BOULDER, ColoradoIn a multi-national phase III trial, Vidaza (azacitidine) improved overall survival by 74% in patients with higher-risk myelodysplastic syndromes, compared with conventional care regimens. Median survival with Vidaza was 24.4 months vs 15 months for conventional care (HR 0.58, P = .0001), Pharmion Corporation said in announcing the results. Two-year survival rates were 50.8% vs 26.2% (P < .0001).
The trial randomized 358 higher-risk MDS patients on a 1:1 ratio to receive either Vidaza, 75 mg/m2/d SC for 7 days every 28 days, or conventional care consisting of one of three physician-selected regimens: best supportive care (BSC) alone, low-dose cytarabine plus BSC, or standard chemotherapy plus BSC. Pharmion said that full study results will be presented at an upcoming medical meeting.
Vidaza was FDA approved in May 2004 for the subcutaneous treatment of all five MDS subtypes, based on trial data showing a reduced need for transfusions with Vidaza, and in 2007 it received approval for IV administration. The company will also file a supplemental NDA to include these data in the US prescribing information.
Vidaza is the first in the new class of drugs known as demethylation agents. It is also classified as an epigenetic therapy, since DNA methylation is an epigenetic regulator of gene expression.
Epigenetic changes can silence gene expression and, unlike DNA mutations, may be reversed by targeting the mechanisms involved. The epigenetic approach to cancer therapy, thus, is to reactivate the silenced genes through targeted epigenetic therapy, re-establishing the cancer cell's natural mechanisms to control abnormal growth.
'Very exciting results'
"With these very exciting results for Vidaza, survival should now be the standard by which we evaluate treatment options for higher-risk MDS," said Alan F. List, MD, chief of the Malignant Hematology Division and Deputy Physician in Chief at the H. Lee Moffitt Cancer Center & Research Institute, Tampa. "Importantly, as the first and only epigenetic therapy to have demonstrated a survival benefit in any cancer, these findings should accelerate exploration of Vidaza in other malignancies where hypermethylation is believed to play a key role in tumor development and progression."