Department of Medical Oncology, Duke Cancer Center, Durham, North Carolina.
Global Product Development, Pfizer Inc, La Jolla, California.
Clin Cancer Res. 2019 Feb 15;25(4):1165-1173. doi: 10.1158/1078-0432.CCR-18-1724. Epub 2018 Nov 6.
In the S-TRAC trial, adjuvant sunitinib prolonged disease-free survival (DFS) versus placebo in patients with loco-regional renal cell carcinoma at high risk of recurrence after nephrectomy. An exploratory analysis evaluated associations between SNPs in several angiogenesis- or hypoxia-related genes and clinical outcomes in S-TRAC.
Blood samples were genotyped for 10 SNPs and one insertion/deletion mutation using TaqMan assays. DFS was compared using log-rank tests for each genotype in sunitinib versus placebo groups and between genotypes within each of three (sunitinib, placebo, and combined sunitinib plus placebo) treatment groups. values were unadjusted.
In all, 286 patients (sunitinib, = 142; placebo, = 144) were genotyped. Longer DFS [HR; 95% confidence interval (CI)] was observed with sunitinib versus placebo for C/C (HR 0.44; 95% CI, 0.21-0.91; = 0.023), T/T (HR 0.46; 95% CI, 0.23-0.90; = 0.020), and T/T (HR 0.53; 95% CI, 0.30-0.94; = 0.028). Shorter DFS was observed for C/A versus C/C with sunitinib, placebo, and combined therapies ( ≤ 0.05), and A/A versus C/C with sunitinib ( = 0.022). A/C versus A/A was associated with shorter DFS in the placebo ( = 0.038) and combined ( = 0.006) groups.
Correlations between and SNPs and longer DFS with sunitinib suggest germline SNPs are predictive of improved outcomes with adjuvant sunitinib in patients with renal cell carcinoma. Independent validation studies are needed to confirm these findings.
在 S-TRAC 试验中，辅助舒尼替尼可延长肾细胞癌患者肾切除术高复发风险后的无病生存（DFS），与安慰剂相比。一项探索性分析评估了 S-TRAC 中几种血管生成或缺氧相关基因的 SNP 与临床结局之间的关联。
采用 TaqMan 检测法对 10 个 SNP 和一个插入/缺失突变进行血液样本基因分型。在舒尼替尼与安慰剂组之间以及在每个（舒尼替尼、安慰剂和舒尼替尼加安慰剂联合）治疗组内的三种基因型之间，使用对数秩检验比较每个基因型的 DFS。值未经调整。
共对 286 例患者（舒尼替尼，n = 142；安慰剂，n = 144）进行了基因分型。与安慰剂相比，舒尼替尼治疗的患者 DFS 更长[HR；95%置信区间（CI）]： C/C（HR 0.44；95%CI，0.21-0.91； = 0.023）， T/T（HR 0.46；95%CI，0.23-0.90； = 0.020），和 T/T（HR 0.53；95%CI，0.30-0.94； = 0.028）。与舒尼替尼、安慰剂和联合治疗相比， C/A 与 C/C 相比 DFS 更短（ ≤ 0.05），与舒尼替尼相比，A/A 与 C/C 相比 DFS 更短（ = 0.022）。与安慰剂（ = 0.038）和联合治疗（ = 0.006）相比， A/C 与 A/A 与 DFS 更短相关。
与 和 SNPs 相关的相关性以及舒尼替尼治疗的 DFS 延长表明，生殖系 SNPs 可预测肾细胞癌患者接受辅助舒尼替尼治疗的结局改善。需要进行独立的验证研究来证实这些发现。
