Randomized phase III trial of adjuvant pazopanib versus placebo after nephrectomy in patients with locally advanced renal cell carcinoma (RCC) (PROTECT).

Abstract

4507 Background: PROTECT (NCT01235962) evaluated the efficacy and safety of pazopanib (PAZ) versus placebo in patients (pts) with locally advanced renal cell carcinoma (RCC) post nephrectomy. Methods: 1538 pts with resected pT2 (high grade), pT3 or greater clear cell RCC were randomly assigned to PAZ or placebo for 1 year. The starting dose (800 mg) following treatment of 403 pts was lowered to 600 mg to improve tolerability and primary endpoint was changed to disease-free survival (DFS) with PAZ 600 (N = 1135). Primary analysis was performed after 350 DFS events in intent-to-treat (ITT) PAZ 600, and DFS follow-up analysis was performed after an additional 12 months. Secondary endpoints included DFS with ITT PAZ 800 and ITT ALL, and safety. Results: Disease characteristics were similar between arms. The primary analysis results of DFS ITT 600 were not significant [HR: 0.862; 95% CI, 0.699, 1.063; p = 0.165] (Table). The secondary endpoint of DFS in ITT PAZ 800 and ITT ALL yielded 31% and 20% risk reduction, respectively. Updated DFS analysis in ITT 600 showed a higher HR with longer follow up. Increased ALT and AST were the most common adverse events leading to treatment discontinuation in the PAZ 600 (ALT 16% and AST 5%) and PAZ 800 (ALT 18% and AST 7%) groups. Conclusions: The study did not meet the primary DFS endpoint in ITT 600; however, a 31% decrease in the risk of recurrence was observed in ITT 800. The safety profiles in the 600 mg and 800 mg groups were similar and consistent with PAZ prior experience. Clinical trial information: NCT01235962. [Table: see text]

Treatment of renal cell carcinoma: Current status and future directions

“…There are currently 7 large, multicenter, placebo‐controlled, phase 3 clinical trials that explore the role of adjuvant systemic treatment in RCC (Table ) . ARISER was the first study to investigate the addition of a targeted agent, girentuximab, a chimeric immunoglobulin G1 (IgG1+) monoclonal antibody to carbonic anhydrase IX, in the adjuvant setting .…”

“…Results were recently presented from a different phase 3 study (PROTECT) investigating pazopanib in patients with locally advanced RCC postnephrectomy . In total, 1538 patients were randomly assigned to receive either pazopanib or placebo for 1 year.…”

What Survival Benefits are Needed to Make Adjuvant Sorafenib Worthwhile After Resection of Intermediate- or High-Risk Renal Cell Carcinoma? Clinical Investigators’ Preferences in the SORCE Trial

“…Toxicity also occurred in PROTECT, leading to a reduction in the starting dose of pazopanib from 800 mg to 600 mg daily [20]. The toxicity reported in these three trials highlights the importance of considering the potential benefits, harms, and each individual patient's preferences when making decisions about adjuvant targeted therapy.…”

“…The ASSURE trial (one year of sunitinib versus one year of sorafenib versus placebo, n = 1943) showed no differences in either its primary endpoint of DFS (for sunitinib versus placebo the HR was 1.02; p = 0.80, for sorafenib versus placebo the HR was 0.97; p = 0.72), or in OS [19]. The PROTECT trial (one year of pazopanib versus placebo, n = 1538) did not show a statistically significant improvement in its primary endpoint of DFS (HR 0.86; p = 0.17) [20].…”

New research in kidney cancer, ASCO 2017

“…At ASCO 2017, researchers presented the results of a randomized, phase 3 study evaluating adjuvant pazopanib compared to placebo in patients with locally advanced RCC after nephrectomy at high risk for recurrence. 8 This study (the PROTECT trial) enrolled a total of 1538 patients with resected pT2 (high-grade), pT3 or greater clear-cell RCC. Subjects were randomized to receive pazopanib or placebo for one year.…”