Discussion
AML
This randomized phase 3 trial in patients with untreated AML found that the addition of glasdegib versus placebo to cytarabine and daunorubicin or azacitidine therapy did not significantly improve OS, and the primary efficacy endpoint for the BRIGHT AML 1019 phase 3 trial was not met. The results of this trial emphasize the importance of phase 3 confirmatory studies, and of conducting those studies in heterogenous populations.In the non-intensive study, adding glasdegib to azacitidine resulted in a numerically higher rate of CR compared with azacitidine alone, and the probability of achieving CRThe phase 2 BRIGHT AML 1003 trial also revealed a survival benefit with glasdegib added to LDAC versus LDAC alone [The overall safety profile of glasdegib plus cytarabine and daunorubicin or azacitidine was consistent with the known safety profiles of these agents. The overall rate of TEAEs, grade 3/4 TEAEs, and serious TEAEs was generally similar between treatment arms in the intensive and non-intensive studies.In the intensive study, In conclusion, this study found the addition of glasdegib to either cytarabine and daunorubicin or azacitidine therapy did not significantly improve OS, and the primary endpoint for the BRIGHT AML 1019 phase 3 trial was not met. These results are in contrast with favorable results previously observed with glasdegib in combination with LDAC compared with LDAC alone [