The FINANCIAL — New data show RAD001 (everolimus) may provide an important new treatment option for patients with advanced kidney cancer who have failed standard therapies.
According to Novartis, the interim study findings demonstrated that RAD001 significantly extended the time without tumor growth from 1.9 to 4 months and reduced the risk of cancer progression by 70% (hazard ratio = 0.30 with 95% CI 0.22 to 0.40; p-value < 0.0001). The study, RECORD-1 (REnal Cell cancer treatment with Oral RAD001 given Daily), will be presented at the 44th annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, Illinois, US on Saturday, May 31, 2008.
Earlier this year, an independent data monitoring committee stopped the RECORD-1 trial after interim results showed that patients receiving RAD001 experienced a significantly longer time without their cancer worsening compared to patients receiving placebo. The trial included patients whose cancer had stopped responding to approved treatments for renal cell carcinoma (RCC), such as Nexavar (sorafenib) or Sutent (sunitinib), or both.
RAD001 is a once-daily oral therapy that may offer a new approach to cancer treatment by continuously inhibiting the mTOR protein, a central regulator of tumor cell division and blood vessel growth in cancer cells.
"This is the first study to show clinical benefit in patients with advanced kidney cancer who have experienced treatment failure with the most commonly used first-line therapies," said Robert J. Motzer, MD, attending physician, Memorial Sloan-Kettering Cancer Center, New York, and principal investigator of the RECORD-1 trial. "The results show RAD001 extended progression-free survival in patients regardless of their prior treatments, risk status, age, or gender."
During the second half of 2008, the interim results from RECORD-1 will be used to submit a new drug application for RAD001 as a treatment for metastatic renal cell carcinoma.
"As we will see in presentations at the upcoming meeting, RAD001 has the potential to benefit patients living with a variety of cancers including neuroendocrine, breast, gastric, and lung," said David Epstein, CEO and President of Novartis Oncology. "We look forward to updates from trials in pancreatic neuroendocrine tumors before year-end."
RECORD-1 results
RECORD-1 is the largest Phase III clinical trial investigating the effects of an oral mTOR inhibitor in metastatic RCC. It is a randomized, double-blind placebo-controlled multicenter trial of more than 400 patients with RCC whose cancer worsened despite prior treatment, including Nexavar or Sutent, or both. In addition, prior therapy with Avastin, interferon, and interleukin-2 was allowed.
The primary endpoint of RECORD-1 was progression-free survival (PFS) assessed via a blinded, independent central review and defined as the amount of time between randomization and first documented disease progression or death due to any cause. Results of the study demonstrated a statistically significant improvement in PFS for RAD001 compared to placebo (hazard ratio = 0.30 with 95% CI 0.22 to 0.40; p-value < 0.0001; median PFS 4 months vs. 1.9 months, respectively).
Secondary endpoints included comparison of overall survival, objective response rate, quality of life, safety, and pharmacokinetics. There was no significant difference in overall survival between the RAD001 and placebo groups (hazard ratio = 0.83 with 95% CI 0.50 to 1.37; p-value = 0.23). The study design allowed patients to be unblinded at the time of radiological disease progression; patients receiving placebo were allowed to cross over to receive RAD001. There was no significant difference in objective response rate between the RAD001 and placebo groups (1% vs. 0% of responders). However, in a central review among patients evaluable for best percentage change in target lesions (223 and 107 in RAD001 and placebo arms, respectively), tumor shrinkage was observed in 50% of patients receiving RAD001 during the double-blind portion of the study versus 8% of patients receiving placebo. Quality of life measurements taken throughout the study showed no significant difference between the RAD001 and placebo groups.
Safety findings in the study were consistent with those seen in prior Phase II studies. The most frequent adverse events in patients who took RAD001 included mouth sores (40%), feelings of weakness (37%), and rash (25%). There was a low incidence of grade 3 or 4 drug-related adverse events (> 1% of patients listed): mouth sores (3%), lung inflammation (3%), infection (3%), tiredness/feelings of weakness (4%), diarrhea (1%), mucosal inflammation (1%), and difficulty breathing (1%). The trial had a low rate of adverse drug reactions leading to discontinuation among patients who took RAD001 (6%).
Discussion about this post