Clinical outcomes of patients with advanced hepatocellular carcinoma treated with sorafenib: a retrospective study of routine clinical practice in multi-institutions

Abstract

BackgroundSorafenib is an orally administered multikinase inhibitor with antiangiogenic and antiproliferative properties. The results of large clinical trials demonstrate that sorafenib prolongs survival and the time to progression of patients with advanced hepatocellular carcinoma (HCC). The aim of the present study was to determine the outcomes of such patients who were routinely treated with sorafenib at multi-institutions in Korea, in contrast to formal clinical trials.MethodsBetween August 2007 and March 2012, patients with advanced HCC in seven referral medical centers in Daejeon-Chungcheong Province of Korea were retrospectively enrolled to evaluate treatment response, survival, and tolerability following administration of sorafenib. The treatment response was assessed in accordance with the Response Evaluation Criteria in Solid Tumor 1.1 guidelines.ResultsAmong 116 patients, 66 (57%) had undergone treatment for HCC, and 77 (66%) were accompanied with Child-Pugh A cirrhosis. The median duration of sorafenib treatment was 67 days (range 14–452 days). Median overall survival and median time to progression were 141 days and 90 days, respectively. Complete response, partial response, and stable disease were achieved for 0%, 2%, and 29% of patients, respectively. Overall median survival, but not the median time to progression, was significantly shorter for patients with Child-Pugh B cirrhosis compared with those with Child-Pugh A cirrhosis (64 days vs 168 days, P = 0.004). Child-Pugh B cirrhosis (P = 0.024) and a high level of serum alpha-fetoprotein (P = 0.039) were independent risk factors for poor overall survival. Thirty-nine (34%) patients experienced grade 3/4 adverse events such as hand-foot skin reactions and diarrhea that required dose adjustment.ConclusionsThe clinical outcomes of sorafenib-treated patients with advanced HCC were comparable to those reported by formal clinical trial conducted in the Asia-Pacific region. Underlying hepatic dysfunction was the most important risk factor for shorter survival.

Nivolumab in patients with advanced hepatocellular carcinoma and Child‐Pugh class B cirrhosis: Safety and clinical outcomes in a retrospective case series

“…[27][28][29] Although >80% of subjects experienced SAEs, the majority of these were associated with complications of comorbid liver dysfunction and advanced tumor burden, as has been observed in other studies of patients with CPB HCC, 7,9,11 and treatment-related grade ≥3 events were reported to have occur red in only 28% of patients. [27][28][29] Although >80% of subjects experienced SAEs, the majority of these were associated with complications of comorbid liver dysfunction and advanced tumor burden, as has been observed in other studies of patients with CPB HCC, 7,9,11 and treatment-related grade ≥3 events were reported to have occur red in only 28% of patients.…”

“…To the best of our knowledge, the current retrospective case series is the first analysis of the safety and efficacy of nivolumab in patients with HCC and CPB cirrhosis, which is a growing population with a poor prognosis and limited treatment options. [27][28][29] Although >80% of subjects experienced SAEs, the majority of these were associated with complications of comorbid liver dysfunction and advanced tumor burden, as has been observed in other studies of patients with CPB HCC, 7,9,11 and treatment-related grade ≥3 events were reported to have occur red in only 28% of patients. The overall rates of AEs attributed to nivolumab were similar to the rates reported in CPA HCC cohorts in the CheckMate 040 trial, 23 studies of nivolumab in other solid tumors, 30 and rates reported in the CheckMate 040 trial CPB HCC cohort.…”

Targeting the Ras/Raf/MEK/ERK pathway in hepatocellular carcinoma

“…For example, sorafenib is a Raf-1 kinase inhibitor and is the only approved drug therapy for HCC. In patients with advanced or metastatic HCC and compensated cirrhosis, sorafenib offers disease control in ~40% of treated patients, with a time to progression of 5.5 months and a median survival time of 10.7 months, ~3 months longer than that of placebo-treated patients (8). Hence, there is an eagerness to dissect the molecular mechanisms of invasion and metastasis for novel insights and interventions against the recurrence of HCC.…”

Skeletal muscle mass is associated with toxicity, treatment tolerability, and additional or subsequent therapies in patients with hepatocellular carcinoma receiving sorafenib treatment

“…Regarding the association between treatment duration and survival, two previous studies have demonstrated that the duration of sorafenib treatment is an independent risk factor for survival. 33,34 These findings suggest that skeletal muscle mass seems to be associated with OS when there is no difference in the duration of sorafenib treatment. However, the duration of sorafenib treatment might be more important for OS than skeletal muscle mass if the duration of treatment differs between patients with LSMM and non-LSMM patients.…”

“…The study indicated that presarcopenia is a significant prognostic factor in patients with two or less negative prognostic factors (serum albumin level ≤ 3.5 g/dL, AFP level ≥ 100 ng/mL, the presence of bilateral lesions, or the presence of major portal vein invasion). Regarding the association between treatment duration and survival, two previous studies have demonstrated that the duration of sorafenib treatment is an independent risk factor for survival . These findings suggest that skeletal muscle mass seems to be associated with OS when there is no difference in the duration of sorafenib treatment.…”