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.
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
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.
|Immediate CN N = 50||Deferred CN N = 49|
|Median age (years)||60.0||58.0|
|WHO PS 0:/1:||72.0%/28.0%||63.3%/36.7%|
|MSKCC intermediate risk||86.0%||87.7%|
|≥ 2 measurable metastatic sites||86.0%||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 performed||N = 46||N = 40|
|Progression 4 weeks after CN||19.6%||23.5%|
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
Legal entity responsible for the study
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.