Randomized phase III trial of adjuvant pazopanib versus placebo after nephrectomy in patients with localized or locally advanced renal cell carcinoma Journal Article
| Authors: | Motzer, R. J.; Haas, N. B.; Donskov, F.; Gross-Goupil, M.; Varlamov, S.; Kopyltsov, E.; Lee, J. L.; Melichar, B.; Rini, B. I.; Choueiri, T. K.; Zemanova, M.; Wood, L. A.; Reaume, M. N.; Stenzl, A.; Chowdhury, S.; Lim, H. Y.; McDermott, R.; Michael, A.; Bao, W.; Carrasco-Alfonso, M. J.; Aimone, P.; Voi, M.; Doehn, C.; Russo, P.; Sternberg, C. N.; on behalf of the PROTECT investigators |
| Article Title: | Randomized phase III trial of adjuvant pazopanib versus placebo after nephrectomy in patients with localized or locally advanced renal cell carcinoma |
| Abstract: | Purpose: This phase III trial evaluated the efficacy and safety of pazopanib versus placebo in patients with locally advanced renal cell carcinoma (RCC) at high risk for relapse after nephrectomy. Patients and Methods: A total of 1,538 patients with resected pT2 (high grade) or ≥ pT3, including N1, clear cell RCC were randomly assigned to pazopanib or placebo for 1 year; 403 patients received a starting dose of 800 mg or placebo. To address toxicity attrition, the 800-mg starting dose was lowered to 600 mg, and the primary end point analysis was changed to disease-free survival (DFS) for pazopanib 600 mg versus placebo (n = 1,135). Primary analysis was performed after 350 DFS events in the intent-totreat (ITT) pazopanib 600 mg group (ITT600mg), and DFS follow-up analysis was performed 12 months later. Secondary end point analyses included DFS with ITT pazopanib 800 mg (ITT800mg) and safety. Results: The primary analysis results of DFS ITT600mg favored pazopanib but did not show a significant improvement over placebo (hazard ratio [HR], 0.86; 95% CI, 0.70 to 1.06; P =.165). The secondary analysis of DFS in ITT800mg (n = 403) yielded an HR of 0.69 (95% CI, 0.51 to 0.94). Follow-up analysis in ITT600mg yielded an HR of 0.94 (95% CI, 0.77 to 1.14). Increased ALT and AST were common adverse events leading to treatment discontinuation in the pazopanib 600 mg (ALT, 16%; AST, 5%) and 800 mg (ALT, 18%; AST, 7%) groups. Conclusion: The results of the primary DFS analysis of pazopanib 600 mg showed no benefit over placebo in the adjuvant setting. © 2017 by American Society of Clinical Oncology. |
| Keywords: | adult; controlled study; aged; aged, 80 and over; disease-free survival; middle aged; young adult; major clinical study; clinical trial; fatigue; cancer recurrence; angiogenesis inhibitor; placebo; advanced cancer; diarrhea; dose response; drug efficacy; drug safety; drug withdrawal; hypertension; side effect; disease free survival; chemotherapy, adjuvant; follow up; cancer grading; nausea; randomized controlled trial; stomatitis; vomiting; pathology; dose-response relationship, drug; pyrimidines; vascularization; renal cell carcinoma; kidney neoplasms; nephrectomy; abdominal pain; arthralgia; asthenia; backache; rash; alanine aminotransferase; aspartate aminotransferase; kidney tumor; carcinoma, renal cell; sulfonamide; multicenter study; sulfonamides; adjuvant chemotherapy; pazopanib; headache; phase 3 clinical trial; hypothyroidism; pyrimidine derivative; hand foot syndrome; angiogenesis inhibitors; alopecia; placebos; dysgeusia; hair discoloration; dysphoria; upper abdominal pain; neoplasm grading; very elderly; humans; human; male; female; priority journal; article; loss of appetite |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 35 |
| Issue: | 35 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2017-12-10 |
| Start Page: | 3916 |
| End Page: | 3923 |
| Language: | English |
| DOI: | 10.1200/jco.2017.73.5324 |
| PUBMED: | 28902533 |
| PROVIDER: | scopus |
| PMCID: | PMC6018511 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 January 2018 -- Source: Scopus |
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