Updated study findings from the RECORD-1 ( REnal Cell cancer treatment with Oral RAD001 given Daily ) study have shown that patients with advanced kidney cancer receiving RAD001 had no tumour growth for nearly 5 months versus 1.9 months for patients receiving placebo ( hazard ratio = 0.33; p< 0.001 ). In addition, after more than 10 months of treatment with RAD001, 25% of patients still had no tumour growth.
RAD001, an oral once-daily inhibitor of mTOR, is an investigational drug being studied in multiple tumour types. In cancer cells, RAD001 provides continuous inhibition of mTOR, a protein that acts as a central regulator of tumour cell division, cell metabolism and blood vessel growth.
The active ingredient in RAD001 is Everolimus.
EECORD-1 is a Phase III clinical trial investigating the effects of an oral mTOR inhibitor in metastatic renal cell carcinoma ( RCC ). It is a randomised, double-blind, placebo-controlled multicentre trial of more than 400 patients with RCC whose cancer worsened despite prior treatment including Nexavar ( Sorafenib ) or Sutent ( Sunitinib ), or both. In addition, prior therapy with Avastin ( Bevacizumab ), 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 randomisation 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 ( HR= 0.33; p< 0.001; median PFS 4.9 months vs. 1.9 months, respectively ).
Secondary endpoints included comparison of overall survival, objective response rate, quality of life and safety. There was no significant difference in overall survival between the RAD001 and placebo groups ( HR= 0.82; p= 0.137 ).
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 ( 2% 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 ), tumour shrinkage was observed in 50% of patients receiving RAD001 during the double-blind portion of the study vers 8% of patients receiving placebo.
Quality of life measurements taken throughout the study showed no significant difference between the RAD001 and placebo groups.
The most frequent adverse events in patients who took RAD001 included mouth sores ( 36% ), rash ( 28% ), feelings of weakness ( 23% ) and tiredness ( 22% ). There was a low incidence of grade 3 or 4 drug-related adverse events ( > 1% ): infection ( 4% ), mouth sores ( 3% ), tiredness ( 3% ), feelings of weakness ( 2% ), lung inflammation ( 2% ), diarrhea ( 2% ), mucosal inflammation ( 1% ), vomiting ( 1% ) and difficulty breathing ( 2% ). The trial had a low rate of adverse drug reactions leading to discontinuation among patients who took RAD001 ( 7% ).
Renal cell cancer accounts for 2% of all new cancer cases worldwide with occurrence rates rising steadily around the world. In the UK, RCC has increased by 22% over the last ten years. Each year, approximately 6,600 people in the UK are diagnosed with kidney cancer, which also causes around 3,600 deaths each year. There are several types of RCC, but the most common, called clear cell, accounts for 80% of diagnoses. In RCC, cancer cells develop in the lining of the kidney's tubes and grow into a tumour.
Source: 33rd European Society for Medical Oncology ( ESMO ) Congress, 2008
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