SWITCH: A randomized sequential open-label study to evaluate efficacy and safety of sorafenib (SO)/sunitinib (SU) versus SU/SO in the treatment of metastatic renal cell cancer (mRCC).

Abstract

393 Background: The sequential use of SO and SU has been investigated retrospectively in patients with mRCC. We report here results from the first randomized study to prospectively compare SO/SU versus SU/SO. Methods: Pts with mRCC unsuitable for cytokines without prior systemic therapy, ECOG PS 0/1, MSKCC score low or intermediate, and ≥1 measurable lesion were randomized to receive open-label SO/SU (arm A) or SU/SO (arm B) in standard dosage. Primary endpoint: total PFS (T-PFS) from randomization to event during 2nd line therapy. Therapy continued until progression or intolerability. The study was powered to detect a 47% increase in T-PFS with SO/SU compared to SU/SO using log-rank testing and Cox proportional hazard regression model. ( NCT00732914 ). Results: A total of 365 pts were enrolled: 182 arm A, 183 arm B.The two arms were well balanced: median age (A/B): 64/65 yrs; prior nephrectomy: 74/65%; MSKCC intermediate: 59/51%, low: 39/45%; clear cell histology: 90/84%. At time of final T-PFS analysis 220 events had occurred (A, n=117 [64%]; B, n=103 [56%]). There was no statistically significant difference in T-PFS across arms: HR 1.01, p=0.54, arm A and arm B, respectively. Likewise, there was no statistically significant difference in OS: HR 0.997, p=0.49, nor in the first PFS across arms: HR 1.19, p=0.92. Fewer pts crossed over to receive SO in arm B (n=76) than to receive SU in arm A (n=103). Overall DCR was 72/67%. There was a marked difference in AEs leading to permanent discontinuation between the two groups (18.6/29.5%). Most frequent (>20%) side effects under 1st-line treatment SO vs SU were alopecia (29/4%), diarrhea (43/29%), dysgeusia (8/21%), fatigue (21/34%), HFSR (37/20%), hypertension (24/24%), nausea (18/24%) and rash (22/3%). AEs were generally lower during 2nd-line therapy. Conclusions: There was no significant difference in T-PFS, OS, DCR and 1st-line PFS between the two sequential treatments. Both drugs provided overall benefit regardless of sequence. Side effect profiles differ, but were generally less frequent during 2nd-line therapy. More patients reached 2nd-line in the SO/SU arm. Clinical trial information: NCT00732914.