Everolimus, also called Certican, can stall progression of for patients with renal cell carcinoma who have experienced failure with other treatment regimens, according to an Article released on July 23, 3008 in The Lancet.
Renal cell carcinoma, or metastatic kidney cancer, like other cancers, is believed to be caused by the abnormal functioning of signaling pathways in cells. Both the overproduction of VEGF factor and the von Hippel-Lindau tumour suppressor gene have been associated in particular with renal cancer. Previously, the outlook for a patient with metastatic kidney cancer was bleak. Now, some drugs have been successful to help control the receptor for VEGF, but an alternative is needed for the patients who do not respond.
Everolimus, a derivative of rapomycin, affects an important intracellular signaling pathway regulating proliferation, growth, cellular metabolism, and angiogenesis. To test everolimus’ efficacy, Dr. Robert Motzer, of Memorial Sloan-Kettering Cancer Center, New York, USA, and colleagues performed a randomized, controlled phase III trial in patients whose metastatic kidney cancer had continued to progress despite treatment with sunitinib, sorafenib, or both. These patients were randomly assigned in a 2:1 ratio: 272 patients to receive 10 mg of everolimus once daily, or 138 patients with a placeblo. This treatment, in tandem with high quality supportive care, was examined in terms of progression-free survival, with the study ending after 290 progression events occurred.
It was found that there was a significant difference in efficacy, which favored the group that was administered everolimus. The ethical implications of this progression, as it did not allow the placebo patients access to the drug, led to the trial’s termination after 191 progression events. Progression events were observed in 37% (101 of 272) of patients in the everolimus group and 65% (90 of 138) of the placebo group.
Further analysis indicated that patients administered everolimus were less than one third as likely to experience disease progression. The median length of progression free survival time was 4 months in the medicated group, approximately twice that of the placebo.
There were some adverse events, including stomatitis, rash, and fatigue, which were more common in the everolimus group, but were mostly mild or moderate in severity. Pneumotitis was also observed in 22 patients on everolimus, of whom eight had a severity grade 3.
In concludion, the authors have high hopes for everolimus. “On the basis of the results of this trial, we believe that everolimus should now be considered as the standard-of-care in patients with metastatic renal cell carcinoma whose disease has progressed after treatment with VEGF-targeted therapies.” They say.
Dr Jennifer J Knox, Princess Margaret Hospital, University of Toronto, ON, Canada, contributed an accompanying Comment, which encourages consideration of this new medication: “I would encourage international regulatory boards to accept these data as evidence of clinical benefit of everolimus in metastatic renal cell carcinoma that has progressed on prior targeted therapies.”
Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial
Robert J Motzer, Bernard Escudier, Stéphane Oudard, Thomas E Hutson, Camillo Porta, Sergio Bracarda, Viktor Grünwald, John A Thompson, Robert A Figlin, Norbert Hollaender, Gladys Urbanowitz, William J Berg, Andrea Kay, David Lebwohl, Alain Ravaud, for the RECORD-1 Study Group
Published The Lancet Online July 23, 2008
DOI:10.1016/S0140-6736(08)61039-9
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Progression-free survival as endpoint in metastatic RCC?
Jennifer J Knox
Published The Lancet Online July 23, 2008
DOI:10.1016/S0140-6736(08)61040-5
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Written by Anna Sophia McKenney