TY - JOUR
T1 - Prospective evaluation of doxorubicin cardiotoxicity in patients with advanced soft-tissue sarcoma treated in the ANNOUNCE Phase III randomized trial A C
AU - Jones, Robin L.
AU - Wagner, Andrew J.
AU - Kawai, Akira
AU - Tamura, Kazuo
AU - Shahir, Ashwin
AU - van Tine, Brian A.
AU - Martín-Broto, Javier
AU - Peterson, Patrick M.
AU - Wright, Jennifer
AU - Tap, William D.
N1 - Funding Information:
R.L. Jones reports personal fees from Eli Lilly during the conduct of the study, and personal fees from Adaptimmune, Athenex, Bayer, Boehringer Ingelheim, Blueprint, Clinigen, Eisai, Epizyme, Daiichi Sankyo, Deciphera, Immune Design, Merck, PharmaMar, SpringWorks, TRACON, and Upto Date outside the submitted work. A.J. Wagner reports grants and personal fees from Eli Lilly during the conduct of the study; grants and personal fees from Deciphera, Daiichi Sankyo, and Five Prime Therapeutics, personal fees from Mundipharma, Nanocarrier, and Epizyme, and grants from Plexxikon and Karyopharm outside the submitted work. A. Kawai reports personal fees from Novartis, Taiho, Eli Lilly, Eisai, Takara, and Otsuka outside the submitted work. K. Tamura reports personal fees from Eli Lilly during the conduct of the study, and personal fees from Ono Pharmaceutical Co., Eisai Co., and Asahi Kasei Pharma outside the submitted work. A. Shahir is an employee and stockholder of Eli Lilly and Company during the conduct of the study and outside the submitted work. B.A. Van Tine reports personal fees from Epizyme, Eli Lilly, Apexigen, and Deciphera Pharm, grants, personal fees, and other from GlaxoSmithKline, grants and personal fees from Pfizer, grants from Merck and TRACON, and other from Accuronix Therapeutics outside the submitted work. J. Martin Broto reports grants and personal fees from Eli Lilly during the conduct of the study, grants and personal fees from Eisai, PharmaMar, and Bayer and grants from Immix Bio-Pharma, Novartis, Adaptimmune, AROG, Lixte, Karyopharm, Deciphera, GlaxoSmithKline, Blueprint, Nektar, Forma, Amgen, and Daiichi Sankyo outside the submitted work. P.M. Peterson is an employee of Eli Lilly and Company. J. Wright is an employee and stockholder of Eli Lilly and Company during the conduct of the study. W.D. Tap reports grants and personal fees from Eli Lilly and Company during the conduct of the study; grants and personal fees from EMD Serono, Eisai, Mundipharma, C4 Therapeutics, Daiichi Sankyo, Blueprint, GlaxoSmithKline, Agios Pharmaceuticals, Nanocarrier, and Deciphera outside the submitted work; has a patent for companion diagnostic for CDK4 inhibitors - 14/ 854,329 pending to MSK/SKI and enigma and CDH18 as companion diagnostics for CDK4 inhibition - SKI2016-021-03 pending to MSK/SLI; has scientific advisory board membership with Certis Oncology Solutions; is cofounder at and has stock ownership with Atropos Therapeutics; and has stock ownership and scientific advisory board membership with and Innova Therapeutics.
Funding Information:
This study was funded by Eli Lilly and Company. W.D. Tap was funded, in part, through NIH/NCI Cancer Center Support grant P30 CA008748. Medical
Publisher Copyright:
© 2021 American Association for Cancer Research.
PY - 2021/7/15
Y1 - 2021/7/15
N2 - Purpose: Few prospective studies have assessed anthracycline-associated cardiotoxicity in patients with sarcoma. We evaluated cardiotoxicity in patients with soft-tissue sarcomas administered doxorubicin in the phase III ANNOUNCE trial (NCT02451943). Patients and Methods: Patients were anthracycline-na€ive adults with locally advanced or metastatic disease and left ventricular ejection fraction (LVEF) ≥50%. Patients could receive eight cycles of doxorubicin at 75 mg/m2. The cardioprotectant, dexrazoxane, was allowed at investigator discretion. Symptomatic cardiac adverse events (AEs) were recorded using Medical Dictionary for Regulatory Activities and graded using Common Terminology Criteria for Adverse Events 4.0. LVEF deterioration was measured by echocardiogram or multigated acquisition scan, defined as a decrease to <50%, or decrease from baseline value >10%. Results: A total of 504 patients received ≥1 cycles of doxorubicin [median cumulative dose, 450.3 mg/m2 (range, 72.3–634.0)]. Median follow-up of cardiac AEs was 28 weeks. Dexrazoxane was coadministered more frequently to patients receiving higher cumulative doxorubicin doses (38.6% receiving <450 mg/m2, 88.5% receiving 450–<600 mg/m2, and 90% receiving ≥600 mg/m2) and did not affect treatment efficacy. LVEF deterioration was seen in 62 of 153 (40.5%) patients who received a cumulative dose <450 mg/m2, 82 of 159 patients (51.6%) who received 450–<600 mg/m2, and 50 of 89 patients (56.2%) who received ≥600 mg/m2. Grade ≥3 cardiac dysfunction occurred in 2% of patients at <450 mg/m2, 3% at 450–<600 mg/m2, and 1.1% at ≥600 mg/m2. Incidence of treatment-related cardiac AEs was low across all dose ranges. Conclusions: Although follow-up was short, these results suggest doxorubicin can be administered at high cumulative doses (>450 mg/m2), with a low rate of cardiotoxicities, in the context of dexrazoxane coadministration.
AB - Purpose: Few prospective studies have assessed anthracycline-associated cardiotoxicity in patients with sarcoma. We evaluated cardiotoxicity in patients with soft-tissue sarcomas administered doxorubicin in the phase III ANNOUNCE trial (NCT02451943). Patients and Methods: Patients were anthracycline-na€ive adults with locally advanced or metastatic disease and left ventricular ejection fraction (LVEF) ≥50%. Patients could receive eight cycles of doxorubicin at 75 mg/m2. The cardioprotectant, dexrazoxane, was allowed at investigator discretion. Symptomatic cardiac adverse events (AEs) were recorded using Medical Dictionary for Regulatory Activities and graded using Common Terminology Criteria for Adverse Events 4.0. LVEF deterioration was measured by echocardiogram or multigated acquisition scan, defined as a decrease to <50%, or decrease from baseline value >10%. Results: A total of 504 patients received ≥1 cycles of doxorubicin [median cumulative dose, 450.3 mg/m2 (range, 72.3–634.0)]. Median follow-up of cardiac AEs was 28 weeks. Dexrazoxane was coadministered more frequently to patients receiving higher cumulative doxorubicin doses (38.6% receiving <450 mg/m2, 88.5% receiving 450–<600 mg/m2, and 90% receiving ≥600 mg/m2) and did not affect treatment efficacy. LVEF deterioration was seen in 62 of 153 (40.5%) patients who received a cumulative dose <450 mg/m2, 82 of 159 patients (51.6%) who received 450–<600 mg/m2, and 50 of 89 patients (56.2%) who received ≥600 mg/m2. Grade ≥3 cardiac dysfunction occurred in 2% of patients at <450 mg/m2, 3% at 450–<600 mg/m2, and 1.1% at ≥600 mg/m2. Incidence of treatment-related cardiac AEs was low across all dose ranges. Conclusions: Although follow-up was short, these results suggest doxorubicin can be administered at high cumulative doses (>450 mg/m2), with a low rate of cardiotoxicities, in the context of dexrazoxane coadministration.
UR - http://www.scopus.com/inward/record.url?scp=85110242628&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-20-4592
DO - 10.1158/1078-0432.CCR-20-4592
M3 - Article
C2 - 33632930
AN - SCOPUS:85110242628
SN - 1078-0432
VL - 27
SP - 3861
EP - 3866
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 14
ER -