The addition of paclitaxel to doxorubicin and cisplatin and volume-directed radiation does not improve overall survival (OS) or long-term recurrence-free survival (RFS) in advanced endometrial cancer (EC): A randomized phase III NRG/Gynecologic Oncology Group (GOG) study

Nick M. Spirtos; Danielle Enserro; Howard D. Homesley; Susan K. Gibbons; David Cella; Robert T. Morris; Koen DeGeest; Roger B. Lee; David S. Miller

doi:10.1016/j.ygyno.2019.03.240

The addition of paclitaxel to doxorubicin and cisplatin and volume-directed radiation does not improve overall survival (OS) or long-term recurrence-free survival (RFS) in advanced endometrial cancer (EC): A randomized phase III NRG/Gynecologic Oncology Group (GOG) study

Nick M. Spirtos
, Danielle Enserro
, Howard D. Homesley
, Susan K. Gibbons
, David Cella
, Robert T. Morris
, Koen DeGeest
, Roger B. Lee
, David S. Miller

Obstetrics and Gynecology

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Objectives: To determine if the addition of paclitaxel (P) to cisplatin and doxorubicin (CD) following surgical debulking and volume-directed radiation therapy improved long-term, recurrence-free survival (RFS) and overall survival (OS) in patients with advanced-stage endometrial cancer (EC). Methods: Prospective, randomized GOG trial comparing (CD) (50 mg/m²)/(45 mg/m²) +/− (P) (160 mg/m²) following volume-directed radiation and surgery in advanced EC. A Kaplan-Meier (KM) analysis characterized the relationship between treatment arms and the OS outcome, a log-rank test assessed the independence of treatment with the OS outcome, and the treatment effect on estimated OS was determined using a Cox proportional hazards (PH) model stratified by stage. The PH assumption was assessed using a test of interaction between treatment variable and the natural logarithm of survival time. Adverse events, regardless of attribution, were graded. Results: Since initial publication, 60 deaths occurred, leaving 311 patients alive with 290 (93.8%) recurrence- free. There was no significant decrease in the risk of recurrence or death associated with the CDP treatment regimen stratified for stage (p = 0.14, one-tail). The exploratory analysis for OS and the corresponding homogeneity tests for different effects across subgroups revealed only EFRT and EFRT & GRD status to have significantly different treatment effects (p = 0.027 and p = 0.017, respectively). Second primary malignancies were identified in 17/253 (6.4%) and 19/263 (7.0%) of patients treated with CD and CDP respectively. Breast (2.4%) followed by colon (1%) were the two cancers most frequently diagnosed in this setting. Conclusion: No significant difference between treatment arms was identified. Subgroup analysis both in the initial and current reports demonstrated a trend towards improved RFS and OS in patients treated with CDP and EFRT. This long-term analysis of outcomes also identified the necessity of providing on-going cancer screening to patients enrolled in trials.

Original language	English (US)
Pages (from-to)	13-21
Number of pages	9
Journal	Gynecologic oncology
Volume	154
Issue number	1
DOIs	https://doi.org/10.1016/j.ygyno.2019.03.240
State	Published - Jul 2019

Funding

Dr. Danielle Enserro receives money to her institution from NCI for Cooperative Group/NCTN Grant Funding for all aspects of this trial, including travel to Group meetings; statistical analysis, study monitoring, etc. She also receives monies from a NCTN Group Funding Grant through NCI, as well as monies from the GOG Foundation, Inc. This study was supported by National Cancer Institute grants to the Gynecologic Oncology Group (GOG) Administrative Office (CA 27469), the Gynecologic Oncology Group Statistical Office (CA 37517), NRG Oncology (1 U10 CA180822), NRG Operations (U10CA180868) and UG1CA189867 (NCORP). The following Gynecologic Oncology institutions participated in this study: Women's Cancer Center of Nevada, Ohio State University Comprehensive Cancer Center, MD Anderson Cancer Center, University of Iowa Hospitals and Clinics, Tacoma General Hospital, University of Oklahoma Health Sciences Center, University of Minnesota Medical Center-Fairview, University of California Medical Center at Irvine-Orange Campus, Washington University School of Medicine, Case Western Reserve University, Indiana University Hospital/Melvin and Bren Simon Cancer Center, Stony Brook University Medical Center, Walter Reed National Military Medical Center, Gynecologic Oncology Network/Brody School of Medicine, University of Massachusetts Memorial Health Care, University of Kentucky, Ellis Fischel Cancer Center, Cleveland Clinic Foundation, University of Colorado Cancer Center ? Anschutz Cancer Pavilion, Mayo Clinic, University of Mississippi Medical Center, Fred Hutchinson Cancer Research Center, Abramson Cancer Center of the University of Pennsylvania, Albany Medical College, Memorial Sloan Kettering Cancer Center, Abington Memorial Hospital, Duke University Medical Center, Cooper Hospital University Medical Center, ECOG Statistical Center, Wake Forest University Health Sciences, Moffitt Cancer Center and Research Institute, Wayne State University/Karmanos Cancer Institute, University of North Carolina at Chapel Hill, University of Texas Southwestern Medical Center, State University of New York Downstate Medical Center, Roswell Park Comprehensive Cancer Center, University of Cincinnati, Cancer Research for the Ozarks NCORP, Penn State Milton S. Hershey Medical Center, Tufts-New England Medical Center, Community Clinical Oncology Program, Thomas Jefferson University Hospital, Northern Indiana Cancer Research Consortium, University of Virginia, University of Chicago, Fletcher Allen Health Care, Cancer Research Consortium of West Michigan NCORP, University of Alabama at Birmingham, University of Pittsburgh Cancer Institute, University of New Mexico, Fox Chase Cancer Center, Yale University, University of Texas ? Galveston, University of Hawaii, Missouri Valley Cancer Consortium CCOP, Metro-Minnesota CCOP, Geisinger Medical Center and Central Illinois CCOP. Dr. David Miller served as a consultant for Tesaro, Janssen, Clovis and Genentech. His institution also received grant funding through Advenchen, Takeda, Tesaro and Xenetic. He also received monies from Genentech and Clovis for payment for lectures, including service on speakers' bureaus.

Funders	Funder number
Cancer Research for the Ozarks NCORP
Cooper Hospital University Medical Center
Ellis Fischel Cancer Center
GOG Foundation, Inc.
Gynecologic Oncology Group Statistical Office
Gynecologic Oncology Network/Brody School of Medicine, University of Massachusetts
Indiana University Hospital/Melvin
NCORP
NRG Oncology
NRG Operations
Northern Indiana Cancer Research Consortium
Ohio State University Comprehensive Cancer Center
Penn State Milton S. Hershey Medical Center
Tacoma General Hospital
University Iowa Hospitals and Clinics
Wayne State University/Karmanos Cancer Institute
Women's Cancer Center of Nevada
Yale University, University of Texas ?
National Institute of Health-National Cancer Institute	CA 37517, CA 27469, U10CA180868, UG1CA189867, 1 U10 CA180822, P30CA022453
H Lee Moffitt Cancer Center and Research Institute
New Mexico State University
University of Chicago and NorthShore University HealthSystem
The Cleveland Clinic Foundation
University of Texas M.D. Anderson Cancer Center
University Kentucky
University of North Carolina at Chapel Hill
University of Texas Southwestern University Medical Center
Oklahoma University Health Sciences Center
Department of Emergency Medicine University, Cincinnati Medical Center Cincinnati
Case-Western Reserve University
Virginia Commonwealth University
Neurology, Thomas Jefferson University
University of Pittsburgh Cancer Institute
SUNY-Downstate Medical Center
University of Colorado Colorado Springs

Keywords

Advanced endometrial cancer
Chemotherapy and radiation
Long-term follow-up
Optimal surgery

ASJC Scopus subject areas

Oncology
Obstetrics and Gynecology

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Spirtos, N. M., Enserro, D., Homesley, H. D., Gibbons, S. K., Cella, D., Morris, R. T., DeGeest, K., Lee, R. B., & Miller, D. S. (2019). The addition of paclitaxel to doxorubicin and cisplatin and volume-directed radiation does not improve overall survival (OS) or long-term recurrence-free survival (RFS) in advanced endometrial cancer (EC): A randomized phase III NRG/Gynecologic Oncology Group (GOG) study. Gynecologic oncology, 154(1), 13-21. https://doi.org/10.1016/j.ygyno.2019.03.240

The addition of paclitaxel to doxorubicin and cisplatin and volume-directed radiation does not improve overall survival (OS) or long-term recurrence-free survival (RFS) in advanced endometrial cancer (EC): A randomized phase III NRG/Gynecologic Oncology Group (GOG) study. / Spirtos, Nick M.; Enserro, Danielle; Homesley, Howard D. et al.
In: Gynecologic oncology, Vol. 154, No. 1, 07.2019, p. 13-21.

Research output: Contribution to journal › Article › peer-review

Spirtos, NM, Enserro, D, Homesley, HD, Gibbons, SK, Cella, D, Morris, RT, DeGeest, K, Lee, RB & Miller, DS 2019, 'The addition of paclitaxel to doxorubicin and cisplatin and volume-directed radiation does not improve overall survival (OS) or long-term recurrence-free survival (RFS) in advanced endometrial cancer (EC): A randomized phase III NRG/Gynecologic Oncology Group (GOG) study', Gynecologic oncology, vol. 154, no. 1, pp. 13-21. https://doi.org/10.1016/j.ygyno.2019.03.240

Spirtos NM, Enserro D, Homesley HD, Gibbons SK, Cella D, Morris RT et al. The addition of paclitaxel to doxorubicin and cisplatin and volume-directed radiation does not improve overall survival (OS) or long-term recurrence-free survival (RFS) in advanced endometrial cancer (EC): A randomized phase III NRG/Gynecologic Oncology Group (GOG) study. Gynecologic oncology. 2019 Jul;154(1):13-21. doi: 10.1016/j.ygyno.2019.03.240

Spirtos, Nick M. ; Enserro, Danielle ; Homesley, Howard D. et al. / The addition of paclitaxel to doxorubicin and cisplatin and volume-directed radiation does not improve overall survival (OS) or long-term recurrence-free survival (RFS) in advanced endometrial cancer (EC) : A randomized phase III NRG/Gynecologic Oncology Group (GOG) study. In: Gynecologic oncology. 2019 ; Vol. 154, No. 1. pp. 13-21.

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title = "The addition of paclitaxel to doxorubicin and cisplatin and volume-directed radiation does not improve overall survival (OS) or long-term recurrence-free survival (RFS) in advanced endometrial cancer (EC): A randomized phase III NRG/Gynecologic Oncology Group (GOG) study",

abstract = "Objectives: To determine if the addition of paclitaxel (P) to cisplatin and doxorubicin (CD) following surgical debulking and volume-directed radiation therapy improved long-term, recurrence-free survival (RFS) and overall survival (OS) in patients with advanced-stage endometrial cancer (EC). Methods: Prospective, randomized GOG trial comparing (CD) (50 mg/m2)/(45 mg/m2) +/− (P) (160 mg/m2) following volume-directed radiation and surgery in advanced EC. A Kaplan-Meier (KM) analysis characterized the relationship between treatment arms and the OS outcome, a log-rank test assessed the independence of treatment with the OS outcome, and the treatment effect on estimated OS was determined using a Cox proportional hazards (PH) model stratified by stage. The PH assumption was assessed using a test of interaction between treatment variable and the natural logarithm of survival time. Adverse events, regardless of attribution, were graded. Results: Since initial publication, 60 deaths occurred, leaving 311 patients alive with 290 (93.8\%) recurrence- free. There was no significant decrease in the risk of recurrence or death associated with the CDP treatment regimen stratified for stage (p = 0.14, one-tail). The exploratory analysis for OS and the corresponding homogeneity tests for different effects across subgroups revealed only EFRT and EFRT \& GRD status to have significantly different treatment effects (p = 0.027 and p = 0.017, respectively). Second primary malignancies were identified in 17/253 (6.4\%) and 19/263 (7.0\%) of patients treated with CD and CDP respectively. Breast (2.4\%) followed by colon (1\%) were the two cancers most frequently diagnosed in this setting. Conclusion: No significant difference between treatment arms was identified. Subgroup analysis both in the initial and current reports demonstrated a trend towards improved RFS and OS in patients treated with CDP and EFRT. This long-term analysis of outcomes also identified the necessity of providing on-going cancer screening to patients enrolled in trials.",

keywords = "Advanced endometrial cancer, Chemotherapy and radiation, Long-term follow-up, Optimal surgery",

author = "Spirtos, \{Nick M.\} and Danielle Enserro and Homesley, \{Howard D.\} and Gibbons, \{Susan K.\} and David Cella and Morris, \{Robert T.\} and Koen DeGeest and Lee, \{Roger B.\} and Miller, \{David S.\}",

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year = "2019",

month = jul,

doi = "10.1016/j.ygyno.2019.03.240",

language = "English (US)",

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T1 - The addition of paclitaxel to doxorubicin and cisplatin and volume-directed radiation does not improve overall survival (OS) or long-term recurrence-free survival (RFS) in advanced endometrial cancer (EC)

T2 - A randomized phase III NRG/Gynecologic Oncology Group (GOG) study

AU - Spirtos, Nick M.

AU - Enserro, Danielle

AU - Homesley, Howard D.

AU - Gibbons, Susan K.

AU - Cella, David

AU - Morris, Robert T.

AU - DeGeest, Koen

AU - Lee, Roger B.

AU - Miller, David S.

PY - 2019/7

Y1 - 2019/7

N2 - Objectives: To determine if the addition of paclitaxel (P) to cisplatin and doxorubicin (CD) following surgical debulking and volume-directed radiation therapy improved long-term, recurrence-free survival (RFS) and overall survival (OS) in patients with advanced-stage endometrial cancer (EC). Methods: Prospective, randomized GOG trial comparing (CD) (50 mg/m2)/(45 mg/m2) +/− (P) (160 mg/m2) following volume-directed radiation and surgery in advanced EC. A Kaplan-Meier (KM) analysis characterized the relationship between treatment arms and the OS outcome, a log-rank test assessed the independence of treatment with the OS outcome, and the treatment effect on estimated OS was determined using a Cox proportional hazards (PH) model stratified by stage. The PH assumption was assessed using a test of interaction between treatment variable and the natural logarithm of survival time. Adverse events, regardless of attribution, were graded. Results: Since initial publication, 60 deaths occurred, leaving 311 patients alive with 290 (93.8%) recurrence- free. There was no significant decrease in the risk of recurrence or death associated with the CDP treatment regimen stratified for stage (p = 0.14, one-tail). The exploratory analysis for OS and the corresponding homogeneity tests for different effects across subgroups revealed only EFRT and EFRT & GRD status to have significantly different treatment effects (p = 0.027 and p = 0.017, respectively). Second primary malignancies were identified in 17/253 (6.4%) and 19/263 (7.0%) of patients treated with CD and CDP respectively. Breast (2.4%) followed by colon (1%) were the two cancers most frequently diagnosed in this setting. Conclusion: No significant difference between treatment arms was identified. Subgroup analysis both in the initial and current reports demonstrated a trend towards improved RFS and OS in patients treated with CDP and EFRT. This long-term analysis of outcomes also identified the necessity of providing on-going cancer screening to patients enrolled in trials.

AB - Objectives: To determine if the addition of paclitaxel (P) to cisplatin and doxorubicin (CD) following surgical debulking and volume-directed radiation therapy improved long-term, recurrence-free survival (RFS) and overall survival (OS) in patients with advanced-stage endometrial cancer (EC). Methods: Prospective, randomized GOG trial comparing (CD) (50 mg/m2)/(45 mg/m2) +/− (P) (160 mg/m2) following volume-directed radiation and surgery in advanced EC. A Kaplan-Meier (KM) analysis characterized the relationship between treatment arms and the OS outcome, a log-rank test assessed the independence of treatment with the OS outcome, and the treatment effect on estimated OS was determined using a Cox proportional hazards (PH) model stratified by stage. The PH assumption was assessed using a test of interaction between treatment variable and the natural logarithm of survival time. Adverse events, regardless of attribution, were graded. Results: Since initial publication, 60 deaths occurred, leaving 311 patients alive with 290 (93.8%) recurrence- free. There was no significant decrease in the risk of recurrence or death associated with the CDP treatment regimen stratified for stage (p = 0.14, one-tail). The exploratory analysis for OS and the corresponding homogeneity tests for different effects across subgroups revealed only EFRT and EFRT & GRD status to have significantly different treatment effects (p = 0.027 and p = 0.017, respectively). Second primary malignancies were identified in 17/253 (6.4%) and 19/263 (7.0%) of patients treated with CD and CDP respectively. Breast (2.4%) followed by colon (1%) were the two cancers most frequently diagnosed in this setting. Conclusion: No significant difference between treatment arms was identified. Subgroup analysis both in the initial and current reports demonstrated a trend towards improved RFS and OS in patients treated with CDP and EFRT. This long-term analysis of outcomes also identified the necessity of providing on-going cancer screening to patients enrolled in trials.

KW - Advanced endometrial cancer

KW - Chemotherapy and radiation

KW - Long-term follow-up

KW - Optimal surgery

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The addition of paclitaxel to doxorubicin and cisplatin and volume-directed radiation does not improve overall survival (OS) or long-term recurrence-free survival (RFS) in advanced endometrial cancer (EC): A randomized phase III NRG/Gynecologic Oncology Group (GOG) study

Abstract

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