Patients enrolled in PROTECT (n=1,538) had either resected pT2 (high grade) or ≥pT3 clear cell RCC after nephrectomy and were randomized to pazopanib vs placebo for 1 year. The starting dose (800 mg) following treatment of 403 patients was lowered to 600 mg to improve tolerability. Subsequently, the primary endpoint was changed to DFS with pazopanib 600 mg (n=1,135), which was performed after 350 DFS events in an intention-to-treat (ITT) analysis. A second DFS analysis was performed after an additional 12 months, and secondary endpoints included (i) DFS with ITT for patients receiving pazopanib 800 mg, (ii) ITT for all patients, and (iii) safety outcomes. Disease characteristics were similar between arms and the results of the primary analysis (DFS ITT for patients receiving pazopanib 600 mg) was not significant (HR 0.86, 95%CI 0.70-1.06). ITT DFS for patients receiving 800 mg (HR 0.69, 95%CI 0.51-0.94) and all patients (HR 0.80, 95%CI 0.68-0.95) was significant, leading to a 31% and 20% risk reduction, respectively. On updated analysis, the 600 mg dose was still insignificant, however the 800 mg dose showed continued risk reduction (HR 0.66, 95%CI 0.49-0.90). There was no difference in OS among any of three analysis groups, however given the prematurity for this endpoint, the final OS analysis will be performed in April 2019. Increased ALT and AST were the most common adverse events leading to treatment discontinuation in the pazopanib 600 mg (ALT 16% and AST 5%) and 800 mg (ALT 18% and AST 7%) cohort.
In conclusion, this study demonstrated a 31% recurrence reduction for patients treated with 800 mg pazopanib in ITT analysis, but this was a secondary objective of the study. The study did not meet the primary DFS endpoint for 600 mg pazopanib and is not recommended for adjuvant therapy following resection of locally advanced RCC.
Clinical trial: NCT01235962
Presented By: Robert J. Motzer, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Co-Authors: Naomi B. Haas, Frede Donskov, Marine Gross-Goupil, Sergei Varlamov, Evgeny Kopyltsov, Jae-Lyun Lee, Bohuslav Melichar, Brian I. Rini, Toni K. Choueiri, Milada Zemanova, Lori A Wood, Dirk Fahlenkamp, Martin Neil Reaume, Arnulf Stenzl, Weichao Bao, Paola Aimone, Christian Doehn, Paul Russo, Cora N. Sternberg
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre
at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 – Chicago, Illinois, USA
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