Long-Term Survival in Patients With Relapsed/Refractory Advanced Renal Cell Carcinoma Treated With Tivozanib: Analysis of the Phase III TIVO-3 Trial.

BACKGROUND: Tivozanib is an oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) with efficacy in advanced renal cell carcinoma (RCC). Long-term exploratory analyses from the TIVO-3 trial in relapsed/refractory (R/R) RCC including patients (26%) with prior immuno-oncology (IO) therapy are reported. METHODS: Patients with R/R advanced RCC that progressed with 2 or 3 prior systemic therapies (≥1 VEGFR TKI) were randomized to tivozanib 1.5 mg QD or sorafenib 400 mg BID, stratified by IMDC risk and previous therapy. Safety, investigator-assessed long-term progression-free survival (LT-PFS), and serial overall survival (OS) were assessed. RESULTS: Mean time on treatment was 11.0 months with tivozanib (n = 175) and 6.3 months with sorafenib (n = 175). Fewer grade ≥3 treatment-related adverse events occurred with tivozanib (46%) than sorafenib (55%). Dose modification rates were lower with tivozanib than sorafenib across age/prior IO subgroups; prior IO therapy did not impact dose reductions or discontinuations in either arm. Landmark LT-PFS rates were higher with tivozanib (3 years: 12.3% vs 2.4%; 4 years: 7.6% vs 0%). After 22.8 months mean follow-up, the OS HR was 0.89 (95% CI, 0.70-1.14); when conditioned on 12-month landmark PFS, tivozanib showed significant OS improvement over sorafenib (HR, 0.45; 95% CI, 0.22-0.91; 2-sided P = .0221). CONCLUSIONS: Tivozanib demonstrated a consistent safety profile and long-term survival benefit in patients with R/R advanced RCC who were alive and progression free at 12 months. These post hoc exploratory analyses of LT-PFS and conditional OS support a clinically meaningful improvement with tivozanib versus sorafenib in this advanced RCC population.

Cost of care for malignant and benign renal masses.

BACKGROUND: Limitations of current diagnotic techniques may allow some patients with presumed renal cell carcinoma (RCC) to undergo nephrectomy without definitive confirmation of malignancy. OBJECTIVES: To confirm previous estimates of postnephrectomy renal mass diagnosis and to assess the economic impact of nephrectomy. METHODS: This retrospective cohort analysis identified commercial enrollees who underwent nephrectomy with a diagnosis of RCC between July 1, 2000, and March 30, 2008. Study subjects were stratified based on medical claims for benign or malignant disease after the nephrectomy date. Cohorts were compared on resource utilization before and after nephrectomy, occurrence of postsurgical complications, and associated 1-year costs of care. RESULTS: Of 10,404 patients undergoing nephrectomy for presumed RCC, 1613 (15.5%) were subsequently identified as having benign disease, despite median presurgical diagnostic expenditures of $1311 per patient (interquartile range [IQR], $467-$2606). Median expenditures for the 12 months postnephrectomy were $26,920 per patient (IQR, $16,851-$46,982) for those with malignant disease and $23,951 per patient (IQR, $14,873-$38,190) for those with benign disease (P<.0001). For patients with benign disease, 17.5% experienced a postsurgical adverse event, resulting in a 1.5-fold increase in expenditures (median $31,838 per patient for those with event vs $22,770 per patient for those without event; P<.0001). CONCLUSIONS: In this study, approximately 1 in 6 patients were found to have a benign renal mass postnephrectomy. Given the risk of surgical complications and related economic consequences, methods for better identifying malignant versus benign disease prior to surgery could provide significant benefits to patients and payers.