Everolimus in metastatic renal cell carcinoma (mRCC): Subgroup analysis of patients (pts) with one versus two prior vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) therapies enrolled in the phase III RECORD-1 study.

Abstract

304 Background: The mammalian target of rapamycin (mTOR) inhibitor everolimus is the only medication to have shown efficacy in a randomized, controlled, phase III clinical trial (RECORD-1) in pts with mRCC after progression on VEGFR-TKIs. Everolimus more than doubled progression-free survival (PFS) vs. placebo (4.9 vs 1.9 months) and reduced the risk of disease progression by 67%. This analysis evaluated the effect of everolimus on survival in pts who had received 1 vs 2 prior VEGFR-TKIs. Methods: Pts with mRCC who progressed on sunitinib (SU) and/or sorafenib (SOR) were randomized (2:1) to receive everolimus 10 mg/day (n = 277) or placebo (n = 139) plus best supportive care in the double- blind, phase III RECORD-1 study (ClinicalTrials.gov: NCT00410124 ). Results: Before enrollment, the majority of pts received only 1 VEGFR- TKI (317 pts, 74%), with 317 pts receiving either SU or SOR (everolimus = 211; placebo = 106) and 99 pts receiving both SU and SOR (everolimus = 66; placebo = 33). Median PFS was 5.42 mo (95% confidence interval [CI]: 4.30, 5.82) in pts receiving everolimus who had received 1 prior VEGFR-TKI and 1.87 mo (95% CI: 1.84, 2.14) in those receiving placebo (hazard ratio [HR]: 0.31; 95% CI: 0.23, 0.42; p < .001). Median PFS was 3.78 mo (95% CI: 3.25, 5.13) for the everolimus group in pts who received 2 prior VEGFR-TKIs, versus 1.87 mo (95% CI: 1.77, 3.06) for the placebo group (HR: 0.37; 95% CI: 0.22, 0.63; p < 0.001). Conclusions: Pts in all stratified subgroups derived significant clinical benefit from everolimus treatment, including pts previously treated with either 1 or 2 VEGFR-TKIs. However, there was a trend toward a longer PFS in pts treated with 1 prior VEGFR-TKI compared with 2 VEGFR-TKIs. [Table: see text]