Purpose This phase III trial evaluated the efficacy and safety of pazopanib versus placebo in patients with locally advanced renal cell carcinoma (RCC) at high risk for relapse after nephrectomy. Patients and Methods A total of 1,538 patients with resected pT2 (high grade) or ≥ pT3, including N1, clear cell RCC were randomly assigned to pazopanib or placebo for 1 year; 403 patients received a starting dose of 800 mg or placebo. To address toxicity attrition, the 800-mg starting dose was lowered to 600 mg, and the primary end point analysis was changed to disease-free survival (DFS) for pazopanib 600 mg versus placebo (n = 1,135). Primary analysis was performed after 350 DFS events in the intent-to-treat (ITT) pazopanib 600 mg group (ITT600mg), and DFS follow-up analysis was performed 12 months later. Secondary end point analyses included DFS with ITT pazopanib 800 mg (ITT800mg) and safety. Results The primary analysis results of DFS ITT600mg favored pazopanib but did not show a significant improvement over placebo (hazard ratio [HR], 0.86; 95% CI, 0.70 to 1.06; P = .165). The secondary analysis of DFS in ITT800mg (n = 403) yielded an HR of 0.69 (95% CI, 0.51 to 0.94). Follow-up analysis in ITT600mg yielded an HR of 0.94 (95% CI, 0.77 to 1.14). Increased ALT and AST were common adverse events leading to treatment discontinuation in the pazopanib 600 mg (ALT, 16%; AST, 5%) and 800 mg (ALT, 18%; AST, 7%) groups. Conclusion The results of the primary DFS analysis of pazopanib 600 mg showed no benefit over placebo in the adjuvant setting.

Robert J Motzer and Paul Russo Memorial Sloan Kettering Cancer Center New York NY; Naomi B Haas University of Pennsylvania Philadelphia PA; Frede Donskov Aarhus University Hospital Aarhus Denmark; Marine Gross Goupil Bordeaux University Hospital Bordeaux France; Sergei Varlamov Altai Regional Cancer Center Barnaul; Evgeny Kopyltsov State Institution of Healthcare Regional Clinical Oncology Dispensary Omsk Russia; Jae Lyun Lee University of Ulsan College of Medicine; Ho Yeong Lim Sungkyunkwan University Seoul Republic of Korea; Bohuslav Melichar Palacky University Medical School and Teaching Hospital Olomouc; Milada Zemanova Charles University and General University Hospital Prague Czech Republic; Brian 1 Rini Cleveland Clinic Taussig Cancer Institute Cleveland OH; Toni K Choueiri Dana Farber Cancer Institute Boston MA; Lori A Wood Queen Elizabeth 2 Health Sciences Centre and Dalhousie University Halifax Nova Scotia; M Neil Reaume Ottawa Hospital Cancer Centre Ottawa Ontario Canada; Arnulf Stenzl University Hospital Tübingen Tübingen; Christian Doehn University of Lübeck Medical School and Urologikum Lübeck Lübeck Germany; Simon Chowdhury Guy's and St Thomas' National Health Service Foundation St Thomas' Hospital London; Ray McDermott Tallaght University Hospital and Cancer Trials Ireland Dublin; Agnieszka Michael University of Surrey Guildford United Kingdom; Weichao Bao Marlene J Carrasco Alfonso and Maurizio Voi Novartis Oncology East Hanover NJ; Paola Aimone Novartis Pharma AG Basel Switzerland; and Cora N Sternberg San Camillo Forlanini Hospital Rome Italy

J Clin Oncol. 2017 Dec 10;35(35):3895-3897. doi: 10.1200/JCO.2017.75.4242. PubMed

Eur Urol. 2018 Jul;74(1):119-121. doi: 10.1016/j.eururo.2018.01.036. PubMed

J Urol. 2018 Jun;199(6):1393-1394. doi: 10.1016/j.juro.2018.03.051. PubMed

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