TY - JOUR
T1 - A quality-adjusted survival time without symptoms or toxicities analysis of glasdegib plus low-dose cytarabine versus low-dose cytarabine as initial therapy for acute myeloid leukemia in patients who are not considered candidates for intensive chemotherapy
AU - Solem, Caitlyn T.
AU - Bell, Timothy J.
AU - Kwon, Youngmin
AU - Cappelleri, Joseph C.
AU - Johnson, Courtney
AU - Bhattacharyya, Helen
AU - Hoang, Caroline J.
AU - Cortes, Jorge E.
N1 - Funding Information:
Upon request and subject to certain criteria, conditions, and exceptions (see https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information), Pfizer will provide access to individual de-identified participant data from Pfizer-sponsored global interventional clinical studies conducted for medicines, vaccines, and medical devices 1) for indications that have been approved in the United States and/or the European Union or 2) in programs that have been terminated (ie, development for all indications has been discontinued). Pfizer will also consider requests for the protocol, data dictionary, and statistical analysis plan. Data may be requested from Pfizer trials 24?months after study completion. The de-identified participant data will be made available to researchers whose proposals meet the research criteria and other conditions, and for which an exception does not apply, via a secure portal. To gain access, data requestors must enter into a data access agreement with Pfizer. Caitlyn T. Solem is an employee of Pharmerit International, LP, which was paid to conduct the research herein. Timothy J. Bell, Joseph C. Cappelleri, Helen Bhattacharyya, and Caroline J. Hoang are employees of and stockholders in Pfizer, Inc. Youngmin Kwon and Courtney Johnson were employees of Pharmerit International, LP, at the time the research was conducted. Jorge E. Cortes reports grants and personal fees from Pfizer during the conduct of the study; grants and personal fees from Novartis, Takeda, Biopath Holdings, and Jazz outside the submitted work; and grants from Amphivena and Merus outside the submitted work. This study was funded by Pfizer, Inc. The University of Texas MD Anderson Cancer Center is supported by the National Institutes of Health (grant P30 CA016672).
Funding Information:
This study was funded by Pfizer, Inc. The University of Texas MD Anderson Cancer Center is supported by the National Institutes of Health (grant P30 CA016672).
Publisher Copyright:
© 2020 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - Background: In a randomized study, glasdegib (a hedgehog inhibitor) plus low-dose cytarabine (LDAC) significantly prolonged survival in comparison with LDAC in patients with acute myeloid leukemia (AML). A quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST) approach was used to evaluate comparative quality-adjusted survival. Methods: Overall survival was partitioned into the following: time with any treatment-emergent grade 3 or higher adverse events (TOX); time without symptoms of disease progression or toxicity (TWiST); and time after treatment discontinuation due to insufficient clinical response, relapse, or death time after progression (REL). Q-TWiST was calculated by multiplying the restricted mean time in each state by respective utilities and then summing up the utility-adjusted time. Results: At 20 months of follow-up, the survival probabilities for the glasdegib-LDAC arm and the LDAC arm were 28.2% and 7.9%, respectively. Glasdegib-LDAC patients (n = 78), in comparison with LDAC patients (n = 38), had significantly longer mean TWiST (+3.4 months; 95% confidence interval [CI], 1.8-5.2 months) and TOX (+0.8 months; 95% CI, 0.1-1.6 months) and longer but nonsignificant REL (+0.3 months; 95% CI, −1.9 to 2.3 months). Q-TWiST was 4.0 months (95% CI, 2.1-5.8 months) longer with glasdegib plus LDAC, and this translated into a 75% relative improvement in quality-adjusted survival with respect to LDAC. Results were robust to the length of follow-up (6-24 months) and remained significant when all adverse events, regardless of grade, were included. Conclusions: These results suggest that most of the survival benefit from glasdegib plus LDAC versus LDAC alone is TWiST, and this represents added time in relatively “good” health. These results support the clinical value of glasdegib plus LDAC as initial therapy for AML in patients for whom intensive chemotherapy is not an option.
AB - Background: In a randomized study, glasdegib (a hedgehog inhibitor) plus low-dose cytarabine (LDAC) significantly prolonged survival in comparison with LDAC in patients with acute myeloid leukemia (AML). A quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST) approach was used to evaluate comparative quality-adjusted survival. Methods: Overall survival was partitioned into the following: time with any treatment-emergent grade 3 or higher adverse events (TOX); time without symptoms of disease progression or toxicity (TWiST); and time after treatment discontinuation due to insufficient clinical response, relapse, or death time after progression (REL). Q-TWiST was calculated by multiplying the restricted mean time in each state by respective utilities and then summing up the utility-adjusted time. Results: At 20 months of follow-up, the survival probabilities for the glasdegib-LDAC arm and the LDAC arm were 28.2% and 7.9%, respectively. Glasdegib-LDAC patients (n = 78), in comparison with LDAC patients (n = 38), had significantly longer mean TWiST (+3.4 months; 95% confidence interval [CI], 1.8-5.2 months) and TOX (+0.8 months; 95% CI, 0.1-1.6 months) and longer but nonsignificant REL (+0.3 months; 95% CI, −1.9 to 2.3 months). Q-TWiST was 4.0 months (95% CI, 2.1-5.8 months) longer with glasdegib plus LDAC, and this translated into a 75% relative improvement in quality-adjusted survival with respect to LDAC. Results were robust to the length of follow-up (6-24 months) and remained significant when all adverse events, regardless of grade, were included. Conclusions: These results suggest that most of the survival benefit from glasdegib plus LDAC versus LDAC alone is TWiST, and this represents added time in relatively “good” health. These results support the clinical value of glasdegib plus LDAC as initial therapy for AML in patients for whom intensive chemotherapy is not an option.
KW - acute myeloid leukemia
KW - glasdegib
KW - low-dose cytarabine
KW - quality of life
KW - quality-adjusted survival
KW - quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST)
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U2 - 10.1002/cncr.33072
DO - 10.1002/cncr.33072
M3 - Article
C2 - 32697335
AN - SCOPUS:85088293885
VL - 126
SP - 4315
EP - 4321
JO - Cancer
JF - Cancer
SN - 0008-543X
IS - 19
ER -