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 Clinicaltrials.gov as NCT01235962.

Aarhus University Hospital Aarhus Denmark

Altai Regional Cancer Center Barnaul Russia

Bordeaux University Hospital Bordeaux France

Charles University and General University Hospital Prague Czech Republic

Cleveland Clinic Taussig Cancer Institute Cleveland OH USA

Dana Farber Cancer Institute Boston MA USA

Englander Institute for Precision Medicine Weill Cornell Medicine New York NY USA

Guy's and St Thomas' National Health Service Foundation St Thomas' Hospital London UK

Memorial Sloan Kettering Cancer Center New York NY USA

Novartis Oncology East Hanover NJ USA

Novartis Pharma AG Basel Switzerland

Palacky University Medical School and Teaching Hospital Olomouc Czech Republic

Queen Elizabeth 2 Health Sciences Centre and Dalhousie University Halifax NS Canada

State Institution of Healthcare Regional Clinical Oncology Dispensary Omsk Russia

Sungkyunkwan University Seoul South Korea

Tallaght University Hospital and Cancer Trials Ireland Dublin Ireland

The Ottawa Hospital Cancer Centre Ottawa ON Canada

University Hospital Tubingen Tubingen Germany

University of Lubeck Medical School and Urologikum Lubeck Lubeck Germany

University of Pennsylvania Philadelphia PA USA

University of Surrey Guildford UK

University of Ulsan College of Medicine Seoul South Korea

Eur Urol. 2021 Jul;80(1):e33-e34. doi: 10.1016/j.eururo.2021.04.025. PubMed

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ClinicalTrials.gov
NCT01235962