Sorafenib, a multikinase inhibitor, appears to improve survival in patients with newly diagnosed FLT3-internal tandem duplication (ITD) mutation-positive acute myeloid leukemia (AML), according to a study published in Cancer.
The addition of sorafenib to treatment in a previous study, the SORAML trial (ClinicalTrials.gov Identifier: NCT00893373), appeared to give patients no overall survival benefit; however, the heterogeneous AML population of that study may have affected the results. Therefore, the current study assessed whether the addition of sorafenib to intensive induction chemotherapy would improve outcomes in patients with FLT3-ITD-mutated AML.
The retrospective study included 183 patients who were newly diagnosed with FLT3-ITD-mutated AML and enrolled in frontline clinical trials of intensive chemotherapy from February 2001 to December 2017. Of these patients, 79 (43%) received intensive chemotherapy plus sorafenib (400 mg twice daily on days 1 through 7 or days 1 through 14 during induction therapy and 400 mg twice daily during consolidation therapy after remission) and 104 (57%) received intensive chemotherapy alone. Lastly, patients from each cohort were matched using propensity score matching; 42 patients were identified in each cohort.
In the matched cohort, the overall response rate was 98% and 83% in the sorafenib cohort and the intensive chemotherapy cohort, respectively (P =.057). Median follow-up duration was 54 months. Median event-free survival was 35 months (95% CI, 1.2-67.9) and 8 months (95% CI, 5.0-11.1) in the sorafenib cohort and in the intensive chemotherapy cohort, respectively (P =.019). Median overall survival was 42 months (95% CI, not available) and 13 months (95% CI, 8.0-18.8) in the sorafenib cohort and in the intensive chemotherapy cohort, respectively (P =.026). The results were similar with censoring at the time of allogeneic stem cell transplantation.
The authors concluded that “the combination of sorafenib with intensive chemotherapy contributes to improved survival in patients with newly diagnosed, FLT3-ITD-mutated AML regardless of whether they later undergo [allogeneic stem cell transplantation].”
1. Sasaki K, Kantarjian HM, Kadia T, et al. Sorafenib plus intensive chemotherapy improves survival in patients with newly diagnosed, FLT3‐internal tandem duplication mutation-positive acute myeloid leukemia [published online July 16, 2019]. Cancer. doi:10.1002/cncr.32387