Randomized Phase III Trial of Adjuvant Pazopanib Versus Placebo After Nephrectomy in Patients With Localized or Locally Advanced Renal Cell Carcinoma

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.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2017 Sep 13 [Epub ahead of print]

Robert J Motzer, Naomi B Haas, Frede Donskov, Marine Gross-Goupil, Sergei Varlamov, Evgeny Kopyltsov, Jae Lyun Lee, Bohuslav Melichar, Brian I Rini, Toni K Choueiri, Milada Zemanova, Lori A Wood, M Neil Reaume, Arnulf Stenzl, Simon Chowdhury, Ho Yeong Lim, Ray McDermott, Agnieszka Michael, Weichao Bao, Marlene J Carrasco-Alfonso, Paola Aimone, Maurizio Voi, Christian Doehn, Paul Russo, Cora N Sternberg, PROTECT investigators

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 I. Rini, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; Toni K. Choueiri, Dana-Farber Cancer Institute, Boston, MA; Lori A. Wood, Queen Elizabeth II 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.

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