A phase II study of frontline paclitaxel/carboplatin/bevacizumab, paclitaxel/carboplatin/temsirolimus, or ixabepilone/carboplatin/bevacizumab in advanced/recurrent endometrial cancer

Carol Aghajanian; Virginia Filiaci; Don S Dizon; Jay W Carlson; Matthew A Powell; Angeles Alvarez Secord; Krishnansu S Tewari; David P Bender; David M O'Malley; Ashley Stuckey; JianJiong Gao; Fanny Dao; Robert A Soslow; Heather A Lankes; Kathleen Moore; Douglas A Levine

doi:10.1016/j.ygyno.2018.05.018

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A phase II study of frontline paclitaxel/carboplatin/bevacizumab, paclitaxel/carboplatin/temsirolimus, or ixabepilone/carboplatin/bevacizumab in advanced/recurrent endometrial cancer

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A phase II study of frontline paclitaxel/carboplatin/bevacizumab, paclitaxel/carboplatin/temsirolimus, or ixabepilone/carboplatin/bevacizumab in advanced/recurrent endometrial cancer

Carol Aghajanian, Virginia Filiaci, Don S Dizon, Jay W Carlson, Matthew A Powell, Angeles Alvarez Secord, Krishnansu S Tewari, David P Bender, David M O'Malley, Ashley Stuckey, …

Gynecologic Oncology, Vol.150(2), pp.274-281

08/2018

DOI: 10.1016/j.ygyno.2018.05.018

PMCID: PMC6179372

PMID: 29804638

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Abstract

Paclitaxel and carboplatin (PC) is a standard initial therapy for advanced endometrial cancer. We evaluated the efficacy and tolerability of incorporating three novel agents into initial therapy. In this randomized phase II trial, patients with chemotherapy-naïve stage III/IVA (with measurable disease) and stage IVB or recurrent (with or without measurable disease) endometrial cancer were randomly assigned to treatment with PC plus bevacizumab (Arm 1), PC plus temsirolimus (Arm 2) or ixabepilone and carboplatin (IC) plus bevacizumab (Arm 3). The primary endpoint was progression-free survival (PFS). Comparable patients on the PC Arm of trial GOG209 were used as historical controls. Secondary endpoints were response rate, overall survival (OS), and safety. Overall, 349 patients were randomized. PFS duration was not significantly increased in any experimental arm compared with historical controls (p > 0.039). Treatment HRs (92% CI) for Arms 1, 2, and 3 relative to controls were 0.81 (0.63–1.02), 1.22 (0.96–1.55) and 0.87 (0.68–1.11), respectively. Response rates were similar across arms (60%, 55% and 53%, respectively). Relative to controls, OS duration (with censoring at 36 months), was significantly increased in Arm 1 (p < 0.039) but not in Arms 2 and 3; the HRs (92% CIs) were 0.71 (0.55–0.91), 0.99 (0.78–1.26), and 0.97 (0.77–1.23), respectively. No new safety signals were identified. Common mutations and rates of mismatch repair protein loss are described by histotype. Potential predictive biomarkers for temsirolimus and bevacizumab were identified. PFS was not significantly increased in any experimental arm compared to historical controls. NRG Oncology/Gynecologic Oncology Group Study GOG-86P. •Paclitaxel + carboplatin is standard initial therapy for advanced endometrial cancer.•We assessed combinations with bevacizumab, temsirolimus or ixabepilone.•PFS was not significantly improved compared to historical control.

Endometrial Cancer

Carboplatin

Temsirolimus

Ixabepilone

Paclitaxel

Bevacizumab

Details

Title: Subtitle: A phase II study of frontline paclitaxel/carboplatin/bevacizumab, paclitaxel/carboplatin/temsirolimus, or ixabepilone/carboplatin/bevacizumab in advanced/recurrent endometrial cancer
Creators: Carol Aghajanian - Memorial Sloan Kettering Cancer Center and Weill Cornell Medical Center, New York, NY, United States
Virginia Filiaci - Department of Biostatics and Bioinformatics, Roswell Park Cancer Institute and NRG Oncology Buffalo Statistical and Data Management Center, Buffalo, NY, United States
Don S Dizon - Lifespan Cancer Institute/Rhode Island Hospital, Providence, RI, United States
Jay W Carlson - Cancer Research for the Ozarks, Springfield, MO, United States
Matthew A Powell - Washington University, St. Louis, MO, United States
Angeles Alvarez Secord - Duke University, Durham, NC, United States
Krishnansu S Tewari - University of California Irvine Medical Center, Orange, CA, United States
David P Bender - University of Iowa, Iowa City, IA, United States
David M O'Malley - Ohio State University Medical Center, James Cancer Center, Columbus, OH, United States
Ashley Stuckey - Women and Infants Hospital, Providence, RI, United States
JianJiong Gao
Fanny Dao - Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY, United States
Robert A Soslow - Memorial Sloan Kettering Cancer Center and Weill Cornell Medical Center, New York, NY, United States
Heather A Lankes - NRG Oncology Biospecimen Bank-Columbus, Biopathology Center, The Reseach Institue at Nationwide Children's Hospital, Columbus, OH, United States
Kathleen Moore - Stephenson Cancer Center and University of Oklahoma, Oklahoma City, OK, United States
Douglas A Levine - Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY, United States
Resource Type: Journal article
Publication Details: Gynecologic Oncology, Vol.150(2), pp.274-281
DOI: 10.1016/j.ygyno.2018.05.018
PMID: 29804638
PMCID: PMC6179372
NLM abbreviation: Gynecol Oncol
ISSN: 0090-8258
eISSN: 1095-6859
Publisher: Elsevier Inc
Grant note: 1 U10 CA180822 / NRG Oncology CA 37517 / Gynecologic Oncology Group Statistical Office U10 CA 27469 / National Cancer Institute (https://doi.org/10.13039/100000054) U24 CA196067 / NRG Oncology Biospecimen Bank P30 CA008748 / MSK Cancer Center 3 U10 CA027469-29S1 / ARRA U24 CA114793 / Gynecologic Oncology Group Tissue Bank U10 CA180868 / NRG Operations and Biospecimen Bank SU2C-AACR-DT0209 / Entertainment Industry Foundation (https://doi.org/10.13039/100006535)
Language: English
Date published: 08/2018
Academic Unit: Obstetrics and Gynecology
Record Identifier: 9983930968002771

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