Supplementary Material for: Sunitinib for Asian Patients with Advanced Renal Cell Carcinoma: A Comparable Efficacy with Different Toxicity Profiles

Objective: We aimed to describe the efficacy and safety of sunitinib in unselected Korean advanced renal cell carcinoma (RCC) patients. Patients and Methods: From November 2005 to August 2008, 132 histologically confirmed advanced RCC patients (100 in the global expanded access program) were enrolled. Response and toxicity were assessed regularly according to the protocol. Results: Within this population, 82.6% had clear cell RCC, and 28.8% were treatment naïve. Patients received a median of 5 cycles of sunitinib (range 1–30), and the mean relative dose intensity was 82.0 ± 14.20 (SD). The progression-free survival (PFS) and overall survival rates were 8.2 and 23.1 months, respectively. For the 130 evaluable patients, the objective response rate was 34.1% (n = 45); 44.7% (n = 59) exhibited stable disease. Reasons for discontinuation were disease progression (75.0%) and toxicity (7.6%). The most frequent adverse events were thrombocytopenia (75.0%), neutropenia (70.5%), and anemia (69.7%). Low body surface area (OR = 4.2, 95% CI 1.2–13.8, p = 0.02) and previously treated status (OR = 3.1, 95% CI 1.3–7.4, p = 0.01) were highly predictive of grade 3–4 toxicities. Based on these findings, a nomogram predicting the probability of 12-month PFS was constructed, giving a concordance index of 0.675. Conclusions: Despite the different toxicity profiles, maintaining adequate dose modifications and a careful follow-up enables comparable treatment outcomes for unselected Korean advanced RCC patients.

研究目的：本研究旨在探讨舒尼替尼（sunitinib）在未经筛选的韩国晚期肾细胞癌（renal cell carcinoma, RCC）患者中的疗效与安全性。
患者与方法：2005年11月至2008年8月期间，共纳入132例经组织学确诊的晚期RCC患者（其中100例来自全球扩大准入项目）。研究按照试验方案定期评估患者的应答情况与毒性反应。
结果：该研究队列中，82.6%的患者为透明细胞RCC，28.8%的患者为初治状态。患者接受舒尼替尼治疗的中位周期数为5个（范围1~30），平均相对剂量强度为82.0±14.20（标准差）。无进展生存期（progression-free survival, PFS）与总生存期分别为8.2个月与23.1个月。在130例可评估患者中，客观缓解率为34.1%（n=45）；44.7%（n=59）的患者达到疾病稳定。停药的主要原因为疾病进展（75.0%）与毒性反应（7.6%）。最常见的不良事件为血小板减少症（75.0%）、中性粒细胞减少症（70.5%）与贫血（69.7%）。低体表面积（比值比（odds ratio, OR）=4.2，95%置信区间（confidence interval, CI）：1.2~13.8，p=0.02）与既往接受过治疗状态（OR=3.1，95%CI：1.3~7.4，p=0.01）是3~4级毒性反应的强预测因素。基于上述研究结果，我们构建了一款可预测12个月PFS概率的列线图，其一致性指数为0.675。
结论：尽管毒性谱存在差异，但通过维持恰当的剂量调整与精心的随访，可为未经筛选的韩国晚期RCC患者带来相当的治疗结局。