Beyond Survival: A Quality-Adjusted Analysis of Glasdegib in AML
Posted: Monday, November 16, 2020
In reportedly the first quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST) analysis performed in adults 65 years old or older with acute myeloid leukemia (AML), the Hedgehog inhibitor glasdegib plus low-dose cytarabine yielded clinically significant survival benefits over low-dose cytarabine alone. Conducting a secondary post hoc analysis from the phase II BRIGHT AML 1003 trial, Jorge E. Cortes, MD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues supported the therapeutic benefit of this combination regimen for newly diagnosed patients with AML who are not eligible for intensive therapy. These findings were published in Cancer.
“The majority of the additional survival time that glasdegib-low-dose cytarabine patients experienced was time without symptoms of disease progression or toxicity, which represented added time in relatively ‘good’ health,” the investigators concluded.
This secondary analysis used data from the AML cohort of the BRIGHT AML 1003 trial, where 116 patients were assigned in a 2:1 ratio to receive low-dose cytarabine or glasdegib plus low-dose cytarabine. Survival time was stratified into three categories: time with any treatment-emergent grade 3 or higher adverse events, time without symptoms of disease progression or toxicity (TWIST), and time after treatment cessation from lack of clinical response, relapse, or death.
Although BRIGHT AML 1003 reported a survival benefit with glasdegib plus low-dose cytarabine, this analysis further noted that the quality-adjusted survival difference of the glasdegib therapy was 4.0 months—a 75% relative gain in quality-adjusted survival compared with the overall survival of patients treated with low-dose cytarabine alone. Subgroup analysis revealed Q-TWiST gains of 2.9 months for patients 75 years or older, 6.5 months for patients with an Eastern Cooperative Oncology Group performance status of at least 2, and 6.0 for patients with secondary AML.
Disclosure: For full disclosures of the study authors, visit onlinelibrary.wiley.com.