An 8-week rotating treatment schedule of pazopanib and everolimus did not prolong disease progression, result in fewer toxic effects, or improve quality of life compared with continuous treatment with pazopanib alone among patients with metastatic clear cell renal cell carcinoma (RCC), according to the results of the ROPETAR ( Identifier: NCT01408004) study published in JAMA Oncology.1

The standard of care for patients with advanced disease is first-line treatment with a vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) followed by second-line treatment with a mammalian target of rapamycin (mTOR) inhibitor. Most patients given these drugs will eventually develop resistance leading to progression, though resistance to VEGFR-TKI is reversible for many patients after drug withdrawal.

“Reversible resistance is observed relatively frequently in renal cell carcinoma and has been described in retrospective case studies,” Geert A. Cirkel, MD, of the University Medical Center Utrecht in the Netherlands told Cancer Therapy Advisor. “Several potential mechanisms have been described including dynamic epigenetic modulations and shifts in clonal homeostasis.”

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The researchers hypothesized that a rotating schedule of pazopanib and everolimus might reduce the significant toxic effects associated with discontinuation of these drugs, leading to improved quality of life.

In the ROPETAR study, 101 patients with treatment-naive metastatic clear cell RCC were randomly assigned to an 8-week rotating treatment schedule (52 patients) of pazopanib 800 mg per day and everolimus 10 mg per day or continuous treatment (49 patients) with pazopanib 800 mg per day until disease progression.

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The study failed to meet its primary endpoint. The 1-year progression-free survival for the rotating arm was 45% compared with 32% for the continuous pazopanib arm. The median time to first progression or death for the rotating arm was 7.4 months compared with 9.4 months for the continuous pazopanib arm (P = .37).  Patients assigned to the rotating arm had higher rates of mucositis, anorexia, and dizziness, and had no improvements in quality of life compared with the continuous treatment arm.