TY - JOUR
T1 - Randomized Phase III Trial of Paclitaxel and Carboplatin Versus Paclitaxel and Ifosfamide in Patients With Carcinosarcoma of the Uterus or Ovary
T2 - An NRG Oncology Trial
AU - Powell, Matthew A.
AU - Filiaci, Virginia L.
AU - Hensley, Martee L.
AU - Huang, Helen Q.
AU - Moore, Kathleen N.
AU - Tewari, Krishnansu S.
AU - Copeland, Larry J.
AU - Secord, Angeles A.
AU - Mutch, David G.
AU - Santin, Alessandro
AU - Warshal, David P.
AU - Spirtos, Nick M.
AU - DiSilvestro, Paul A.
AU - Ioffe, Olga B.
AU - Miller, David S.
N1 - Publisher Copyright:
© 2022 American Society of Clinical Oncology. All rights reserved.
PY - 2022/3/20
Y1 - 2022/3/20
N2 - PURPOSE This phase III randomized trial (NCT00954174) tested the null hypothesis that paclitaxel and carboplatin (PC) is inferior to paclitaxel and ifosfamide (PI) for treating uterine carcinosarcoma (UCS). PATIENTS AND METHODS Adults with chemotherapy-naive UCS or ovarian carcinosarcoma (OCS) were randomly assigned to PC or PI with 3-week cycles for 6-10 cycles. With 264 events in patients with UCS, the power for an overall survival (OS) hybrid noninferiority design was 80% for a null hazard ratio (HR) of 1.2 against a 13% greater death rate on PI with a type I error of 5% for a one-tailed test. RESULTS The study enrolled 536 patients with UCS and 101 patients with OCS, with 449 and 90 eligible, respectively. Primary analysis was on patients with UCS, distributed as follows: 40% stage I, 6% stage II, 31% stage III, 15% stage IV, and 8% recurrent. Among eligible patients with UCS, PC was assigned to 228 and PI to 221. PC was not inferior to PI. The median OS was 37 versus 29 months (HR 5 0.87; 90% CI, 0.70 to 1.075; P,<01 for noninferiority, P<1 for superiority). The median progression-free survival was 16 versus 12 months (HR 5 0.73; P = , 0.01 for noninferiority, P <.01 for superiority). Toxicities were similar, except that more patients in the PC arm had hematologic toxicity and more patients in the PI arm had confusion and genitourinary hemorrhage. Among 90 eligible patients with OCS, those in the PC arm had longer OS (30 v 25 months) and progression-free survival (15 v 10 months) than those in the PI arm, but with limited precision, these differences were not statistically significant. CONCLUSION PC was not inferior to the active regimen PI and should be standard treatment for UCS.
AB - PURPOSE This phase III randomized trial (NCT00954174) tested the null hypothesis that paclitaxel and carboplatin (PC) is inferior to paclitaxel and ifosfamide (PI) for treating uterine carcinosarcoma (UCS). PATIENTS AND METHODS Adults with chemotherapy-naive UCS or ovarian carcinosarcoma (OCS) were randomly assigned to PC or PI with 3-week cycles for 6-10 cycles. With 264 events in patients with UCS, the power for an overall survival (OS) hybrid noninferiority design was 80% for a null hazard ratio (HR) of 1.2 against a 13% greater death rate on PI with a type I error of 5% for a one-tailed test. RESULTS The study enrolled 536 patients with UCS and 101 patients with OCS, with 449 and 90 eligible, respectively. Primary analysis was on patients with UCS, distributed as follows: 40% stage I, 6% stage II, 31% stage III, 15% stage IV, and 8% recurrent. Among eligible patients with UCS, PC was assigned to 228 and PI to 221. PC was not inferior to PI. The median OS was 37 versus 29 months (HR 5 0.87; 90% CI, 0.70 to 1.075; P,<01 for noninferiority, P<1 for superiority). The median progression-free survival was 16 versus 12 months (HR 5 0.73; P = , 0.01 for noninferiority, P <.01 for superiority). Toxicities were similar, except that more patients in the PC arm had hematologic toxicity and more patients in the PI arm had confusion and genitourinary hemorrhage. Among 90 eligible patients with OCS, those in the PC arm had longer OS (30 v 25 months) and progression-free survival (15 v 10 months) than those in the PI arm, but with limited precision, these differences were not statistically significant. CONCLUSION PC was not inferior to the active regimen PI and should be standard treatment for UCS.
UR - http://www.scopus.com/inward/record.url?scp=85126642101&partnerID=8YFLogxK
U2 - 10.1200/JCO.21.02050
DO - 10.1200/JCO.21.02050
M3 - Article
C2 - 35007153
AN - SCOPUS:85126642101
SN - 0732-183X
VL - 40
SP - 968
EP - 977
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 9
ER -