Results from a Randomized Phase III Trial of Decitabine versus Supportive Care or Low-Dose Cytarabine for the Treatment of Older Patients with Newly Diagnosed.

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Results from a Randomized Phase III Trial of Decitabine versus Supportive Care or Low-Dose Cytarabine for the Treatment of Older Patients with Newly Diagnosed AML Thomas XG et al. Proc ASCO 2011;Abstract 6504.

Thomas XG et al. Proc ASCO 2011;Abstract Accrual: 485 (Closed) Treatment choice: Supportive care or Ara-C, 20 mg/m 2 SC qd x 10 every 4 wks Objectives: Overall survival (primary) Remission rates (CR + CRp) and safety (secondary) Eligibility ≥65 years old Newly diagnosed de novo or secondary AML Poor- or intermediate-risk cytogenetics (SWOG criteria) No prior treatment ECOG PS: 0-2 R Decitabine, 20 mg/m 2 IV qd x 5 every 4 wks Decitabine vs Supportive Care or Cytarabine (Ara-C) for AML in Older Patients

With permission from Thomas XG et al. Proc ASCO 2011;Abstract Overall Survival (396 Deaths, 2009 Clinical Cutoff) Time (mo) Patients Alive (%) N Death (%)Median, mo95% CI (81)7.7(6.2, 9.2) (82)5.0(4.3, 6.3) HR (95% CI): 0.85 (0.69, 1.04) Log-rank p-value: Decitabine Total TC

With permission from Thomas XG et al. Proc ASCO 2011;Abstract Overall Survival (446 Deaths, 2010* Clinical Cutoff) Time (mo) Patients Alive (%) N Death (%)Median, mo95% CI (90)7.7(6.2, 9.2) (93)5.0(4.3, 6.3) HR (95% CI): 0.82 (0.68, 0.99) Log-rank p-value: (nominal) Decitabine Total TC * Ad hoc

Remission Rates at 2009 Clinical Cutoff* Treatment CR + CRp (n, %) CRi (n, %) Decitabine (n = 242)43 (17.8) † 24 (9.9) Treatment choice, TC (n = 243)19 (7.8) † 7 (2.9) TC, cytarabine (n = 215)18 (8.4)6 (2.8) TC, supportive care (n = 28)1 (3.6) * Assessed by expert panel, based on IWG 2003 † p-value = 0.001; odds ratio 2.5 CRp = complete remission with incomplete platelet recovery CRi = complete remission with incomplete blood count recovery Thomas XG et al. Proc ASCO 2011;Abstract 6504.

Grade 3/4 Infections and Myelosuppression* Adverse event (%) Supportive care (n = 29) Cytarabine (n = 208) Decitabine (n = 238) Febrile neutropenia02532 Pneumonia/bronchopneumonia14/1019/421/4 Urinary tract infection326 Sepsis/septic shock3/04/26/5 Thrombocytopenia Anemia Neutropenia32032 * On study, in ≥5% of patients in any treatment group Thomas XG et al. Proc ASCO 2011;Abstract 6504.

Author Conclusions In this largest controlled trial for older patients with AML, decitabine versus treatment choice demonstrated: –Trend for improved OS with decitabine at protocol- defined clinical cutoff with 396 deaths; 7.7 months versus 5.0 months with treatment choice, HR = 0.85, p = –Ad hoc mature analysis at clinical cutoff 2010 (446 deaths), OS with decitabine 7.7 months versus 5.0 months with treatment choice, HR = 0.82, nominal p = Similar safety profile with decitabine versus low-dose cytarabine

Investigator Commentary: Results from a Phase III Study of Decitabine versus Supportive Care or Low-Dose Cytarabine for Older Patients with Newly Diagnosed AML As a registration trial, this study showed that although the median survivals were not significantly different, a better outcome was observed with decitabine. With longer follow-up and more data, a more accurate assessment could be made, and after more death events, the data became statistically significant. However, from a clinical perspective, the median difference in overall survival was only 2 months, so I believe the best information emerging from this trial is that administering decitabine to older patients with AML is reasonable, particularly if these patients are not candidates for more intensive regimens. Susan M O’Brien, MD