A randomized, double-blind phase III study of pazopanib in treatment-naive and cytokine-pretreated patients with advanced renal cell carcinoma (RCC)
Authors: Sternberg C. N. , Szczylik C. , Lee E. , Salman P. V. , Mardiak J. , Davis I. D. , Pandite L. , Chen M. , McCann L. , Hawkins R. 
Published: August 2020

5021^

Background: Pazopanib, an oral multikinase angiogenesis inhibitor, has shown clinical efficacy in patients (pts) with advanced RCC. In this study (VEG105192), the efficacy and safety of pazopanib was compared with placebo in advanced RCC. Methods: Pts (N = 400 planned) with clear cell advanced RCC and measurable disease with no prior treatment or 1 prior cytokine-based treatment, were stratified and randomized (2:1) to pazopanib 800 mg QD or placebo. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), response rate (RR), and safety. The study had ≥ 90% power to detect an 80% improvement in PFS and a 50% improvement in OS, by stratified log-rank tests with α = 0.025 one-sided. Pts received continuous treatment until disease progression (PD), death or unacceptable toxicity. Upon PD, placebo pts could receive pazopanib via an extension study. Final PFS, RR and safety results are reported here. Results: A total of 233 treatment-naïve and 202 cytokine-pretreated pts were enrolled (290 pazopanib; 145 placebo). Pt characteristics were balanced between the 2 arms. ECOG 0/1 was 42%/58% and 41%/59% for pazopanib and placebo pts, respectively. PFS was significantly prolonged with pazopanib in the overall study population (9.2 vs 4.2 mos; HR: 0.46; 95% CI: 0.34, 0.62; p < 0.0000001), in treatment naïve pts (11.1 vs 2.8 mos; HR: 0.40; 95% CI: 0.27, 0.60; p < 0.0000001), and in cytokine-pretreated pts (7.4 vs 4.2 mos; HR: 0.54; 95% CI: 0.35, 0.84; p < 0.001). RR was 30% with pazopanib (vs 3% with placebo) and median duration of response was 58.7 wks. Median duration of exposure was 7.4 mos (pazopanib) and 3.8 mos (placebo). The majority of adverse events (AEs) were grade 1 or 2. Most common AEs in pazopanib-treated pts were diarrhea (52%; 4% Gr 3/4), hypertension (40%; 4% Gr 3/4), hair color change (38%; <1% Gr 3/4), nausea (26%; <1% Gr 3/4), anorexia (22%; 2% Gr 3/4), and vomiting (21%; 2% Gr 3/4). The most common laboratory abnormality was ALT elevation (53%; 10% Gr 3; 2% Gr 4). Conclusions: Pazopanib monotherapy was well tolerated and demonstrated a significant improvement in PFS and RR compared to placebo. Final OS results are awaited.

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