TY - JOUR
T1 - Interim analysis of the phase II study
T2 - Noninferiority study of doxorubicin with upfront dexrazoxane plus olaratumab for advanced or metastatic soft-tissue Sarcoma A C
AU - van Tine, Brian A.
AU - Hirbe, Angela C.
AU - Oppelt, Peter
AU - Frith, Ashley E.
AU - Rathore, Richa
AU - Mitchell, Joshua D.
AU - Wan, Fei
AU - Berry, Shellie
AU - Landeau, Michele
AU - Heberton, George A.
AU - Gorcsan, John
AU - Huntjens, Peter R.
AU - Soyama, Yoku
AU - Vader, Justin M.
AU - Alvarez-Cardona, Jose A.
AU - Zhang, Kathleen W.
AU - Lenihan, Daniel J.
AU - Krone, Ronald J.
N1 - Funding Information:
Financial support was provided by a grant from the Richard & Marie Hahn Cancer Medical Research Endowment Fund at the Barnes Jewish Foundation, a gift from
Funding Information:
Financial support was provided by a grant from the Richard & Marie Hahn Cancer Medical Research Endowment Fund at the Barnes Jewish Foundation, a gift from Donald and Shirley Sher, divisional funding from the Division of Medical Oncology provided by John D DiPersio, STL Cure Sarcoma 6K, and by the National Center for Advancing Translational Sciences of the NIH under Award Number UL1TR002345 (J.D. Mitchell). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Publisher Copyright:
© 2021 American Association for Cancer Research.
PY - 2021/7/15
Y1 - 2021/7/15
N2 - Purpose: To report the interim analysis of the phase II single-arm noninferiority trial, testing the upfront use of dexrazoxane with doxorubicin on progression-free survival (PFS) and cardiac function in soft-tissue sarcoma (STS). Patients and Methods: Patients with metastatic or unresectable STS who were candidates for first-line treatment with doxorubicin were deemed eligible. An interim analysis was initiated after 33 of 65 patients were enrolled. Using the historical control of 4.6 months PFS for doxorubicin in the front-line setting, we tested whether the addition of dexrazoxane affected the efficacy of doxorubicin in STS. The study was powered so that a decrease of PFS to 3.7 months would be considered noninferior. Secondary aims included cardiac-related mortality, incidence of heart failure/cardiomyopathy, and expansion of cardiac monitoring parameters including three-dimensional echocardiography. Patients were allowed to continue on doxorubicin beyond 600 mg/m2 if they were deriving benefit and were not demonstrating evidence of symptomatic cardiac dysfunction. Results: At interim analysis, upfront use of dexrazoxane with doxorubicin demonstrated a PFS of 8.4 months (95% confidence interval: 5.1–11.2 months). Only 3 patients were removed from study for cardiotoxicity, all on > 600 mg/m2 doxorubicin. No patients required cardiac hospitalization or had new, persistent cardiac dysfunction with left ventricular ejection fraction remaining below 50%. The median administered doxorubicin dose was 450 mg/m2 (interquartile range, 300–750 mg/m2). Conclusions: At interim analysis, dexrazoxane did not reduce PFS in patients with STS treated with doxorubicin. Involvement of cardio-oncologists is beneficial for the monitoring and safe use of high-dose anthracyclines in STS.
AB - Purpose: To report the interim analysis of the phase II single-arm noninferiority trial, testing the upfront use of dexrazoxane with doxorubicin on progression-free survival (PFS) and cardiac function in soft-tissue sarcoma (STS). Patients and Methods: Patients with metastatic or unresectable STS who were candidates for first-line treatment with doxorubicin were deemed eligible. An interim analysis was initiated after 33 of 65 patients were enrolled. Using the historical control of 4.6 months PFS for doxorubicin in the front-line setting, we tested whether the addition of dexrazoxane affected the efficacy of doxorubicin in STS. The study was powered so that a decrease of PFS to 3.7 months would be considered noninferior. Secondary aims included cardiac-related mortality, incidence of heart failure/cardiomyopathy, and expansion of cardiac monitoring parameters including three-dimensional echocardiography. Patients were allowed to continue on doxorubicin beyond 600 mg/m2 if they were deriving benefit and were not demonstrating evidence of symptomatic cardiac dysfunction. Results: At interim analysis, upfront use of dexrazoxane with doxorubicin demonstrated a PFS of 8.4 months (95% confidence interval: 5.1–11.2 months). Only 3 patients were removed from study for cardiotoxicity, all on > 600 mg/m2 doxorubicin. No patients required cardiac hospitalization or had new, persistent cardiac dysfunction with left ventricular ejection fraction remaining below 50%. The median administered doxorubicin dose was 450 mg/m2 (interquartile range, 300–750 mg/m2). Conclusions: At interim analysis, dexrazoxane did not reduce PFS in patients with STS treated with doxorubicin. Involvement of cardio-oncologists is beneficial for the monitoring and safe use of high-dose anthracyclines in STS.
UR - http://www.scopus.com/inward/record.url?scp=85110069652&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-20-4621
DO - 10.1158/1078-0432.CCR-20-4621
M3 - Article
C2 - 33766818
AN - SCOPUS:85110069652
SN - 1078-0432
VL - 27
SP - 3854
EP - 3860
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 14
ER -