The addition of sorafenib to intensive chemotherapy had a significant impact on the survival rate of patients with FLT3-internal tandem duplication mutation-positive acute myeloid leukemia.
The addition of sorafenib to intensive chemotherapy more than tripled the median overall survival of patients with newly diagnosed, FLT3-internal tandem duplication (FLT3-ITD) mutation-positive acute myeloid leukemia (AML), according to the results of a study published in Cancer.
With a median follow-up of 49.5 months, the median overall survival was 42 months for patients given sorafenib plus intensive chemotherapy compared with 13 months of chemotherapy alone (P=.026).
“Because the median duration of sorafenib was 4.6 months, the survival benefit of our study likely derived from the addition of sorafenib to induction and consolidation therapy, whether or not patients underwent autologous stem cell transplant (ASCT),” wrote Koji Sasaki, MD, of The University of Texas MD Anderson Cancer Center, and colleagues.
The retrospective study looked at 183 patients with newly diagnosed, FLT3-ITD AML between February 2001 and December 2017. Patients were treated with intensive chemotherapy plus sorafenib (43%) or intensive chemotherapy alone (57%). Propensity score matching identified 42 patients in each cohort.
“Before propensity score matching, significant imbalances were observed in patient characteristics, including the addition of a purine analogue, between the cohorts,” the researchers wrote. “These imbalances were minimized without significant differences after propensity score matching, and the cohorts were optimized for the comparison of treatment between cohorts.”
After propensity score matching, the overall response rate was numerically higher in the sorafenib group compared with intensive chemotherapy alone (98% vs 83%; P=.057), but did not show a significant increase. This improvement in response translated into improvements in survival, according to the researchers.
Event-free survival was significantly improved with sorafenib, with a median length almost four times as long as chemotherapy alone (35 vs 8 months; P=.019).
“Whether or not patients were eligible for ASCT, even those who did not undergo ASCT saw improved event-free survival and overall survival with the addition of sorafenib to the intensive therapy regimen,” the researchers noted.
With censoring at the time of transplant, the median event-free survival was 31 months compared with 8 months in the intensive chemotherapy group (P=.031), and overall survival was not yet reached for sorafenib compared with 10 months for chemotherapy alone (P=.001).
The researchers conducted a backward multivariate Cox proportional hazard model with time to transplant as a time-dependent co-variate and found that therapy with sorafenib was an independent prognostic factors for overall survival (P=.009; hazard ratio=0.558; 95% CI, 0.360–0.865).
“Given the paucity of randomized clinical trials in patients with newly diagnosed, FLT3-ITD–mutated AML, the results of our propensity score analysis provide preliminary evidence that the addition of sorafenib to intensive chemotherapy regimens can improve outcomes, including survival, among these patients,” the researchers concluded.