Abstract
The prognosis for patients with refractory anemia with excess blasts (RAEB) or RAEB in transformation (RAEB-T) ≥ 65 years of age has been poor. These high-risk patients are often not eligible for intensive induction/transplantation regimens or combination chemotherapies, leaving few treatment options besides supportive or palliative care. In the publication of the CALGB trial by Silverman et al (
JCO 2002;20:2429
), no age- and/or risk- related subgroup analyses for azacitidine (Vidaza®) were presented. To assess the treatment effect of azacitidine versus supportive care on survival and time to AML transformation in a homogeneous sample of high-risk patients with MDS, we performed a subgroup analysis on the 191 patients included in the CALGB trial. All patients with a baseline diagnosis of RAEB or RAEB-T who were ≥ 65 years of age were included in the comparative analysis, using intent-to-treat (ITT) principles based on randomization to azacitidine or supportive care. Efficacy was analyzed using three survival endpoints: overall survival, time to death or AML transformation, and time to AML transformation. In all, 31 azacitidine patients and 37 supportive care patients met the criteria for this high-risk subgroup analysis. No significant differences in demographics or disease characteristics between the two groups were observed. For all three survival analyses, a statistically significant difference was observed for patients in the azacitidine group compared with those in the supportive care group. (Table) Median time to transformation to AML, in particular, was prolonged for 24 months in azacitidine patients compared with patients in the supportive care group. A sensitivity analysis of the overall survival results was conducted by performing 10 additional subgroup analyses based on ages ≥ 60 through ≥ 70 years in increments of one year with all overall survival results remaining significant (p < 0.05, except for 2 subgroup analyses based on ages ≥ 60 and ≥ 66 where both p-values were 0.051). The sensitivity results demonstrated robust patient benefit in the subgroup ≥ 65 years of age. The most common adverse event observed with azacitidine was myelosuppression, which decreased in frequency as therapy continued. Azacitidine provided clear treatment effect and patient benefit to this difficult-to-treat, high-risk group of RAEB and RAEB-T patients ≥ 65 years of age by significantly prolonging overall survival and time to AML transformation.Time of Even Analysis
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