Date: 2014-12-08
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition, being held December 6-9 in San Francisco, CA
Company: Celgene (USA - NJ)
Product: Vidaza®
Action
mechanism: Vidaza® is a pyrimidine nucleoside analog of cytidine. Vidaza® is believed to exert itsantineoplastic effects by causing hypomethylation of DNA and direct cytotoxicity on abnormal hematopoietic cells in the bone marrow. The concentration of azacitidine required for maximum inhibition of DNA methylation in vitro does not cause major suppression of DNA synthesis. Hypomethylation may restore normal function to genes that are critical for differentiation and proliferation. The cytotoxic effects of azacitidine cause the death of rapidly dividing cells, including cancer cells that are no longer responsive to normal growth control mechanisms. Non-proliferating cells are relatively insensitive to azacitidine.
Disease: acute myeloid leukemia
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On December 8, 2014, Celgene announced that data from two sub-group analyses from AML-001, its phase III study of Vidaza® (azacitidine for injection) compared with conventional care regimens (CCR) in elderly subjects with newly diagnosed acute myeloid leukemia (AML, > 30% blasts), were presented at the 56th American Society of Hematology annual meeting. In this global, multi-center, randomized, open-label pivotal study, patients at least 65 years old with newly diagnosed or secondary AML with > 30% bone marrow blasts were pre-selected to receive one of three regimens per investigator\'s choice: intensive chemotherapy (IC; standard 7+3 regimen), low-dose Ara-C (LDAC; 20 mg SC twice per day for 10 days of each 28-day cycle) or best supportive care (BSC) only. Patients were then randomized to receive either azacitidine (n=241) (75 mg/m2/d SC for 7 days of each 28-day cycle) or their predetermined CCR (n=247). The sub-analyses were not powered to detect statistically significant differences. In the first sub-analysis, Prof. Hervé Dombret reported results from the study focused on patients with AML with morphologic dysplastic changes (AML-MDC).
Of 488 patients in the AML-001 study, 158 (32.4%) had AML-MDC. In these patients, the median overall survival (OS) was twice as long in patients who received azacitidine compared with those who received CCR (12.7 months [95% CI, 7.2, 14.1] vs. 6.3 months [95% CI, 4.3, 9.6] [HR 0.69, 0.48, 0.98, p=0.0357]). The one-year survival rate for patients receiving azacitidine was also higher compared with CCR (50.7% vs. 33.8%; 95% CI, 1.5, 32.2). Rates of patients achieving a complete remission plus morphological complete response with incomplete blood count were 26.7% with azacitidine compared with 19.3% with CCR.
For patients with AML-MDC who were pre-selected to receive LDAC before randomization to azacitidine or CCR (azacitidine n=49, LDAC n=50), median OS was 13.2 months with azacitidine vs. 6.3 months in the LDAC group (HR=0.76, 95% CI, 0.49, 1.19; p=0.23). The one-year survival rate with azacitidine was 55% vs. 31% with LDAC (95% CI, 5.0, 43.0).
Grade 3-4 adverse event rates included: anemia (azacitidine 12%; IC 15%; LDAC 16%; BSC 6%), neutropenia (azacitidine 30%; IC 46%, LDAC 29%; BSC 11%), febrile neutropenia (azacitidine 30%; IC 39%; LDAC 35%; BSC 44%) and thrombocytopenia (azacitidine 28%; IC 31%; LDAC 27%; BSC 11%). \"The sub-analyses into areas of significant medical need in this study, particularly for patients with poor prognostic factors, provide insight into the safety and efficacy of azacitidine in AML-MDC,\" said Professor Dombret . In the second sub-analysis, patients were stratified by cytogenetic risk into either poor-risk (n=170) or intermediate-risk (n=315), which includes cytogenetic normal (CN) patients (n=218).
Median OS (95% CI) in poor-risk patients was significantly prolonged with azacitidine vs. CCR (6.4 months [4.2, 8.1] vs. 3.2 months [2.2, 4.7], respectively; HR=0.68 [0.50, 0.94], p=0.019). In intermediate-risk patients, median OS was 13.0 months (11.2, 16.3) with azacitidine vs. 10.1 months (7.1, 13.3) with CCR (HR=0.90 [0.70, 1.16], p=0.41). The median OS in the CN subgroup was 14.1 months (12.6, 19.5) vs. 10.0 months (6.4, 13.3), respectively (HR=0.81 [0.59, 1.10], p=0.18).
Estimated one-year survival was higher with azacitidine compared with CCR in all cytogenetic risk subgroups. Twice the proportion of azacitidine-treated patients in the poor-risk subgroup were alive at one year compared with CCR patients (30.9% vs 14.0%, respectively; 95% CI, 4.4, 29.5). In the CN subgroup, 60.7% vs. 44.1% of patients were alive at one year in the azacitidine and CCR groups, respectively. The effect on one-year survival in the INT-risk subgroup was also favorable (55.2% for azacitidine vs. 45.5% with CCR).
Grade 3-4 events included: anemia (azacitidine 16%; BSC 5%, LDAC 23%, IC 14%), neutropenia (azacitidine 26%; BSC 5%, LDAC 25%, IC 33%), febrile neutropenia (azacitidine 28%; BSC 28%, LDAC 30%, IC 31%), and thrombocytopenia (azacitidine 24%; BSC 5%, LDAC 28%, IC 21%).
