ASCO2013：一线治疗之索拉非尼上市后的临床监测

尽管索拉非尼被FDA批准用于晚期肝癌患者，而不管患者的肝功能分级，但索拉非尼的两个3期临床试验都是基于ChildA级的患者，将它用于肝功能较差的ChildB级患者，临床医生总会有所顾虑。这个叫做GIDEON的前瞻性临床研究，收集了全球超过3,000名的索拉非尼治疗患者的数据。整体而言，副作用和药物引起的副作用在不同Child分级患者中相似。其中，ChildB级的患者接受的平均治疗剂量稍大，而ChildA级患者接受治疗的疗程更长。ChildA级和B级患者的中位生存时间分别为4.7月（95%CI：4.3-5.2）和4.4月（95%CI：3.5-5.5）。对于ChildB级的患者，评分越高，预后越差：7分、8分和9分的患者的中位生存时间分别是：6.2月（95%CI：4.9-8.7）、4.8月（95%CI：4.1-6.9）和3.7月（95%CI：3.0-5.1）。

摘要详情：

Abstract:

Background: GIDEON is a prospective, non-interventional study. Completion of GIDEON creates a large, global database of >3000 Sor-treated unresectable HCC (uHCC) pts, allowing for evaluation of a broad pt population, including Child-Pugh (CP) B pts with more advanced liver dysfunction.

Methods: Baseline characteristics were collected in pts for whom a decision to treat with Sor had been made in clinical practice. Adverse events (AEs), dosing, and outcomes data were collected during follow-up.

Results: 3,202 pts were evaluable for safety. Overall, the incidence of AEs and drug-related (DR) AEs was similar across CP subgroups, although serious AEs (SAEs) were more common in CP-B than CP-A pts. The rate of DR AEs (event per patient-year) was also comparable between CP-A and CP-B pts. The average daily Sor dose was slightly higher in CP-B than CP-A pts; duration of treatment was longer in CP-A (Table). In the intent-to-treat population (n=3,213), median overall survival (OS) (months [95% CI]) was longer in CP-A (13.6 [12.8-14.7]) than CP-B pts (5.2 [4.6-6.3]); time to progression was similar: CP-A (4.7 [4.3-5.2]); CP-B (4.4 [3.5-5.5]). Median OS was shorter in pts with a higher CP-B score: 7 (6.2 [4.9-8.7]); 8 (4.8 [4.1-6.9]); 9 (3.7 [3.0-5.1]).

Conclusions: Sor safety and dosing during treatment are generally consistent across pts irrespective of liver function. As anticipated, CP status is a strong prognostic factor for OS in uHCC pts.