A randomized, double-blind phase III study of pazopanib in treatment-naive and cytokine-pretreated patients with advanced renal cell carcinoma (RCC).

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. [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519-521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco. org/conflictofinterest .