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

Research output: Contribution to journalArticle

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/m 2 )/(45 mg/m 2 ) +/− (P) (160 mg/m 2 ) 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 languageEnglish (US)
JournalGynecologic Oncology
DOIs
StatePublished - Jan 1 2019

Fingerprint

Endometrial Neoplasms
Paclitaxel
Doxorubicin
Cisplatin
Radiation
Recurrence
Survival
Cytidine Diphosphate
Arm
Therapeutics
Second Primary Neoplasms
Kaplan-Meier Estimate
Survival Analysis
Early Detection of Cancer
Proportional Hazards Models
Publications
Colon
Breast
Radiotherapy
Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

Cite this

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.; Gibbons, Susan K.; Cella, David; Morris, Robert T.; DeGeest, Koen; Lee, Roger B.; Miller, David S.

In: Gynecologic Oncology, 01.01.2019.

Research output: Contribution to journalArticle

@article{737ec8e671054d5abe89d677e2af17e0,
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/m 2 )/(45 mg/m 2 ) +/− (P) (160 mg/m 2 ) 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}",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.ygyno.2019.03.240",
language = "English (US)",
journal = "Gynecologic Oncology",
issn = "0090-8258",
publisher = "Academic Press Inc.",

}

TY - JOUR

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 - 2019/1/1

Y1 - 2019/1/1

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/m 2 )/(45 mg/m 2 ) +/− (P) (160 mg/m 2 ) 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/m 2 )/(45 mg/m 2 ) +/− (P) (160 mg/m 2 ) 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

UR - http://www.scopus.com/inward/record.url?scp=85064938672&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064938672&partnerID=8YFLogxK

U2 - 10.1016/j.ygyno.2019.03.240

DO - 10.1016/j.ygyno.2019.03.240

M3 - Article

C2 - 31053405

AN - SCOPUS:85064938672

JO - Gynecologic Oncology

JF - Gynecologic Oncology

SN - 0090-8258

ER -