Portal de Periódicos da CAPES

Immediate versus deferred cytoreductive nephrectomy (CN) in patients with synchronous metastatic renal cell carcinoma (mRCC) receiving sunitinib (EORTC 30073 SURTIME)

2017; Elsevier BV; Volume: 28; Linguagem: Inglês

10.1093/annonc/mdx440.030

1569-8041

Axel Bex, Peter F.A. Mulders, Michael A.S. Jewett, John Wagstaff, R. Van Velthoven, P.M. Laguna Pes, Lori Wood, Harm H.E. van Melick, Patricia M.M.B. Soetekouw, Jean-Baptiste Lattouf, Thomas Powles, Ekaterini Boleti, Igle J. de Jong, Sylvie Rottey, Bertrand Tombal, Sandrine Marréaud, Laurence Collette, Sandra Collette, Christian U. Blank, John B.A.G. Haanen,

Pancreatic and Hepatic Oncology Research

Background: In clinical practice, mRCC patients with the primary tumour in situ are offered CN followed by targeted therapy. This randomized trial explored a period of targeted therapy (sunitinib) prior to CN as an alternative approach. Methods: Patients with mRCC were randomized 1:1 to immediate CN followed by sunitinib versus 3 cycles sunitinib followed by CN and sunitinib. Inclusion required histologically confirmed clear-cell subtype, resectable asymptomatic primary tumour and < = 3 surgical risk factors (Culp et al., Cancer 2010). To detect a 3 months increase in median progression free survival (Hazard ratio [HR] = 0.75) with deferred CN with a 2-sided 5% logrank test at 80% power, 380 events were needed. Due to poor accrual, the IDMC recommended to report the progression free rate (PFR) at week 28 instead (98 patients needed). Overall survival (OS), adverse events and post-operative progression in both arms were secondary endpoints.Table: LBA35Immediate CN N = 50Deferred CN N = 49Median age (years)60.058.0Male:/Female:82.0%/18.0%79.6%/20.4%WHO PS 0:/1:72.0%/28.0%63.3%/36.7%MSKCC intermediate risk86.0%87.7%≥ 2 measurable metastatic sites86.0%93.9%Mean (SD) primary tumor size (mm)93.1 (37.8)96.8 (31.3)Progression at week 16* (*before planned CN in the deferred arm)46%32.7%*CN performedN = 46N = 40Surgical complications43.5%27.5%Progression 4 weeks after CN19.6%23.5% Open table in a new tab Results: The study closed after 5.7 years with 99 patients entered by 19 institutions. As of May 5, 2017, median follow-up is 3.3 years. In the immediate CN arm, 46 of 50 patients had CN, 40 of 46 had post-CN sunitinib. In the deferred CN arm, 48 of 49 patients had sunitinib, 40 of 48 had CN and 26 of 40 had post-CN sunitinib (Table). PFR was 42.0% (CI: 28.2 – 56.8) and 42.9% (28.8 – 57.8) in the immediate and deferred arms, resp (p > 0.99). The OS HR (stratified by WHO PS) of intention to treat (ITT) with deferred versus immediate CN in all patients was 0.57 (CI: 0.34 – 0.95, p = 0.032) with a median OS of 32.4 (14.5-65.3) and 15.1 months (CI: 9.3, 29.5), respectively. Conclusions: The sequence of CN and sunitinib did not affect the PFR at 28 weeks. The sample size precludes definitive conclusions from other endpoints, although an OS signal was seen for deferred CN. CN after sunitinib appears safe. Clinical trial identification: NCT01099423 Legal entity responsible for the study: EORTC Funding: Pfizer Disclosure: A. Bex: Participation in Advisory boards of Pfizer, BMS, Roche, Eisai and Ipsen. M.A.S. Jewett: Honorarium: Ipsen, Pfizer. Consultant: Pfizer, Theralase Therapeutics Inc. Ownership: Stock Theralase Therapeutics Inc. J. Wagstaff: Advisory boards for Pfizer. T. Powles: Research funds: Pfizer, Novartis, Roche, AZ. Honoraria: Pfizer, Novartis, Roche, BMS, MSD, Ipsen, Eisei.E. Boleti: Advisory board for Pfizer, Eisai, Ipsen. S. Rottey: Speaker fee from BMS, Pfizer, Roche, Bayer. C.U. Blank: Advisory board for Pfizer, BMS and Roche. J.B. Haanen: Advisory role for Pfizer. All other authors have declared no conflicts of interest.