Adjuvant Sunitinib for High-risk Renal Cell Carcinoma After Nephrectomy: Subgroup Analyses and Updated Overall Survival Results

被引：175

作者：

Motzer, Robert J. ^{[1
]}

Ravaud, Alain ^{[2
]}

Patard, Jean-Jacques ^{[3
]}

Pandha, Hardev S. ^{[4
,5
]}

George, Daniel J. ^{[6
]}

Patel, Anup ^{[7
]}

Chang, Yen-Hwa ^{[8
]}

Escudier, Bernard ^{[9
]}

Donskov, Frede ^{[10
]}

Magheli, Ahmed ^{[11
]}

Carteni, Giacomo ^{[12
,13
]}

Laguerre, Brigitte ^{[14
]}

Tomczak, Piotr ^{[15
]}

Breza, Jan ^{[16
]}

Gerletti, Paola ^{[17
]}

Lechuga, Mariajose ^{[17
]}

Lin, Xun ^{[18
]}

Casey, Michelle ^{[19
]}

Serfass, Lucile ^{[20
]}

Pantuck, Allan J. ^{[21
]}

Staehler, Michael ^{[22
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Oncol, 1275 York Ave, New York, NY 10065 USA

[2] Bordeaux Univ Hosp, Dept Med Oncol, Bordeaux, France

[3] Ctr Hosp Mt De Marsan, Mt De Marsan, France

[4] Univ Surrey, Dept Clin & Expt Med, Guildford, Surrey, England

[5] Univ Surrey, Dept Microbial Sci, Guildford, Surrey, England

[6] Duke Canc Ctr, Div Oncol, Durham, NC USA

[7] Spire Roding Hosp, London, England

[8] Taipei Vet Gen Hosp, Dept Urol, Taipei, Taiwan

[9] Inst Gustave Roussy, Dept Med Oncol, Villejuif, France

[10] Aarhus Univ Hosp, Dept Oncol, Aarhus, Denmark

[11] Charite, Dept Urol, Berlin, Germany

[12] Azienda Osped Rilievo Nazl A Cardarelli, Div Oncol, Naples, Italy

[13] Azienda Osped Rilievo Nazl A Cardarelli, Div Urol, Naples, Italy

[14] Ctr Eugene Marquis, Med Oncol, Rennes, France

[15] Klin Onkol Oddzial Chemioterapii, Poznan, Poland

[16] Slovak Med Univ Bratislava, Dept Urol, Bratislava, Slovakia

[17] Pfizer SrL, Milan, Italy

[18] Pfizer Inc, La Jolla, CA USA

[19] Pfizer Inc, Collegeville, PA USA

[20] Pfizer Oncol, Paris, France

[21] Ronald Reagan UCLA Med Ctr, Dept Urol, Los Angeles, CA USA

[22] Univ Hosp Munich, Dept Urol, Munich, Germany

来源：

EUROPEAN UROLOGY | 2018年 / 73卷 / 01期

关键词：

Adjuvant; Disease-free survival; Renal cell carcinoma; Sunitinib; GASTROINTESTINAL STROMAL TUMOR; EXPANDED-ACCESS TRIAL; STAGE-III MELANOMA; RANDOMIZED-TRIAL; DOUBLE-BLIND; PHASE-3; TRIAL; COLON-CANCER; IMATINIB; PLACEBO; FLUOROURACIL;

D O I：

10.1016/j.eururo.2017.09.008

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

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. (c) 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

引用

页码：62 / 68

页数：7

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