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FDA advisory committee to consider adjuvant sunitinib for RCC
Phase 3 results for sunitinib as adjuvant treatment for high risk RCC have been mixed.
Adjuvant pazopanib provided no disease-free survival benefit compared with placebo in the randomized phase 3 PROTECT trial of patients with locally advanced renal cell carcinoma at high risk for relapse after nephrectomy.
In the primary analysis for disease-free survival among 571 patients treated for 1 year with 600 mg of pazopanib and 564 who received placebo, no significant improvement was seen with pazopanib (hazard ratio, 0.86). In a follow-up analysis 12 months later, the hazard ratio was 0.94. Secondary analysis in 403 additional patients who were treated with 800 mg of pazopanib before the dose was lowered to 600 mg due to intolerance and toxicity attrition showed a benefit with pazopanib (HR, 0.69), but this group represented only a third of the study population, reported Robert J. Motzer, MD, of Memorial Sloan Kettering Cancer Center, New York, and his colleagues. The study results were published online in the Journal of Clinical Oncology.
Dr. Robert J. Motzer
Common adverse events leading to treatment discontinuation included increased alanine transaminase and aspartate transaminase levels, which occurred in 16% and 5% of patients treated with 600 mg, respectively, and in 18% and 7% of patients treated with 800 mg, respectively. Four grade 5 adverse events occurred in the pazopanib groups (vs. 2 in the placebo group), and one of the deaths (in a patient who received 800 mg dosing) involved cardiomyopathy that was considered to be related to treatment, the investigators said (J Clin Oncol. 2017 Sep 13. doi: 10.1200/JCO.2017.73.5324).
The study comprised adults with resected pT2 or pT3 and greater disease, including N1, clear cell renal cell carcinoma, who were enrolled between Dec. 9, 2010, and Sept. 10, 2013, from 263 centers in 26 countries. Primary analysis was done after 350 disease-free events occurred in the intent-to-treat population receiving 600 mg.
The difference in treatment effect between those receiving 600 mg and 800 mg of pazopanib could be explained by the different starting dose, or by better performance of the placebo arm in the 600 mg group, the investigators noted.
As for overall survival, the results are inconclusive, because the data are not mature, they said.
Novartis supported the study. Dr. Mercer reported consulting or advisory roles with Pfizer, Novartis, Eisai, and Exelixis, and research funding to his institution from Pfizer, GlaxoSmithKline, Bristol-Myers Squibb, Eisai, Novartis, and Genentech. Numerous coauthors also reported financial relationships with pharmaceutical companies.