Robert J Motzer1, Alain Ravaud2, Jean-Jacques Patard3, Hardev S Pandha4, Daniel J George5, Anup Patel6, Yen-Hwa Chang7, Bernard Escudier8, Frede Donskov9, Ahmed Magheli10, Giacomo Carteni11, Brigitte Laguerre12, Piotr Tomczak13, Jan Breza14, Paola Gerletti15, Mariajose Lechuga15, Xun Lin16, Michelle Casey17, Lucile Serfass18, Allan J Pantuck19, Michael Staehler20. 1. Department of Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: motzerr@mskcc.org. 2. Department of Medical Oncology, Bordeaux University Hospital, Bordeaux, France. 3. Centre Hospitalier De Mont De Marsan, Mont-de-Marsan, France. 4. Department of Clinical and Experimental Medicine and Department of Microbial Sciences, University of Surrey, Guildford, UK. 5. Division of Oncology, Duke Cancer Center, Durham, NC, USA. 6. Spire Roding Hospital, London, UK. 7. Department of Urology, Taipei Veterans General Hospital, Taipei, Taiwan. 8. Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France. 9. Department of Oncology, Aarhus University Hospital, Aarhus, Denmark. 10. Department of Urology, Charité Universitaetsmedizin Berlin, Berlin, Germany. 11. Division of Oncology and Division of Urology, Azienda Ospedaliera di Rilievo Nazionale A. Cardarelli, Naples, Italy. 12. Medical Oncology, Centre Eugene Marquis, Rennes, France. 13. Klinika Onkologii Oddzial Chemioterapii, Poznan, Poland. 14. Department of Urology, Slovak Medical University in Bratislava, Bratislava, Slovakia. 15. Pfizer S.r.L, Milan, Italy. 16. Pfizer Inc., La Jolla, CA, USA. 17. Pfizer Inc., Collegeville, PA, USA. 18. Pfizer Oncology, Paris, France. 19. Department of Urology, Ronald Reagan UCLA Medical Center, Los Angeles, CA, USA. 20. Department of Urology, University Hospital of Munich, Munich, Germany.
Abstract
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) orplacebo (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 thesunitinib 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.
RCT Entities:
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.
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