Long-term Effects of Midostaurin Maintenance Are Unknown in FLT3-mutated AML
At the end of maintenance, 57% and 64% of patients remained in the midostaurin arm or the placebo arm, respectively. There were 16 relapse events after maintenance in the midostaurin arm and 7 relapse
|The following article features coverage from the American Society of Hematology (ASH) 2017 meeting. Click here to read more of Cancer Therapy Advisor's conference coverage.|
Maintenance therapy with midostaurin is well-tolerated among patients with newly diagnosed acute myeloid leukemia (AML), but efficacy outcomes have yet to be confirmed, according to an oral presentation at the 2017 American Society of Hematology (ASH) Annual Meeting in Atlanta, Georgia.1
For the CALGB 10603 (RATIFY) phase 3 study (ClinicalTrials.gov Identifier: NCT00651261), researchers randomly assigned 717 previously untreated patients to undergo induction therapy with daunorubicin and cytarabine plus midostaurin or placebo. Patients with complete remission (CR) received 4 additional cycles of high-dose cytarabine plus midostaurin or placebo, followed by 12 4-week cycles of maintenance therapy with midostaurin or placebo.
Adding midostaurin to induction and consolidation chemotherapy followed by 1 year of maintenance significantly improved overall survival (OS) compared with standard chemotherapy among patients with FLT3-mutant AML.
For this subset analysis, researchers assessed disease-free survival (DFS) to determine the impact of midostaurin vs placebo among patients who underwent maintenance therapy.
The median follow-up was 59 months from enrollment. This post-hoc analysis of the CALGB study showed that 403 patients had CR within 60 days. There were no significant differences in CR rates between patients who received midostaurin or placebo during induction therapy (P = .15). One hundred and seventy-four patients began maintenance therapy while in first complete response (CR1).
At the end of the maintenance, 57% and 64% of patients remained in the midostaurin arm or the placebo arm, respectively. There were 16 relapse events after maintenance in the midostaurin arm, and 7 relapses and 2 deaths in the placebo arm.
Landmark analysis from the end of maintenance revealed no difference in DFS between the 2 arms (hazard ratio, 1.4; 95% CI, 0.63-3.3; P = .38). DFS at 1-year from end of maintenance was 75% [95% CI, 62-84%] in the midostaurin arm compared with 91% [95% CI, 77-96%] in the placebo arm.
No significant difference in OS was observed between the arms from the start of maintenance therapy (hazard ratio for midostaurin, 0.96; 95% CI, 0.58-1.59; P = .86).
The presenter of the study concluded that “midostaurin was well-tolerated, but the definitive impact of maintenance strategies with midostaurin will need to be addressed by randomization.”
Read more of Cancer Therapy Advisor's coverage of the American Society of Hematology (ASH) 2017 meeting by visiting the conference page.
- Larson RA, Mandrekar SJ, Sanford BL, et al. An analysis of maintenance therapy and post-midostaurin outcomes in the international prospective randomized, placebo-controlled, double-blind trial (CALGB 10603/RATIFY [Alliance]) for newly diagnosed acute myeloid leukemia (AML) patients with FLT3 mutations. Oral presentation at: American Society of Hematology 59th Annual Meeting & Exposition; December 9-12, 2017; Atlanta, GA.