was A-5 points (n=129), A-6 points (n=111 patients), B-7 points (n=48 patients), and B-8 points or higher (n=26 patients).

Sorafenib therapy was initiated in stage I (n=6), stage II (n=51), stage III (n=85), stage IVa (n=58), and stage IVb (n=114) patients.

The mean observation period in the present study was 223 ± 277 days (range: 2 to 1,665 days).

The indications for sorafenib treatment included distal metastasis, unresponsiveness to hepatic trans-arterial chemoembolization (TACE), inability to perform TACE, severe vascular invasion (10.8%), and other reasons (1.0%).

Distant metastasis was noted in the lung (n=54), bone (n=39), lymph nodes (n=36), adrenal glands (n=14), and peritoneal cavity (n=13); some patients had metastases to multiple sites.

In this study, time to progression after sorafenib therapy was 129 ± 21.3 days, and median survival time (MST) was 392 ± 38.8 days. A complete response, partial response, stable disease, progressive disease, and incomplete evaluation were observed in 10, 25, 113, 147, and 19 patients, respectively. The overall response rate was 11.1%, and the tumor control rate was 47.4%.

An initial sorafenib dose of 200 mg was administered to 77 patients; 400 mg was given to 202 patients; 600 mg was given to 6 patients; and 800 mg was given to 29 patients. The mean duration of sorafenib therapy was 223.6 days.

Regarding survival rate, Child-Pugh class A was significantly better when compared with class B. Furthermore, OS in those with class A-5 points was significantly better than class A-6 points; however, OS was not significantly different between Child-Pugh class A-6 points and class B. The best OS was observed when treatment was initiated at Child-Pugh class A-5 points.

During the observation period, HFS was observed in 118 patients (37.6%), with a mean number of days until onset of 29.6 ± 33.8 (range: 1 to 227 days). Adverse effects were observed in 43 patients with grade I HCC (14.0%), 42 with grade II HCC (13.8%), and 24 with grade III HCC (7.9%).

Of the patients who exhibited HFS, days to onset was less than one month after initiation of sorafenib therapy in 65.3%. Mean survival of patients with HFS was 487 days, compared to 292 days in those without HFS.

The MST of patients who underwent post-progression treatment after sorafenib therapy was 456 days, and 233 days for those who were not treated; OS was better for those who underwent post-progression treatment.

The benefit of post progression treatment after sorafenib has previously been reported. The investigators suggested that the good OS results achieved even against a background of poor liver function in this study are largely due to starting at an optimal stage when liver function is still preserved.

The investigators also point out that methods of preventing and treating HFS have been established since sorafenib was introduced, so the results were likely less affected by dropouts due to HFS compared to when the drug was first approved. Previously, patients who exhibited HFS had better results than those who did not; a similar trend was also observed in this study.

“The best results were observed when therapy was initiated at Child-Pugh class A-5 points, which indicates that it is preferable to start sorafenib at the time when liver function is still well preserved,” concluded the authors.

In addition, patients who exhibited HFS who received post-progression treatment after sorafenib therapy had good OS, which suggests that addressing and managing this side effect is important for preserving the remaining hepatic reserve.

To read more about this study, click here.