Advertisement

Tale of Two FLT3 Inhibitors in AML: Gilteritinib and Quizartinib


Advertisement
Get Permission

Data supporting the use of FLT3 inhibitors in patients with acute myeloid leukemia (AML) were featured at the 2018 ASH Annual Meeting & Exposition. Gilteritinib was evaluated in combination with induction and consolidation as front-line therapy in newly diagnosed patients with AML,1 and quizartinib was compared with chemotherapy in the salvage setting.2 The U.S. Food and Drug Administration recently approved gilteritinib and granted Breakthrough Therapy designation for quizartinib, in the treatment of relapsed or refractory AML with FLT3 mutations.

Gilteritinib, as part of induction/consolidation therapy, yielded a composite complete response rate exceeding 90%, in a phase I trial in newly diagnosed patients.1 Single-agent quizartinib significantly (though somewhat modestly) prolonged survival over salvage chemotherapy in the phase III Quantum-R trial.2

Clinical Commentary

Steven Gore, MD, Professor of Medicine at Yale School of Medicine and Director of Hematologic Malignancies at Yale Cancer Center, New Haven, Connecticut, commented on the FLT3 inhibitor studies for The ASCO Post. He considered the findings from the phase I gilteritinib trial more interesting and encouraging than those for quizartinib in the Quantum-R trial.

Steven Gore, MD

Steven Gore, MD

“I think the results were disappointing for quizartinib,” he said. “It’s obviously good to have responses in relapsed patients, but they didn’t seem to impact the long-term outcomes in this study. The improvement in overall survival was small, and no one was cured. I’m disappointed that more patients were not salvaged curatively—at the end of the day, only 15% of patients were alive.”

With promising results shown for upfront treatment with gilteritinib, Dr. Gore maintained: “If anything, these findings increase the urgency for us to find the best upfront treatment for patients with FLT3-mutated AML and to get them to transplant in first remission—and not wait until the relapsed setting.”

Dr. Gore indicated that front-line studies are being conducted with both gilteritinib and quizartinib. 

DISCLOSURE: Dr. Gore has received research support from Astellas and Daiichi Sankyo, who sponsored these studies.

REFERENCES

1. Pratz KW, Cherry M, Altman JK, et al: Updated results from a phase 1 study of gilteritinib in combination with induction and consolidation chemotherapy in subjects with newly diagnosed acute myeloid leukemia. 2018 ASH Annual Meeting & Exposition. Abstract 564. Presented December 3, 2018.

2. Cortes JE, Khaled SK, Martinelli G, et al: Efficacy and safety of single-agent quizartinib, a potent and selective FLT3 inhibitor, in patients with FLT3-internal tandem duplication-mutated relapsed/refractory acute myeloid leukemia enrolled in the global, phase 3, randomized controlled Quantum-R trial. 2018 ASH Annual Meeting & Exposition. Abstract 563. Presented December 3, 2018.


Related Articles

Phase III Data Support Use of Gilteritinib in Relapsed or Refractory FLT3-Mutated AML

Treatment with gilteritinib, an oral type 1, FLT inhibitor, significantly improved overall survival compared with chemotherapy in patients with FLT3-positive relapsed or refractory acute myeloid leukemia (AML), according to the final results of the phase III ADMIRAL trial.1 The longest survival for ...

Expert Point of View: Tapan Kadia, MD, and Louis Weiner, MD

Tapan Kadia, MD

Tapan Kadia, MD

Louis L. Weiner, MD

Louis L. Weiner, MD

Commenting on the ADMIRAL trial, Tapan Kadia, MD, Associate Professor at MD Anderson Cancer Center in Houston, reminded the audience that the most important discovery with genetic sequencing is that acute myeloid leukemia (AML) is a group of...

Advertisement

Advertisement



;
Advertisement