Conference Coverage
Efficacy
The median OS was 5.9 months and ranged from 21 days to 60 months. There were 17 patients who survived at the 1-year follow-up, including 1 patient who survived 363 days after treatment initiation, yielding an OS rate of 40.5%. Table 2 presents 1-year survival rates with respect to select baseline data. Baseline factors found to be negligible were age, smoking, alcohol abuse, obesity, presence of HCV, medication possession ratio (MPR), prior treatment, macrovascular invasion, and AFP. Neither initial dose regimen, final dose regimen achieved, or average dose correlated with the survival rate at the 1-year follow-up.
Factors possibly associated with a higher probability of survival were baseline ECOG-PS score and baseline Child-Pugh class (Table 2). Patients with an ECOG-PS score of 0 or 1 had a higher survival rate at 1 year than did patients with an ECOG-PS score of ≥ 2 (50% vs 0%, respectively; P = .113). Patients with Child-Pugh class B or C had a lower survival rate at 1 year than did patients with Child-Pugh class A (51% vs 10%, respectively; P = .028). Other indicators were size of largest hepatic lesion ≤ 5 cm, total bilirubin ≤ 2 mg/dL, concurrent treatment, almost exclusively embolization, and treatment after sorafenib discontinuation, such as another oral chemotherapeutic agent or embolization.
The 17 patients who survived at 1 year were reviewed to see if they shared characteristics that indicated a higher probability of survival. The figure shows the baseline ECOG-PS score and the Child-Pugh class the patients who did and did not survive at the 1-year follow-up. In the first group, all patient possessed an ECOG-PS score of 0 or 1, and only 1 patient presented with Child-Pugh class B or C. In contrast, in the group who did not survive at the 1-year follow-up, there were 4 patients with ECOG-PS scores of > 1 and 9 patients who presented with Child-Pugh class B or C. The mean AFP level of this group was < 200 µg/mL, and only 4 patients were followed by Palliative Care Services. The average normalized MPR of this group was 71.9% compared with 85.3% for those who did not survive at the 1-year follow-up.
In patients who experienced at least 1 adverse event (AE), 16 survived, whereas only 1 who did not experience an AE survived (45.7% vs 14.3%, respectively; P = .210). Thirteen patients who experienced ≥ 3 AEs survived at 1 year; and only 3 patients who reported < 3 AEs survived at 1 year (61.9% vs 14.0%, respectively; P = .011). However, when the number of AEs was normalized to duration of treatment per patient, the median frequency of AEs for all patients was 0.61 AEs per month treated. The difference in survival rates grew smaller and less significant between patients who had a frequency of AEs lower than the median compared with those with a higher ratio (52.4% vs 28.6%, respectively; P = .208). Patients affected by AEs in the first 30 days and 90 days of treatment had a survival rate at the 1-year follow-up of 42.4% and 30.2%, respectively. Patients who experienced dermatologic AEs had a higher survival rate than those who did not have dermatologic AEs (60.0% vs 29.6%, respectively; P = .099). This correlation was not found with 2 other classes of AEs, gastrointestinal (50.0% vs 27.8%; P = .208) or neurologic (64.0% vs 41.2%; P = .209).
The median overall time to discontinuation was 3.4 months. The main reasons cited for discontinuing sorafenib at 1 year included symptomatic progression (52.4%), radiographic progression (23.8%), severe AEs (16.7%), and mild-to-moderate AEs (11.9%). There was overlap, as 15 patients discontinued treatment for multiple reasons. For the 22 patients who discontinued medication due to symptomatic progression at 1 year, the median time to discontinuation was 3.8 months. For the 10 patients who discontinued medication due to radiographic progression at 1 year, median time to discontinuation was 5.6 months. Seven patients (16.7%) were still on therapy at 1 year.The study considered the impact of potential dose adjustments on survival rate and safety. The authors compared patients’ prescribed dose with the recommended dose based on the package insert and monthly laboratory values if recorded. The prescribed dose was recorded as appropriate dose, below dose, above dose, or indeterminate due to the lack of current laboratory values. Patients who survived at the 1-year follow-up had a composition of 26%, 21%, 10%, and 43%, respectively. These results were similar to those of patients who did not survive at the 1-year follow-up, 29%, 12%, 30%, and 29%, respectively.