Background

Adjuvant sunitinib significantly improved disease-free survival (DFS) versus placebo in patients with locoregional renal cell carcinoma (RCC) at high risk of recurrence after nephrectomy (hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.59–0.98; p = 0.03).

Objective

To report the relationship between baseline factors and DFS, pattern of recurrence, and updated overall survival (OS).

Design, setting, and participants

Data for 615 patients randomized to sunitinib (n = 309) or placebo (n = 306) in the S-TRAC trial.

Outcome measurements and statistical analysis

Subgroup DFS analyses by baseline risk factors were conducted using a Cox proportional hazards model. Baseline risk factors included: modified University of California Los Angeles integrated staging system criteria, age, gender, Eastern Cooperative Oncology Group performance status (ECOG PS), weight, neutrophil-to-lymphocyte ratio (NLR), and Fuhrman grade.

Results and limitations

Of 615 patients, 97 and 122 in the sunitinib and placebo arms developed metastatic disease, with the most common sites of distant recurrence being lung (40 and 49), lymph node (21 and 26), and liver (11 and 14), respectively. A benefit of adjuvant sunitinib over placebo was observed across subgroups, including: higher risk (T3, no or undetermined nodal involvement, Fuhrman grade ≥2, ECOG PS ≥1, T4 and/or nodal involvement; hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.55–0.99; p = 0.04), NLR ≤3 (HR 0.72, 95% CI 0.54–0.95; p = 0.02), and Fuhrman grade 3/4 (HR 0.73, 95% CI 0.55–0.98; p = 0.04). All subgroup analyses were exploratory, and no adjustments for multiplicity were made. Median OS was not reached in either arm (HR 0.92, 95% CI 0.66–1.28; p = 0.6); 67 and 74 patients died in the sunitinib and placebo arms, respectively.

Conclusions

A benefit of adjuvant sunitinib over placebo was observed across subgroups. The results are consistent with the primary analysis, which showed a benefit for adjuvant sunitinib in patients at high risk of recurrent RCC after nephrectomy.

Patient summary

Most subgroups of patients at high risk of recurrent renal cell carcinoma after nephrectomy experienced a clinical benefit with adjuvant sunitinib.

Trial registration

ClinicalTrials.gov NCT00375674.

中文翻译：

---

肾切除术后高危肾细胞癌的佐尼替尼辅助治疗：亚组分析和更新的总体生存结果

背景

与安慰剂相比，肾局部切除术后复发高局部区域肾细胞癌（RCC）患者，舒尼替尼辅助治疗显着改善了无病生存期（DFS）（危险比[HR] 0.76，95％置信区间[CI] 0.59-0.98；p  = 0.03）。

客观的

报告基线因素与DFS，复发模式和更新的总生存期（OS）之间的关系。

设计，设置和参与者

 在S-TRAC试验中，随机分配给舒尼替尼（n  = 309）或安慰剂（n = 306）的615位患者的数据。

成果测量和统计分析

使用Cox比例风险模型按基线危险因素进行亚组DFS分析。基线危险因素包括：修改后的加利福尼亚大学洛杉矶分校综合分期系统标准，年龄，性别，东部合作肿瘤小组表现状态（ECOG PS），体重，中性白细胞与淋巴细胞之比（NLR）和Fuhrman评分。

结果与局限性

在615例患者中，舒尼替尼和安慰剂组中有97例和122例发生转移性疾病，最常见的远处复发部位分别是肺（40和49），淋巴结（21和26）和肝（11和14）。 。在各亚组中观察到舒尼替尼比安慰剂有益处，包括：较高的风险（T3，无或不确定的淋巴结受累，Fuhrman≥2，ECOG PS≥1，T4和/或淋巴结受累；危险比[HR] 0.74，95置信区间百分比[CI] 0.55–0.99；p  = 0.04），NLR≤3（HR 0.72、95％CI 0.54–0.95；p  = 0.02）和菲尔曼等级3/4（HR 0.73、95％CI 0.55–0.98 ） ；p  = 0.04）。所有亚组分析均为探索性，未对多重性进行任何调整。两组均未达到OS的中位数（HR 0.92，95％CI 0.66-1.28；p  = 0.6）；舒尼替尼组和安慰剂组分别死亡67例和74例。

结论

在各亚组中均观察到舒尼替尼作为辅助药物优于安慰剂。结果与初步分析一致，该分析表明肾切除术后复发性RCC高风险患者可使用舒尼替尼作为辅助治疗。

病人总结

肾切除术后复发性肾细胞癌高风险的大多数患者亚组都在使用舒尼替尼辅助治疗后获得了临床益处。

试用注册

ClinicalTrials.gov NCT00375674。