PROTECT
Adjuvant pazopanib versus placebo after nephrectomy in patients with localized or locally advanced renal cell carcinoma (PROTECT)
Phase 3N = 1,538NCT01235962
- Population
- Resected pT2 (high grade) or pT3 or higher, including N1, clear cell renal cell carcinoma.
- Design
- Randomised, double-blind, placebo-controlled phase 3 trial of pazopanib or placebo for 1 year. 403 patients started at 800 mg; the starting dose was then lowered to 600 mg because of toxicity attrition and the primary analysis was changed to pazopanib 600 mg versus placebo (1,135 patients). Primary analysis after 350 DFS events in the pazopanib 600 mg group; a follow-up DFS analysis followed 12 months later.
- Primary endpoint
- DFS
- Arms
- Pazopanib (experimental, n = 769): Pazopanib 800 mg or (after the dose change) 600 mg daily for 1 year
- Placebo (control, n = 769): Placebo for 1 year
- People
- Motzer RJ
DFSHR 0.86 (95% CI 0.70–1.06)DFSHR 0.69 (95% CI 0.51–0.94)DFSHR 0.94 (95% CI 0.77–1.14)OSHR 1.00 (95% CI 0.80–1.26)
Show the numbers
| Endpoint | Analysis | Pazopanib | Placebo | Effect |
|---|---|---|---|---|
| DFSITT600mg (pazopanib 600 mg starting dose versus placebo, n=1,135) | primaryMotzer 2017 | — | — | HR 0.86 (95% CI 0.70–1.06)P=0.165Favoured pazopanib numerically but not significant. |
| DFSITT800mg (pazopanib 800 mg starting dose versus placebo, n=403) | exploratoryMotzer 2017 | — | — | HR 0.69 (95% CI 0.51–0.94)Secondary endpoint analysis per the abstract (recorded as 'exploratory' because the schema has no 'secondary' value); 403 patients with an 800 mg starting dose. |
| DFSITT600mg (pazopanib 600 mg starting dose versus placebo, n=1,135) | long term-updateMotzer 2017 | — | — | HR 0.94 (95% CI 0.77–1.14)Follow-up analysis 12 months after the primary analysis. |
| OSRandomised patients (pazopanib n=769, placebo n=769) | finalMotzer 2021 | — | — | HR 1.00 (95% CI 0.80–1.26)P> 0.9Nominal p-value. Median follow-up 76 months with pazopanib and 77 months with placebo. |
| Endpoint | Analysis | Pazopanib | Placebo | Effect |
|---|---|---|---|---|
| DFSITT600mg (pazopanib 600 mg starting dose versus placebo, n=1,135) | primaryMotzer 2017 | — | — | HR 0.86 (95% CI 0.70–1.06)P=0.165Favoured pazopanib numerically but not significant. |
| DFSITT800mg (pazopanib 800 mg starting dose versus placebo, n=403) | exploratoryMotzer 2017 | — | — | HR 0.69 (95% CI 0.51–0.94)Secondary endpoint analysis per the abstract (recorded as 'exploratory' because the schema has no 'secondary' value); 403 patients with an 800 mg starting dose. |
| DFSITT600mg (pazopanib 600 mg starting dose versus placebo, n=1,135) | long term-updateMotzer 2017 | — | — | HR 0.94 (95% CI 0.77–1.14)Follow-up analysis 12 months after the primary analysis. |
| OSRandomised patients (pazopanib n=769, placebo n=769) | finalMotzer 2021 | — | — | HR 1.00 (95% CI 0.80–1.26)P> 0.9Nominal p-value. Median follow-up 76 months with pazopanib and 77 months with placebo. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| DFS | 0.86 | 0.7–1.06 |
| DFS | 0.69 | 0.51–0.94 |
| DFS | 0.94 | 0.77–1.14 |
| OS | 1 | 0.8–1.26 |
Appears in
Sources
Motzer RJ, Haas NB, Donskov F, Gross-Goupil M, Varlamov S, Kopyltsov E, et al. Randomized Phase III Trial of Adjuvant Pazopanib Versus Placebo After Nephrectomy in Patients With Localized or Locally Advanced Renal Cell Carcinoma. J Clin Oncol. 2017;35(35):3916-3923.
Motzer RJ, Russo P, Haas N, Doehn C, Donskov F, Gross-Goupil M, et al. 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. Eur Urol. 2021;79(3):334-338.