Adjuvant Pazopanib Versus Placebo After Nephrectomy in Patients With Localized or Locally Advanced Renal Cell Carcinoma: Final Overall Survival Analysis of the Phase 3 PROTECT Trial.

Most studies indicate no benefit of adjuvant therapy with VEGFR tyrosine kinase inhibitors in advanced renal cell carcinoma (RCC). PROTECT (NCT01235962) was a randomized, double-blind, placebo-controlled phase 3 study to evaluate adjuvant pazopanib in patients with locally advanced RCC at high risk of relapse after nephrectomy (pazopanib, n = 769; placebo, n = 769). The results of the primary analysis showed no difference in disease-free survival between pazopanib 600 mg and placebo. Here we report the final overall survival (OS) analysis (median follow-up: pazopanib, 76 mo, interquartile range [IQR] 66-84; placebo, 77 mo, IQR 69-85). There was no significant difference in OS between the pazopanib and placebo arms (hazard ratio 1.0, 95% confidence interval 0.80-1.26; nominal p > 0.9). OS was worse for patients with T4 disease compared to those with less advanced disease and was better for patients with body mass index (BMI) ≥30 kg/m2 compared to those with lower BMI. OS was significantly better for patients who remained diseasefree at 2 yr after treatment compared with those who relapsed within 2 yr. These findings are consistent with the primary outcomes from PROTECT, indicating that adjuvant pazopanib does not confer a benefit in terms of OS for patients following resection of locally advanced RCC. PATIENT SUMMARY: In the randomized, double-blind, placebo-controlled phase 3 PROTECT study, overall survival was similar for patients with locally advanced renal cell carcinoma (RCC) at high risk of relapse after nephrectomy who received adjuvant therapy with pazopanib or placebo. Pazopanib is not recommended as adjuvant therapy following resection of locally advanced RCC. This trial is registered at as NCT01235962.

European urology. 2021 Jan 15 [Epub ahead of print]

Robert J Motzer, Paul Russo, Naomi Haas, Christian Doehn, Frede Donskov, Marine Gross-Goupil, Sergei Varlamov, Evgeny Kopyltsov, Jae Lyun Lee, Ho Yeong Lim, Bohuslav Melichar, Milada Zemanova, Brian Rini, Toni K Choueiri, Lori Wood, M Neil Reaume, Arnulf Stenzl, Simon Chowdhury, Ray McDermott, Agnieszka Michael, Miguel Izquierdo, Paola Aimone, Hong Zhang, Cora N Sternberg, PROTECT study investigators

Memorial Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: ., Memorial Sloan Kettering Cancer Center, New York, NY, USA., University of Pennsylvania, Philadelphia, PA, USA., University of Lubeck Medical School and Urologikum Lubeck, Lubeck, Germany., Aarhus University Hospital, Aarhus, Denmark., Bordeaux University Hospital, Bordeaux, France., Altai Regional Cancer Center, Barnaul, Russia., State Institution of Healthcare Regional Clinical Oncology Dispensary, Omsk, Russia., University of Ulsan College of Medicine, Seoul, South Korea., Sungkyunkwan University, Seoul, South Korea., Palacky University Medical School and Teaching Hospital, Olomouc, Czech Republic., Charles University and General University Hospital, Prague, Czech Republic., Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA., Dana-Farber Cancer Institute, Boston, MA, USA., Queen Elizabeth II Health Sciences Centre and Dalhousie University, Halifax, NS, Canada., The Ottawa Hospital Cancer Centre, Ottawa, ON, Canada., University Hospital Tubingen, Tubingen, Germany., Guy's and St Thomas' National Health Service Foundation, St. Thomas' Hospital, London, UK., Tallaght University Hospital and Cancer Trials Ireland, Dublin, Ireland., University of Surrey, Guildford, UK., Novartis Oncology, East Hanover, NJ, USA., Novartis Pharma AG, Basel, Switzerland., Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY, USA.