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The interim study findings demonstrated that RAD001 significantly extendedthe time without tumor growth from 1.9 to 4 months and reduced the risk ofcancer 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 OralRAD001 given Daily), will be presented at the 44th annual meeting of theAmerican Society of Clinical Oncology (ASCO) in Chicago, Illinois, US onSaturday, May 31, 2008.
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Earlier this year, an independent data monitoring committee stopped theRECORD-1 trial after interim results showed that patients receiving RAD001experienced a significantly longer time without their cancer worseningcompared to patients receiving placebo. The trial included patients whosecancer had stopped responding to approved treatments for renal cell carcinoma(RCC), such as Nexavar(R) (sorafenib) or Sutent(R) (sunitinib), or both.
RAD001 is a once-daily oral therapy that may offer a new approach tocancer treatment by continuously inhibiting the mTOR protein, a centralregulator of tumor cell division and blood vessel growth in cancer cells.
"This is the first study to show clinical benefit in patients withadvanced kidney cancer who have experienced treatment failure with the mostcommonly used first-line therapies," said Robert J. Motzer, MD, attendingphysician, Memorial Sloan-Kettering Cancer Center, New York, and principalinvestigator of the RECORD-1 trial. "The results show RAD001 extendedprogression-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 beused to submit a new drug application for RAD001 as a treatment for metastaticrenal cell carcinoma.
"As we will see in presentations at the upcoming meeting, RAD001 has thepotential to benefit patients living with a variety of cancers includingneuroendocrine, breast, gastric, and lung," said David Epstein, CEO andPresident of Novartis Oncology. "We look forward to updates from trials inpancreatic neuroendocrine tumors before year-end."
RECORD-1 results
RECORD-1 is the largest Phase III clinical trial investigating the effectsof an oral mTOR inhibitor in metastatic RCC. It is a randomized, double-blindplacebo-controlled multicenter trial of more than 400 patients with RCC whosecancer worsened despite prior treatment, including Nexavar or Sutent, or both.In addition, prior therapy with Avastin, interferon, and interleukin-2 wasallowed.
The primary endpoint of RECORD-1 was progression-free survival (PFS)assessed via a blinded, independent central review and defined as the amountof time between randomization and first documented disease progression ordeath due to any cause. Results of the study demonstrated a statisticallysignificant 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. 1.9months, respectively).
Secondary endpoints included comparison of overall survival, objectiveresponse rate, quality of life, safety, and pharmacokinetics. There was nosignificant difference in overall survival between the RAD001 and placebogroups (hazard ratio = 0.83 with 95% CI 0.50 to 1.37; p-value = 0.23). Thestudy design allowed patients to be unblinded at the time of radiologicaldisease progression; patients receiving placebo were allowed to cross over toreceive RAD001. There was no significant difference in objective response ratebetween the RAD001 and placebo groups (1% vs. 0% of responders). However, in acentral review among patients evaluable for best percentage change in targetlesions (223 and 107 in RAD001 an
