As reported in the Journal of Clinical Oncology by Motzer et al, the phase III PROTECT trial showed no significant disease-free survival benefit for adjuvant pazopanib at 600 mg vs placebo after nephrectomy in patients with localized or locally advanced renal cell carcinoma at high risk of relapse.
In the trial, 1,538 patients with resected pT2 (high grade) or ≥ pT3, including N1, clear cell disease were randomized to receive pazopanib (n = 769) or placebo (n = 769) once daily for 1 year. Of them, 403 patients received the initial starting dose of 800 mg of pazopanib (n = 198) or placebo (n = 205). Due to higher than expected attrition from toxicity, the starting dose was lowered to 600 mg, and the primary endpoint analysis was changed to disease-free survival for pazopanib at 600 mg (n = 571) vs placebo (n = 564). The primary analysis was conducted after 350 disease-free survival events in the intent-to-treat (ITT) pazopanib 600-mg group (ITT600mg); a disease-free survival follow-up analysis was performed 12 months later.
Disease-Free Survival Analyses
The median duration of follow-up for the primary analysis was 30 to 31 months; the hazard ratio (HR) for disease-free survival in the ITT600mg population favored pazopanib but was not statistically significant (HR = 0.86, P = .165). The analysis in the ITT800mg population after median follow-up of 47 months showed a significant benefit of pazopanib (HR = 0.69, 95% confidence interval = 0.51–0.94). Follow-up analysis in the ITT600mg population showed a hazard ratio of 0.94 (95% CI = 0.77–1.14). Follow-up analysis in the ITT800mg population showed a hazard ratio of 0.66 (95% CI = 0.49–0.90).
The most common grade 3 or 4 adverse events with pazopanib at 600 mg were hypertension (25%), increased alanine aminotransferase (ALT; 16%), and increased aspartate aminotransferase (AST; 6%). Increased levels of ALT and AST led to treatment discontinuation in 16% and 5% of the pazopanib 600-mg group and 18% and 7% of the pazopanib 800-mg group, respectively.
The investigators concluded: “Findings from PROTECT demonstrated differences in outcome between the 600- and 800-mg starting dose groups; however, the study did not meet its primary [disease-free survival] endpoint. The results of the primary analysis of [disease-free survival] with pazopanib 600 mg showed no benefit over placebo in the adjuvant setting. The safety profile of pazopanib was consistent with prior experience.”
The study was supported by Novartis and, previously, by GlaxoSmithKline.
Robert J. Motzer, MD, of Memorial Sloan Kettering Cancer Center, is the corresponding author of the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.