Oral medication prolongs progression-free survival in patients who have failed conventional treatment.

STOCKHOLM—Patients with advanced renal cell carcinoma (RCC) who are treated with RAD001 after failing standard therapy have more than twice the progression-free survival (PFS) as placebo-treated patients, new data show.  

RAD001 is an investigational once-daily oral inhibitor of mammalian target of rapamycin (mTOR), a key protein kinase regulating cell proliferation and angiogenesis.

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“Importantly, our findings demonstrate for the first time that a drug can confer significant benefit after approved therapies have failed, thereby satisfying an unmet medical need,” said Bernard Escudier, MD, head of the Immunotherapy and Innovative Therapy Unit, Institut Gustave Roussy, Villejuif, France. He reported findings here at the 33rd Annual Congress of the European Society of Medical Oncology.

The data come from the Renal Cell Cancer Treatment with Oral RAD001 (RECORD-1) study, the largest phase 3 trial to date to assess the effects of an oral mTOR inhibitor in metastatic RCC patients whose cancer worsened despite conventional treatment with the multitargeted receptor tyrosine kinase inhibitors (TKIs) sorafenib and sunitinib, used individually or together.

Patients were randomized in a 2:1 design to receive RAD001 10 mg/day or placebo plus best supportive care in both groups. Prior therapy with bevacizumab or[? Or did patients have to use both?] interferon was allowed. Participants were stratified according to Memorial Sloan-Kettering Cancer Center risk criteria and prior anticancer therapy. PFS, which was assessed by blinded central independent review, was the trial’s primary end point.

The analysis showed a median PFS of five months in patients randomized to RAD001 vs. 1.9 months in the placebo cohort, for a risk reduction of 67%. In addition, 25% of RAD001-treated patients remained progression-free beyond 10 months of treatment.

The PFS benefit observed with RAD001 occurred regardless of patients’ prior treatments, risk status, age, or gender. Those who had prior treatment with sorafenib tended to benefit more than patients who had been treated with sunitinib.

Overall, 10% of patients taking RAD001 experienced adverse effects that led to discontinuation  vs. 1% of those taking placebo. Four percent of patients in the active-treatment group required dose reductions compared with less than 1% in the placebo group. Grade 3-4 side effects were very infrequent and most often included mouth sores, rash, weakness, and fatigue of all grades. Quality of life was similar in the two groups.

Earlier this year, the trial was stopped after interim results showed that RAD001-treated patients had significantly longer PFS survival than placebo-treated patients.

Dr. Escudier said that future studies will explore whether RAD001 is effective as first-line therapy in advanced RCC and whether combination therapy with TKIs may provide further benefit.

He added that he expects that the drug, if approved, will benefit most patients with advanced kidney disease. “It’s safe and easy to use,” he said, “and there is a need for such an agent given that virtually all patients will eventually fail TKI therapy.”

The FDA recently granted priority review for RAD001 as a treatment for advanced RCC.